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Sample records for andsevere human obesity

  1. Lack of Support for the Association Between GAD2 Polymorphisms andSevere Human Obesity

    Energy Technology Data Exchange (ETDEWEB)

    Swarbrick, Michael M.; Waldenmaier, Bjorn; Pennacchio, Len A.; Lind,Denise L.; Cavazos, Martha M.; Geller, Frank; Merriman, Raphael; Ustaszewska, Anna; Malloy, Mary; Scherag, Andre; Hsueh, Wen-Chi; Rief,Winfried; Mauvais-Jarvis, Franck; Pullinger, Clive R.; Kane, John P.; Dent, Robert; McPherson, Ruth; Kwok, Pui-Yan; Hinney, Anke; Hebebrand,Johannes; Vaisse, Christian

    2004-11-17

    Demonstration of association between common genetic variants and chronic human diseases such as obesity could have profound implications for the prediction, prevention and treatment of these conditions. Unequivocal proof of such an association, however, requires adherence to established methodological guidelines, which include independent replication of initial positive findings. Recently, single nucleotide polymorphisms (SNPs) within GAD2 were found to be associated with class III obesity (BMI > 40 kg/m2) in 188 families (612 individuals) segregating the condition and a case-control study of 575 cases and 646 lean controls. Functional data supporting a pathophysiological role for one of the SNPs (-243A>G) were also presented. In the present study, we attempted to replicate this association in larger groups of subjects, and to extend the functional studies of the -243A>G SNP. In 2,327 subjects comprising 692 German nuclear families with severe, early-onset obesity, we found no evidence for a relationship between the three GAD2 SNPs and obesity, whether SNPs were studied individually or as haplotypes. In two independent case-control studies (a total of 680 class III obesity cases and 1,186 lean controls), there was no significant relationship between the -243A>G SNP and obesity (odds ratio (OR) = 0.99, 95% CI 0.83 - 1.18,in the pooled sample). These negative findings were reinforced by a meta-analysis for the association between the 243G allele and class III obesity, which yielded an OR of 1.11 (95% CI 0.90 - 1.36) in a total sample of 1,252 class III obese cases and 1,800 lean controls. Finally,we were unable to confirm or extend the functional data pertaining to the -243A>G variant. Potential confounding variables in association studies involving common variants and complex diseases (low power to detect modest genetic effects, over-interpretation of marginal data, population stratification and biological plausibility) are also discussed in the context of GAD2 and

  2. Human adenovirus-36 and childhood obesity.

    Science.gov (United States)

    Atkinson, Richard L

    2011-09-01

    There is increasing evidence that obesity in humans is associated with infection with human adenovirus-36 (Adv36). Infection of experimental animals with Adv36 demonstrates that this virus causes obesity. Human studies have shown a prevalence of Adv36 infection of 30% or greater in obese adult humans, but a correlation with obesity has not always been demonstrated. In contrast, three published studies and one presented study with a total of 559 children all show that there is an increase in prevalence of Adv36 infection in obese children (28%) compared to non-obese children (10%). The explanation for the apparently more robust correlation of Adv36 infection with obesity in children vs. adults is not clear. The data in animals and people suggests that Adv36 has contributed to the worldwide increase in childhood obesity. More research is needed to identify prevalences and consequences of Adv36 infection in people of all age groups and geographic locations.

  3. Human obesity and endothelium-dependent responsiveness

    Science.gov (United States)

    Campia, Umberto; Tesauro, Manfredi; Cardillo, Carmine

    2012-01-01

    Obesity is an ongoing worldwide epidemic. Besides being a medical condition in itself, obesity dramatically increases the risk of development of metabolic and cardiovascular disease. This risk appears to stem from multiple abnormalities in adipose tissue function leading to a chronic inflammatory state and to dysregulation of the endocrine and paracrine actions of adipocyte-derived factors. These, in turn, disrupt vascular homeostasis by causing an imbalance between the NO pathway and the endothelin 1 system, with impaired insulin-stimulated endothelium-dependent vasodilation. Importantly, emerging evidence suggests that the vascular dysfunction of obesity is not just limited to the endothelium, but also involves the other layers of the vessel wall. In particular, obesity-related changes in medial smooth muscle cells seem to disrupt the physiological facilitatory action of insulin on the responsiveness to vasodilator stimuli, whereas the adventitia and perivascular fat appear to be a source of pro-inflammatory and vasoactive factors that may contribute to endothelial and smooth muscle cell dysfunction, and to the pathogenesis of vascular disease. While obesity-induced vascular dysfunction appears to be reversible, at least in part, with weight control strategies, these have not proved sufficient to prevent the metabolic and cardiovascular complication of obesity on a large scale. While a number of currently available drugs have shown potentially beneficial vascular effects in patients with obesity and the metabolic syndrome, elucidation of the pathophysiological mechanisms underlying vascular damage in obese patients is necessary to identify additional pharmacologic targets to prevent the cardiovascular complications of obesity, and their human and economic costs. LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3 PMID:21895631

  4. Genetic approaches to understanding human obesity

    OpenAIRE

    Ramachandrappa, Shwetha; Farooqi, I. Sadaf

    2011-01-01

    Obesity and its associated comorbidities represent one of the biggest public health challenges facing the world today. The heritability of body weight is high, and genetic variation plays a major role in determining the interindividual differences in susceptibility or resistance to the obesogenic environment. Here we discuss how genetic studies in humans have contributed to our understanding of the central ...

  5. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

    NARCIS (Netherlands)

    Hendricks, Audrey E.; Bochukova, Elena G.; Marenne, Gaëlle; Keogh, Julia M.; Atanassova, Neli; Bounds, Rebecca; Wheeler, Eleanor; Mistry, Vanisha; Henning, Elana; Körner, Antje; Muddyman, Dawn; McCarthy, Shane; Hinney, Anke; Hebebrand, Johannes; Scott, Robert A.; Langenberg, Claudia; Wareham, Nick J.; Surendran, Praveen; Howson, Joanna M M; Butterworth, Adam S.; Danesh, John; Nordestgaard, Børge G.; Nielsen, Sune F.; Afzal, Shoaib; Papadia, Sofia; Ashford, Sofie; Garg, Sumedha; Millhauser, Glenn L.; Palomino, Rafael I.; Kwasniewska, Alexandra; Tachmazidou, Ioanna; O'Rahilly, Stephen; Zeggini, Eleftheria; Barroso, Inês; Farooqi, I. Sadaf; Benzeval, Michaela; Burton, Jonathan; Buck, Nicholas; Jäckle, Annette; Kumari, Meena; Laurie, Heather; Lynn, Peter; Pudney, Stephen; Rabe, Birgitta; Wolke, Dieter; Overvad, Kim; Tjønneland, Anne; Clavel-Chapelon, Francoise; Kaaks, Rudolf; Boeing, Heiner; Trichopoulou, Antonia; Ferrari, Pietro; Palli, Domenico; Krogha, Vittorio; Panico, Salvatore; Tuminoa, Rosario; Matullo, Giuseppe; Boer, Jolanda Ma; Van Der Schouw, Yvonne; Weiderpass, Elisabete; Quiros, J. Ramon; Sánchez, María José; Navarro, Carmen; Moreno-Iribas, Conchi; Arriola, Larraitz; Melander, Olle; Wennberg, Patrik; Key, Timothy J.; Riboli, Elio; Al-Turki, Saeed; Anderson, Carl A; Anney, Richard; Antony, Dinu; Soler Artigas, María; Ayub, Muhammad; Bala, Senduran; Barrett, Jeffrey C; Beales, Phil; Bentham, Jamie; Bhattacharyaa, Shoumo; Birney, Ewan; Blackwooda, Douglas; Bobrow, Martin; Bolton, Patrick F.; Boustred, Chris; Breen, Gerome; Calissanoa, Mattia; Carss, Keren; Charlton, Ruth; Chatterjee, Krishna; Chen, Lu; Ciampia, Antonio; Cirak, Sebahattin; Clapham, Peter; Clement, Gail; Coates, Guy; Coccaa, Massimiliano; Collier, David A; Cosgrove, Catherine; Coxa, Tony; Craddock, Nick; Crooks, Lucy; Curran, Sarah; Curtis, David; Daly, Allan; Danecek, Petr; Day, Ian N M; Day-Williams, Aaron G; Dominiczak, Anna; Down, Thomas; Du, Yuanping; Dunham, Ian; Durbin, Richard; Edkins, Sarah; Ekong, Rosemary; Ellis, Peter; Evansa, David M.; FitzPatrick, David R.; Flicek, Paul; Floyd, James S.; Foley, A. Reghan; Franklin, Christopher S.; Futema, Marta; Gallagher, Louise; Gaunt, Tom R.; Geihs, Matthias; Geschwind, Daniel H.; Greenwood, Celia M.T.; Griffin, Heather; Grozeva, Detelina; Guo, Xiaosen; Guo, Xueqin; Gurling, Hugh; Hart, Deborah J.; Holmans, Peter A; Howie, Bryan; Huang, Jie; Huang, Liren; Hubbard, Tim; Humphries, Steve E.; Hurles, Matthew E.; Hysi, Pirro G.; Iotchkova, Valentina; Jackson, David K.; Jamshidi, Yalda; Joyce, Chris; Karczewski, Konrad J.; Kaye, Jane; Keane, Thomas; Kemp, John P.; Kennedy, Karen; Kent, Alastair; Khawaja, Farrah; Van Kogelenberg, Margriet; Kolb-Kokocinski, Anja; Lachance, Genevieve; Langford, Cordelia; Lawson, Daniel; Lee, Irene; Lek, Monkol; Li, Rui; Li, Yingrui; Liang, Jieqin; Lin, Hong; Liu, Ryan; Lönnqvist, Jouko; Lopes, Luis R.; Lopes, Margarida; MacArthur, Daniel G.; Mangino, Massimo; Marchini, Jonathan; Maslen, John; Mathieson, Iain; McGuffin, Peter; McIntosh, Andrew M.; McKechanie, Andrew G.; McQuillin, Andrew; Memari, Yasin; Metrustry, Sarah; Migone, Nicola; Min, Josine L.; Mitchison, Hannah M; Moayyeri, Alireza; Morris, Andrew D.; Morris, James; Muntoni, Francesco; Northstone, Kate; O'Donovan, Michael C.; Onoufriadis, Alexandros; Oualkacha, Karim; Owen, Michael J; Palotie, Aarno; Panoutsopoulou, Kalliope; Parker, Victoria; Parr, Jeremy R.; Paternoster, Lavinia; Paunio, Tiina; Payne, Felicity; Payne, Stewart J.; Perry, John R. B.; Pietilainen, Olli; Plagnol, Vincent; Pollitt, Rebecca C.; Porteous, David J.; Povey, Sue; Quail, Michael A.; Quaye, Lydia; Raymond, F. Lucy; Rehnström, Karola; Richards, J Brent; Ridout, Cheryl K.; Ring, Susan M.; Ritchie, Graham R.S.; Roberts, Nicola; Robinson, Rachel L.; Savage, David B.; Scambler, Peter; Schiffels, Stephan; Schmidts, Miriam; Schoenmakers, Nadia; Scott, Richard H.; Semple, Robert K.; Serra, Eva; Sharp, Sally I.; Shaw, Adam; Shihab, Hashem A.; Shin, So Youn; Skuse, David; Small, Kerrin S; Smee, Carol; Smith, Blair H.; Davey Smith, George; Soranzo, Nicole; Southam, Lorraine; Spasic-Boskovic, Olivera; Spector, Timothy D; St Clair, David; St Pourcain, Beate; Stalker, Jim; Stevens, Elizabeth; Sun, Jianping; Surdulescu, Gabriela L; Suvisaari, Jaana; Syrris, Petros; Taylor, Rohan; Tian, Jing; Timpson, Nicholas J.; Tobin, Martin D; Valdes, Ana M.; Vandersteen, Anthony M.; Vijayarangakannan, Parthiban; Visscher, Peter M.; Wain, Louise V.; Walter, Klaudia; Walters, James T.R.; Wang, Guangbiao; Wang, Jun; Wang, Nai-Yu; Ward, Kirsten; Whyte, Tamieka; Williams, Hywel J.; Williamson, Kathleen A.; Wilson, Crispian; Wilson, Scott G.; Wong, Kim; Xu, Changjiang; Yang, Jian; Zhang, Feng; Zhang, Pingbo; Zheng, Hou Feng

    2017-01-01

    Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS,

  6. Hunter-gatherer energetics and human obesity.

    Directory of Open Access Journals (Sweden)

    Herman Pontzer

    Full Text Available Western lifestyles differ markedly from those of our hunter-gatherer ancestors, and these differences in diet and activity level are often implicated in the global obesity pandemic. However, few physiological data for hunter-gatherer populations are available to test these models of obesity. In this study, we used the doubly-labeled water method to measure total daily energy expenditure (kCal/day in Hadza hunter-gatherers to test whether foragers expend more energy each day than their Western counterparts. As expected, physical activity level, PAL, was greater among Hadza foragers than among Westerners. Nonetheless, average daily energy expenditure of traditional Hadza foragers was no different than that of Westerners after controlling for body size. The metabolic cost of walking (kcal kg(-1 m(-1 and resting (kcal kg(-1 s(-1 were also similar among Hadza and Western groups. The similarity in metabolic rates across a broad range of cultures challenges current models of obesity suggesting that Western lifestyles lead to decreased energy expenditure. We hypothesize that human daily energy expenditure may be an evolved physiological trait largely independent of cultural differences.

  7. Obesity accelerates epigenetic aging of human liver.

    Science.gov (United States)

    Horvath, Steve; Erhart, Wiebke; Brosch, Mario; Ammerpohl, Ole; von Schönfels, Witigo; Ahrens, Markus; Heits, Nils; Bell, Jordana T; Tsai, Pei-Chien; Spector, Tim D; Deloukas, Panos; Siebert, Reiner; Sipos, Bence; Becker, Thomas; Röcken, Christoph; Schafmayer, Clemens; Hampe, Jochen

    2014-10-28

    Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an "epigenetic clock") to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10(-4) in dataset 1 and r = 0.42, P = 1.2 × 10(-4) in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10(-9)) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer.

  8. Mutation analysis of the MCHR1 gene in human obesity

    DEFF Research Database (Denmark)

    Wermter, Anne-Kathrin; Reichwald, Kathrin; Büch, Thomas

    2005-01-01

    The importance of the melanin-concentrating hormone (MCH) system for regulation of energy homeostasis and body weight has been demonstrated in rodents. We analysed the human MCH receptor 1 gene (MCHR1) with respect to human obesity....

  9. Genetic approaches to understanding human obesity.

    Science.gov (United States)

    Ramachandrappa, Shwetha; Farooqi, I Sadaf

    2011-06-01

    Obesity and its associated comorbidities represent one of the biggest public health challenges facing the world today. The heritability of body weight is high, and genetic variation plays a major role in determining the interindividual differences in susceptibility or resistance to the obesogenic environment. Here we discuss how genetic studies in humans have contributed to our understanding of the central pathways that govern energy homeostasis. We discuss how the arrival of technological advances such as next-generation sequencing will result in a major acceleration in the pace of gene discovery. The study of patients harboring these genetic variants has informed our understanding of the molecular and physiological pathways involved in energy homeostasis. We anticipate that future studies will provide the framework for the development of a more rational targeted approach to the prevention and treatment of genetically susceptible individuals.

  10. Medical Implications of Obesity in Horses—Lessons for Human Obesity

    Science.gov (United States)

    Johnson, Philip J.; Wiedmeyer, Charles E.; Messer, Nat T.; Ganjam, Venkataseshu K.

    2009-01-01

    There is growing recognition that obesity is common and represents a significant detriment to the health of companion animals in a manner similar to that by which it is affecting the human population. As is the case for other species, obesity appears to promote insulin resistance in horses and it is through this pathophysiological process that many of the adverse medical consequences of obesity are being characterized. Equine medical conditions that have been described in the context of obesity and insulin resistance differ from those in humans. Chronic human conditions that have been attributed to obesity and insulin resistance, such as atherosclerosis and diabetes mellitus, are rarely described in obese horses. Significant current interest is centered on the recognition that insulin resistance plays a role in the pathogenesis of laminitis, a potentially severe and debilitating cause of lameness in the equine species. Other equine medical conditions that are more likely in obese, insulin-resistant individuals include hyperlipemia (hepatic lipidosis) and developmental orthopedic disease (osteochondrosis). Pituitary pars intermedia dysfunction (equine Cushing's syndrome) represents another common endocrinopathic condition of older horses associated with insulin resistance. This review presents an introductory overview of the present understanding of obesity and insulin resistance and how these conditions may be associated with disease conditions in horses. PMID:20046661

  11. Effects of Probiotics on Human Obesity Control: An Unproven Hypothesis

    Directory of Open Access Journals (Sweden)

    Amparo Arias

    2014-01-01

    Full Text Available The objective of the present study is to review the different publications associated with probiotics and obesity, as well as to get some new insights regarding the role of the microbiome in diseases such as obesity. An extensive search for scientific publications (studies in animal models, cells, clinical trials and reviews was performed in the following specialist computer databases (PubMed central (PMC-NCBI, Elsevier Journal, Scielo Spain, Scirus, Science Direct to establish the current status of the potential effect of probiotics in the control of obesity in humans, as well as the relationship between intestinal microbiota and obesity. The intestinal microbiota and oral probiotics have a positive effect on human health, as they can regulate the immune functions and protect from infections and chronic inflammatory processes. Although divergent results have recently been reported, it has been shown but not confirmed that intestinal microbiota might play a role as a new factor associated with the regulation of body weight and obesity-related diseases. The international MetaHIT project has shown that human microbiome populations can be grouped into three different enterotypes. Two of these enterotypes (Bacteroides and Ruminococcus seem to encode functions related to obesity. Although the relationship between intestinal microbiota and obesity are not yet well established, the attempt to manipulate intestinal microbiota through diet is suggested as a new plausible approach to prevent, or modify the risk of, obesity and its related diseases.

  12. Unraveling the genetics of human obesity.

    Directory of Open Access Journals (Sweden)

    David M Mutch

    2006-12-01

    Full Text Available The use of modern molecular biology tools in deciphering the perturbed biochemistry and physiology underlying the obese state has proven invaluable. Identifying the hypothalamic leptin/melanocortin pathway as critical in many cases of monogenic obesity has permitted targeted, hypothesis-driven experiments to be performed, and has implicated new candidates as causative for previously uncharacterized clinical cases of obesity. Meanwhile, the effects of mutations in the melanocortin-4 receptor gene, for which the obese phenotype varies in the degree of severity among individuals, are now thought to be influenced by one's environmental surroundings. Molecular approaches have revealed that syndromes (Prader-Willi and Bardet-Biedl previously assumed to be controlled by a single gene are, conversely, regulated by multiple elements. Finally, the application of comprehensive profiling technologies coupled with creative statistical analyses has revealed that interactions between genetic and environmental factors are responsible for the common obesity currently challenging many Westernized societies. As such, an improved understanding of the different "types" of obesity not only permits the development of potential therapies, but also proposes novel and often unexpected directions in deciphering the dysfunctional state of obesity.

  13. Is it acceptable to use animals to model obese humans?

    DEFF Research Database (Denmark)

    Lund, Thomas Bøker; Sørensen, Thorkild I.A.; Olsson, I. Anna S.

    2014-01-01

    for the view that this form of animal use, unlike some other forms of animal-based medical research, cannot be defended. The first argument leans heavily on the notion that people themselves are responsible for developing obesity and so-called 'lifestyle' diseases; the second involves the claim that animal......Animal use in medical research is widely accepted on the basis that it may help to save human lives and improve their quality of life. Recently, however, objections have been made specifically to the use of animals in scientific investigation of human obesity. This paper discusses two arguments...... of animals in obesity research as especially problematic....

  14. Molecular genetics of human obesity: A comprehensive review.

    Science.gov (United States)

    Singh, Rajan Kumar; Kumar, Permendra; Mahalingam, Kulandaivelu

    2017-02-01

    Obesity and its related health complications is a major problem worldwide. Hypothalamus and their signalling molecules play a critical role in the intervening and coordination with energy balance and homeostasis. Genetic factors play a crucial role in determining an individual's predisposition to the weight gain and being obese. In the past few years, several genetic variants were identified as monogenic forms of human obesity having success over common polygenic forms. In the context of molecular genetics, genome-wide association studies (GWAS) approach and their findings signified a number of genetic variants predisposing to obesity. However, the last couple of years, it has also been noticed that alterations in the environmental and epigenetic factors are one of the key causes of obesity. Hence, this review might be helpful in the current scenario of molecular genetics of human obesity, obesity-related health complications (ORHC), and energy homeostasis. Future work based on the clinical discoveries may play a role in the molecular dissection of genetic approaches to find more obesity-susceptible gene loci. Copyright © 2016 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

  15. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

    DEFF Research Database (Denmark)

    Hendricks, Audrey E; Bochukova, Elena G; Marenne, Gaëlle

    2017-01-01

    Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS.......1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10-3), highlighting...... the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do...

  16. Effects of obesity on human sexual development.

    Science.gov (United States)

    Wagner, Isabel V; Sabin, Mathew A; Pfäffle, Roland W; Hiemisch, Andreas; Sergeyev, Elena; Körner, Antje; Kiess, Wieland

    2012-01-31

    Puberty is a period of physical and psychological maturation, with long-term effects on health. During the 20(th) century, a secular trend towards earlier puberty occurred in association with improvements in nutrition. The worldwide pandemic of childhood obesity has renewed interest in the relationship between body composition in childhood and the timing and tempo of puberty. Limited evidence suggests that earlier puberty is associated with a tendency towards central fat deposition; therefore, pubertal status needs to be carefully considered in the categorization of childhood and adolescent overweight and obesity. In the other direction, rapid early weight gain is associated with advanced puberty in both sexes, and a clear association exists between increasing BMI and earlier pubertal development in girls. Evidence in boys is less clear, with the majority of studies showing obesity to be associated with earlier puberty and voice break, although a subgroup of boys with obesity exhibits late puberty, perhaps as a variation of constitutional delay in growth and puberty. The possible mechanisms linking adiposity with pubertal timing are numerous, but leptin, adipocytokines and gut peptides are central players. Other possible mediators include genetic variation and environmental factors such as endocrine disrupting chemicals. This Review presents current evidence on this topic, highlighting inconsistencies and opportunities for future research.

  17. Obesity induction in hamster that mimics the human clinical condition.

    Science.gov (United States)

    Jordania da Silva, Vivian; Dias, Sílvia Regina Costa; Maioli, Tatiani Uceli; Serafim, Luciana Ribeiro; Furtado, Luis Fernando Viana; Quintão Silva, Maria da Gloria; Faria, Ana Maria Caetano de; Rabelo, Élida Mara Leite

    2017-08-05

    Although obesity is well established in hamsters, studies using diets with high levels of simple carbohydrate associated with lipids are necessary to assess the impact of this type of food in the body. In this study a high sugar and butter diet (HSB) and high temperature were employed towards this end. Obesity was successfully induced at a temperature of 30.3°C to 30.9°C after 38 days feeding the animals an HSB diet. It was shown that although diet is important for the induction of obesity, temperature is also essential because at a temperature slightly below the one required, obesity was not induced, even when the animals were fed for a longer period (150 days).The obese clinical condition was accompanied by biochemical and hematological changes, as increased cholesterol and triglyceride levels and increased leukocyte numbers, similar to alterations observed in obese humans. Furthermore, it was demonstrated that increasing the intake of simple carbohydrates associated with lipids provided evidence of inflammation in obese animals.

  18. The Cat as a Model for Human Obesity and Diabetes

    Science.gov (United States)

    Hoenig, Margarethe

    2012-01-01

    Obesity is the most common nutritional disorder of cats and is a risk factor for diabetes. Similar to developments in obese people, obese cats show peripheral tissue insulin resistance and may demonstrate glucose intolerance when challenged with pharmacological amounts of glucose. However, they compensate well for the insulin resistance and do not show elevated glucose concentrations when monitored during their regular daily routine, including postprandial periods. This is possible because obese cats in the fasted and postprandial state are able to maintain hepatic insulin sensitivity and decrease endogenous glucose production, which allows them to maintain normoglycemia. Also dissimilar to what is seen in many obese humans, cats do not develop atherosclerosis and clinical hypertension. The time course for progression to overt diabetes of obese cats is unknown. One might speculate that diabetes develops when the liver finally becomes insulin resistant and/or insulin secretion becomes too low to overcome increased glucose production. In addition, amyloid, demonstrated to be deposited in islet of chronically obese cats, may contribute to a reduction in insulin secretion by reducing functional β-cell mass. PMID:22768882

  19. Elevated Serum Level of Human Alkaline Phosphatase in Obesity

    International Nuclear Information System (INIS)

    Khan, A. R.; Awan, F. R.; Najam, S. S.; Islam, M.; Siddique, T.; Zain, M.

    2015-01-01

    Objective: To investigate a correlation between serum alkaline phosphatase level and body mass index in human subjects. Methods: The comparative cross-sectional study was carried out at the National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan, from April 2012 to June 2013. Blood serum alkaline phosphatase levels were estimated and the subjects were divided into three sub-groups on the basis of their body mass index: normal weight (<25kg/m2), overweight (25-27kg/m2) and obese (>27kg/m2) subjects. The serum samples were used for the estimation of clinically important biochemical parameters, using commercial kits on clinical chemistry analyser. Results: Of the 197 subjects, 97(49 percent) were obese and 100(51 percent) were non-obese. The serum alkaline phosphatase level increased in obese (214±6.4 IU/L) compared to the non-obese subjects (184.5±5 IU/L). Furthermore, a significant linear relationship (r=0.3;p-0.0001) was found between serum alkaline phosphatase and body mass index. Other biochemical variables were not correlated to the body mass index. Conclusion: Over activity and higher amounts of alkaline phosphatase were linked to the development of obesity. (author)

  20. Similar Adiponectin Levels in Obese Normotensive and Obese Hypertensive Men and No Vasorelaxant Effect of Adiponectin on Human Arteries

    DEFF Research Database (Denmark)

    Dreier, Rasmus; Asferg, Camilla; Berg, Jais O

    2016-01-01

    /80 mmHg (ObeseHT) and 40 had 24-hr ABP ObeseNT). As controls, we studied 27 men with BMI between 20.0 and 24.9 kg/m(2) and 24-hr ABP .... In conclusion, obese hypertensive men have similar serum concentrations of adiponectin as obese normotensive men. In combination with the in vitro data, these findings question a pathogenic role of adiponectin in human hypertension.......Obesity is a strong risk factor for hypertension, but the mechanism linking obesity to hypertension is not fully elucidated. In obesity, circulating concentrations of adiponectin are decreased and hypoadiponectinaemia has in some but not all studies been associated with increased risk...

  1. Social sciences and humanities contribution to tackle the obesity epidemic

    DEFF Research Database (Denmark)

    Holm, Lotte; Sandøe, Peter; Nielsen, Morten Ebbe Juul

    To address the obesity epidemic, European researchers need to come together to find the best solutions and use their combined knowledge to provide the most innovative research ideas. By gathering more than 50 researchers and stakeholders from around Europe, we took an important step towards...... establishing strong networks and building bridges between the natural sciences and social sciences and humanities that can address obesity as a complex societal challenge and help minimise the gap between research, markets, and citizens. The objectives of the workshop were to create a cross‐European forum...

  2. Endocannabinoids measurement in human saliva as potential biomarker of obesity.

    Science.gov (United States)

    Matias, Isabelle; Gatta-Cherifi, Blandine; Tabarin, Antoine; Clark, Samantha; Leste-Lasserre, Thierry; Marsicano, Giovanni; Piazza, Pier Vincenzo; Cota, Daniela

    2012-01-01

    The discovery of the endocannabinoid system and of its role in the regulation of energy balance has significantly advanced our understanding of the physiopathological mechanisms leading to obesity and type 2 diabetes. New knowledge on the role of this system in humans has been acquired by measuring blood endocannabinoids. Here we explored endocannabinoids and related N-acylethanolamines in saliva and verified their changes in relation to body weight status and in response to a meal or to body weight loss. Fasting plasma and salivary endocannabinoids and N-acylethanolamines were measured through liquid mass spectrometry in 12 normal weight and 12 obese, insulin-resistant subjects. Salivary endocannabinoids and N-acylethanolamines were evaluated in the same cohort before and after the consumption of a meal. Changes in salivary endocannabinoids and N-acylethanolamines after body weight loss were investigated in a second group of 12 obese subjects following a 12-weeks lifestyle intervention program. The levels of mRNAs coding for enzymes regulating the metabolism of endocannabinoids, N-acylethanolamines and of cannabinoid type 1 (CB(1)) receptor, alongside endocannabinoids and N-acylethanolamines content, were assessed in human salivary glands. The endocannabinoids 2-arachidonoylglycerol (2-AG), N-arachidonoylethanolamide (anandamide, AEA), and the N-acylethanolamines (oleoylethanolamide, OEA and palmitoylethanolamide, PEA) were quantifiable in saliva and their levels were significantly higher in obese than in normal weight subjects. Fasting salivary AEA and OEA directly correlated with BMI, waist circumference and fasting insulin. Salivary endocannabinoids and N-acylethanolamines did not change in response to a meal. CB(1) receptors, ligands and enzymes were expressed in the salivary glands. Finally, a body weight loss of 5.3% obtained after a 12-weeks lifestyle program significantly decreased salivary AEA levels. Endocannabinoids and N-acylethanolamines are

  3. Elevated serum level of human alkaline phosphatase in obesity.

    Science.gov (United States)

    Khan, Abdul Rehman; Awan, Fazli Rabbi; Najam, Syeda Sadia; Islam, Mehboob; Siddique, Tehmina; Zain, Maryam

    2015-11-01

    To investigate a correlation between serum alkaline phosphatase level and body mass index in human subjects. The comparative cross-sectional study was carried out at the National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan, from April 2012 to June 2013. Blood serum alkaline phosphatase levels were estimated and the subjects were divided into three sub-groups on the basis of their body mass. normal weight (27kg/m2) subjects. The serum samples were used for the estimation of clinically important biochemical parameters, using commercial kits on clinical chemistry analyser. Of the 197 subjects, 97(49%) were obese and 100(51%) were non-obese. The serum alkaline phosphatase level increased in obese (214±6.4 IU/L) compared to the non-obese subjects (184.5±5 IU/L). Furthermore, a significant linear relationship (r=0.3;p-0.0001) was found between serum alkaline phosphatase and body mass index. Other biochemical variables were not correlated to the body mass index. Over activity and higher amounts of alkaline phosphatase were linked to the development of obesity.

  4. Current status of the human obesity gene map.

    Science.gov (United States)

    Bouchard, C; Pérusse, L

    1996-01-01

    An overview of the status of the human obestiy gene map up to October 1995 is presented. The evidence is drawn from several lines of clinical and experimental research. First, 12 loci linked to Mendelian disorders exhibiting obesity as one clinical feature are reviewed. Second, six loci causing obesity in rodent models of the disease are considered. Third, eight chromosomal regions where quantitative trait loci, identified by crossbreeding experiments with informative strains of mice, are defined. Fourth, 10 candidate genes exhibiting a statistical association with BMI or body fat are introduced. Fifth, nine loci found to be linked to a relevant phenotype are listed and the four cases for which the evidence for linkage is strongest are emphasized. The latter are mapped to 2p25, 6p21.3, 7q33 and 20q12-13.11. Finally, the studies that have concluded that there was no association or linkage with a marker or gene are also reviewed. It is recommended that a system be developed by the obesity research community to ensure that an accurate and easily accessible computerized version of the human obesity gene map becomes available in the near future.

  5. A PYY Q62P variant linked to human obesity

    Energy Technology Data Exchange (ETDEWEB)

    Ahituv, Nadav; Kavaslar, Nihan; Schackwitz, Wendy; Ustaszewska,Anna; Collier, John Michael; Hebert, Sybil; Doelle, Heather; Dent,Robert; Pennacchio, Len A.; McPherson, Ruth

    2005-06-27

    Members of the pancreatic polypeptide family and the irreceptors have been implicated in the control of food intake in rodents and humans. To investigate whether nucleotide changes in these candidate genes result in abnormal weight in humans, we sequenced the coding exons and splice sites of seven family members (NPY, PYY, PPY, NPY1R, NPY2R, NPY4R, and NPY5R) in a large cohort of extremely obese (n=379) and lean (n=378) individuals. In total we found eleven rare non-synonymous variants, four of which exhibited familial segregation, NPY1R L53P and PPY P63L with leanness and NPY2R D42G and PYY Q62P with obesity. Functional analysis of the obese variants revealed NPY2R D42G to have reduced cell surface expression, while previous cell culture based studies indicated variant PYY Q62P to have altered receptor binding selectivity and we show that it fails to reduce food intake through mouse peptide injection experiments. These results support that rare non-synonymous variants within these genes can alter susceptibility to human body mass index extremes.

  6. Human Adenovirus 36 Infection Increased the Risk of Obesity

    Science.gov (United States)

    Xu, Mei-Yan; Cao, Bing; Wang, Dong-Fang; Guo, Jing-Hui; Chen, Kai-Li; Shi, Mai; Yin, Jian; Lu, Qing-Bin

    2015-01-01

    Abstract Human adenovirus 36 (HAdV-36), as the key pathogen, was supposed and discussed to be associated with obesity. We searched the references on the association between HAdV-36 infection and obesity with the different epidemiological methods, to explore the relationship with a larger sample size by meta-analysis and compare the differences of epidemiological methods and population subsets by the subgroup analyses. We conducted literature search on the association between HAdV-36 infections and obesity in English or Chinese published up to July 1, 2015. The primary outcome was the HAdV-36 infection rate in the obese and lean groups; the secondary outcomes were the BMI level and BMI z-score in the HAdV-36 positive and negative groups. The pooled odds ratio (OR) was calculated for the primary outcome; the standardized mean differences (SMDs) were calculated for the secondary and third outcomes. Prediction interval (PI) was graphically presented in the forest plot of the random effect meta-analyses. Metaregression analysis and subgroup analysis were performed. Finally 24 references with 10,191 study subjects were included in the meta-analysis. The obesity subjects were more likely to be infected with HAdV-36 compared to the lean controls (OR = 2.00; 95%CI: 1.46, 2.74; PI: 0.59, 6.76; P infection for obesity were 1.77 (95%CI: 1.19, 2.63; PI: 0.44, 7.03; P = 0.005) and 2.26 (95%CI: 1.67, 3.07; PI: 1.45, 3.54; P SMD of BMI was 0.28 (95% CI: 0.08, 0.47; PI: −0.53, 1.08; P = 0.006) in the HAdV-36 positive subjects with a high heterogeneity (I2 = 86.5%; P infection was higher than those without HAdV-36 infection (SMD = 0.19; 95%CI: −0.31, 0.70; PI: −2.10, 2.49), which had no significantly statistical difference (P = 0.453). HAdV-36 infection increased the risk of obesity. HAdV-36 also increased the risk of weight gain in adults, which was not observed in children. PMID:26705235

  7. Endocannabinoids Measurement in Human Saliva as Potential Biomarker of Obesity

    Science.gov (United States)

    Tabarin, Antoine; Clark, Samantha; Leste-Lasserre, Thierry; Marsicano, Giovanni; Piazza, Pier Vincenzo; Cota, Daniela

    2012-01-01

    Background The discovery of the endocannabinoid system and of its role in the regulation of energy balance has significantly advanced our understanding of the physiopathological mechanisms leading to obesity and type 2 diabetes. New knowledge on the role of this system in humans has been acquired by measuring blood endocannabinoids. Here we explored endocannabinoids and related N-acylethanolamines in saliva and verified their changes in relation to body weight status and in response to a meal or to body weight loss. Methodology/Principal Findings Fasting plasma and salivary endocannabinoids and N-acylethanolamines were measured through liquid mass spectrometry in 12 normal weight and 12 obese, insulin-resistant subjects. Salivary endocannabinoids and N-acylethanolamines were evaluated in the same cohort before and after the consumption of a meal. Changes in salivary endocannabinoids and N-acylethanolamines after body weight loss were investigated in a second group of 12 obese subjects following a 12-weeks lifestyle intervention program. The levels of mRNAs coding for enzymes regulating the metabolism of endocannabinoids, N-acylethanolamines and of cannabinoid type 1 (CB1) receptor, alongside endocannabinoids and N-acylethanolamines content, were assessed in human salivary glands. The endocannabinoids 2-arachidonoylglycerol (2-AG), N-arachidonoylethanolamide (anandamide, AEA), and the N-acylethanolamines (oleoylethanolamide, OEA and palmitoylethanolamide, PEA) were quantifiable in saliva and their levels were significantly higher in obese than in normal weight subjects. Fasting salivary AEA and OEA directly correlated with BMI, waist circumference and fasting insulin. Salivary endocannabinoids and N-acylethanolamines did not change in response to a meal. CB1 receptors, ligands and enzymes were expressed in the salivary glands. Finally, a body weight loss of 5.3% obtained after a 12-weeks lifestyle program significantly decreased salivary AEA levels. Conclusions

  8. Mapping and annotating obesity-related genes in pig and human genomes.

    Science.gov (United States)

    Martelli, Pier Luigi; Fontanesi, Luca; Piovesan, Damiano; Fariselli, Piero; Casadio, Rita

    2014-01-01

    Background. Obesity is a major health problem in both developed and emerging countries. Obesity is a complex disease whose etiology involves genetic factors in strong interplay with environmental determinants and lifestyle. The discovery of genetic factors and biological pathways underlying human obesity is hampered by the difficulty in controlling the genetic background of human cohorts. Animal models are then necessary to further dissect the genetics of obesity. Pig has emerged as one of the most attractive models, because of the similarity with humans in the mechanisms regulating the fat deposition. Results. We collected the genes related to obesity in humans and to fat deposition traits in pig. We localized them on both human and pig genomes, building a map useful to interpret comparative studies on obesity. We characterized the collected genes structurally and functionally with BAR+ and mapped them on KEGG pathways and on STRING protein interaction network. Conclusions. The collected set consists of 361 obesity related genes in human and pig genomes. All genes were mapped on the human genome, and 54 could not be localized on the pig genome (release 2012). Only for 3 human genes there is no counterpart in pig, confirming that this animal is a good model for human obesity studies. Obesity related genes are mostly involved in regulation and signaling processes/pathways and relevant connection emerges between obesity-related genes and diseases such as cancer and infectious diseases.

  9. Gender discrimination, gender disparities in obesity and human development.

    Science.gov (United States)

    Ferretti, Fabrizio; Mariani, Michele

    2017-03-01

    Measuring gender inequality and women's empowerment is essential to understand the determinants of gender gaps, evaluate policies and monitor countries' progress. With this aim, over the past two decades, research has mainly been directed towards the development of composite indices. The purpose of this paper is to introduce a new and interdisciplinary perspective to the current debate on measuring gender inequality in human development. As a starting point, we develop a simple macroeconomic model of the interdependence between human development and gender inequality. We then introduce a biometric indicator, based on the ratio of female to male body mass index, to measure women's empowerment at the country level. Finally, by using the latest available data, we examine the ability of this biometric indicator to capture countries' performance in achieving gender equality. We obtain five main results: 1) we provide a theoretical framework to explain the joint determination of human development and gender inequality; 2) we show how to use this framework to simulate the impact of exogenous shocks or policy changes; 3) we demonstrate that exogenous changes have a direct and a multiplier effect on human development and gender inequality; 4) we find that the distribution of obesity between the female and male populations represents a useful proxy variable for measuring gender equality at the country level; 5) finally, we use these results to integrate and develop existing knowledge on the 'ecological' approach to the overweight and obesity pandemic.

  10. Gender discrimination, gender disparities in obesity and human development

    Directory of Open Access Journals (Sweden)

    Fabrizio Ferretti

    2017-03-01

    Full Text Available Measuring gender inequality and women’s empowerment is essential to understand the determinants of gender gaps, evaluate policies and monitor countries’ progress. With this aim, over the past two decades, research has mainly been directed towards the development of composite indices. The purpose of this paper is to introduce a new and interdisciplinary perspective to the current debate on measuring gender inequality in human development. As a starting point, we develop a simple macroeconomic model of the interdependence between human development and gender inequality. We then introduce a biometric indicator, based on the ratio of female to male body mass index, to measure women’s empowerment at the country level. Finally, by using the latest available data, we examine the ability of this biometric indicator to capture countries’ performance in achieving gender equality. We obtain five main results: 1 we provide a theoretical framework to explain the joint determination of human development and gender inequality; 2 we show how to use this framework to simulate the impact of exogenous shocks or policy changes; 3 we demonstrate that exogenous changes have a direct and a multiplier effect on human development and gender inequality; 4 we find that the distribution of obesity between the female and male populations represents a useful proxy variable for measuring gender equality at the country level; 5 finally, we use these results to integrate and develop existing knowledge on the ‘ecological’ approach to the overweight and obesity pandemic.

  11. Obesity and human biology: toward a global perspective.

    Science.gov (United States)

    Brewis, Alexandra A

    2012-01-01

    Overweight bodies will soon be the modal human form. In this special issue of American Journal of Human Biology, authors use varied approaches to examine the expansion of obesity globally, particularly what shape variability in people's vulnerability to weight gain and its negative effects. The contributions together highlight how complex pathways between biology and health related to excess weight are strongly medicated, at multiple levels, by both socio-ecological context and life history. A systems approach, which can place human biological and biocultural variation iteratively within the broader contexts of developing and globalizing adiposity, will be a useful next step to informing effective prevention and intervention efforts. Copyright © 2012 Wiley Periodicals, Inc.

  12. Obese fathers lead to an altered metabolism and obesity in their children in adulthood: review of experimental and human studies

    Directory of Open Access Journals (Sweden)

    Fernanda Ornellas

    Full Text Available Abstract Objective: To discuss the recent literature on paternal obesity, focusing on the possible mechanisms of transmission of the phenotypes from the father to the children. Sources: A non-systematic review in the PubMed database found few publications in which paternal obesity was implicated in the adverse transmission of characteristics to offspring. Specific articles on epigenetics were also evaluated. As the subject is recent and still controversial, all articles were considered regardless of year of publication. Summary of findings: Studies in humans and animals have established that paternal obesity impairs their hormones, metabolism, and sperm function, which can be transmitted to their offspring. In humans, paternal obesity results in insulin resistance/type 2 diabetes and increased levels of cortisol in umbilical cord blood, which increases the risk factors for cardiovascular disease. Notably, there is an association between body fat in parents and the prevalence of obesity in their daughters. In animals, paternal obesity led to offspring alterations on glucose-insulin homeostasis, hepatic lipogenesis, hypothalamus/feeding behavior, kidney of the offspring; it also impairs the reproductive potential of male offspring with sperm oxidative stress and mitochondrial dysfunction. An explanation for these observations (human and animal is epigenetics, considered the primary tool for the transmission of phenotypes from the father to offspring, such as DNA methylation, histone modifications, and non-coding RNA. Conclusions: Paternal obesity can induce programmed phenotypes in offspring through epigenetics. Therefore, it can be considered a public health problem, affecting the children's future life.

  13. An F2 pig resource population as a model for genetic studies of obesity and obesity-related diseases in humans

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Kadarmideen, Haja; Mark, Thomas

    2013-01-01

    Obesity is a rising worldwide public health problem. Difficulties to precisely measure various obesity traits and the genetic heterogeneity in human have been major impediments to completely disentangle genetic factors causing obesity. The pig is a relevant model for studying human obesity...... and obesity-related (OOR) traits. Using founder breeds divergent with respect to obesity traits we have created an F2 pig resource population (454 pigs), which has been intensively phenotyped for 36 OOR traits. The main rationale for our study is to characterize the genetic architecture of OOR traits in the F...

  14. Obesity

    Science.gov (United States)

    Obesity means having too much body fat. It is different from being overweight, which means weighing too ... what's considered healthy for his or her height. Obesity happens over time when you eat more calories ...

  15. in obesity – an overview of human studies

    Directory of Open Access Journals (Sweden)

    A Leońska-Duniec

    2016-05-01

    Full Text Available Frequent and regular physical activity has significant benefits for health, including improvement of body composition and help in weight control. Consequently, promoting training programmes, particularly in those who are genetically predisposed, is a significant step towards controlling the presently increasing epidemic of obesity. Although the physiological responses of the human body to exercise are quite well described, the genetic background of these reactions still remains mostly unknown. This review not only summarizes the current evidence, through a literature review and the results of our studies on the influence of gene variants on the characteristics and range of the body’s adaptive response to training, but also explores research organization problems, future trends, and possibilities. We describe the most reliable candidate genetic markers that are involved in energy balance pathways and body composition changes in response to training programmes, such as FTO, MC4R, ACE, PPARG, LEP, LEPR, ADRB2, and ADRB3. This knowledge can have an enormous impact not only on individualization of exercise programmes to make them more efficient and safer, but also on improved recovery, traumatology, medical care, diet, supplementation and many other areas. Nevertheless, the current studies still represent only the first steps towards a better understanding of the genetic factors that influence obesity-related traits, as well as gene variant x physical activity interactions, so further research is necessary.

  16. Using a Human Ecosystems Approach to the Obesity Epidemic

    Science.gov (United States)

    Painter, James E.; Painter, Rosemary; Wang, Xinyue; Schuster, Margaret

    2017-01-01

    Obesity has been increasing in all age groups worldwide for the past several decades. Yet for hundreds of years before the last quarter of the 20th century, obesity was not an issue. The etiology and the cure for the obesity epidemic have been elusive. Weight reduction diets and behavior therapy have not produced the desired results. Perhaps…

  17. Obese fathers lead to an altered metabolism and obesity in their children in adulthood: review of experimental and human studies.

    Science.gov (United States)

    Ornellas, Fernanda; Carapeto, Priscila V; Mandarim-de-Lacerda, Carlos A; Aguila, Marcia B

    To discuss the recent literature on paternal obesity, focusing on the possible mechanisms of transmission of the phenotypes from the father to the children. A non-systematic review in the PubMed database found few publications in which paternal obesity was implicated in the adverse transmission of characteristics to offspring. Specific articles on epigenetics were also evaluated. As the subject is recent and still controversial, all articles were considered regardless of year of publication. Studies in humans and animals have established that paternal obesity impairs their hormones, metabolism, and sperm function, which can be transmitted to their offspring. In humans, paternal obesity results in insulin resistance/type 2 diabetes and increased levels of cortisol in umbilical cord blood, which increases the risk factors for cardiovascular disease. Notably, there is an association between body fat in parents and the prevalence of obesity in their daughters. In animals, paternal obesity led to offspring alterations on glucose-insulin homeostasis, hepatic lipogenesis, hypothalamus/feeding behavior, kidney of the offspring; it also impairs the reproductive potential of male offspring with sperm oxidative stress and mitochondrial dysfunction. An explanation for these observations (human and animal) is epigenetics, considered the primary tool for the transmission of phenotypes from the father to offspring, such as DNA methylation, histone modifications, and non-coding RNA. Paternal obesity can induce programmed phenotypes in offspring through epigenetics. Therefore, it can be considered a public health problem, affecting the children's future life. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  18. Expression studies of six human obesity-related genes in seven tissues from divergent pig breeds

    DEFF Research Database (Denmark)

    Cirera, S.; Jensen, M. S.; Elbrønd, V. S.

    2014-01-01

    Obesity has reached epidemic proportions globally and has become the cause of several major health risks worldwide. Presently, more than 100 loci have been related to obesity and metabolic traits in humans by genome-wide association studies. The complex genetic architecture behind obesity has...... triggered a need for the development of better animal models than rodents. The pig has emerged as a very promising biomedical model to study human obesity traits. In this study, we have characterized the expression patterns of six obesity-related genes, leptin (LEP), leptin receptor (LEPR), melanocortin 4...... minipigs) that deviate phenotypically and genetically from each other with respect to obesity traits. We observe significant differential expression for LEP, LEPR and ADIPOQ in muscle and in all three adipose tissues. Interestingly, in pancreas, LEP expression is only detected in the fat minipigs. FTO...

  19. Measurement of cortisol and testosterone in hair of obese and non-obese human subjects.

    Science.gov (United States)

    Chan, J; Sauvé, B; Tokmakejian, S; Koren, G; Van Uum, S

    2014-06-01

    Hair analysis has been demonstrated to accurately reflect exposure to drug abuse, environmental toxins and exogenous hormones. We tested the feasibility of measuring cortisol and testosterone in hair of healthy and obese subjects. A modified immunoassay (ELISA) originally developed for saliva was used. Hair, urine and blood samples were collected from young non-obese and obese patients. Perceived stress (PSS) was measured using a validated questionnaire. There was no difference in PSS between non-obese and obese subjects. Hair cortisol levels were significantly correlated with weight (r = 0.27, p cortisol levels did not correlate with age or urinary cortisol. There was a negative correlation between hair testosterone and age (r = -0.47, p cortisol over hair testosterone (C/T) was higher in the obese group than in the young non-obese group. The C/T ratio correlated positively with age (r = 0.56, p cortisol levels increase, while hair testosterone levels decrease with obesity. The hair C/T ratio was significantly correlated with age, BMI and waist circumference better than hair cortisol or testosterone alone. As hair collection is non-invasive and is not influenced by moment-to-moment variations, the measurement of hormones in hair is a useful tool in research and possibly clinical practice. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Relationship between Human Gut Microbiota and Interleukin 6 Levels in Overweight and Obese Adults

    Science.gov (United States)

    Background: Gut microbial diversity and abundance can profoundly impact human health. Research has shown that obese individuals are likely to have altered microbiota compared to lean individuals. Obesity is often considered a pro-inflammatory state, however the relationship between microbiota and i...

  1. A global evolutionary and metabolic analysis of human obesity gene risk variants.

    Science.gov (United States)

    Castillo, Joseph J; Hazlett, Zachary S; Orlando, Robert A; Garver, William S

    2017-09-05

    It is generally accepted that the selection of gene variants during human evolution optimized energy metabolism that now interacts with our obesogenic environment to increase the prevalence of obesity. The purpose of this study was to perform a global evolutionary and metabolic analysis of human obesity gene risk variants (110 human obesity genes with 127 nearest gene risk variants) identified using genome-wide association studies (GWAS) to enhance our knowledge of early and late genotypes. As a result of determining the mean frequency of these obesity gene risk variants in 13 available populations from around the world our results provide evidence for the early selection of ancestral risk variants (defined as selection before migration from Africa) and late selection of derived risk variants (defined as selection after migration from Africa). Our results also provide novel information for association of these obesity genes or encoded proteins with diverse metabolic pathways and other human diseases. The overall results indicate a significant differential evolutionary pattern for the selection of obesity gene ancestral and derived risk variants proposed to optimize energy metabolism in varying global environments and complex association with metabolic pathways and other human diseases. These results are consistent with obesity genes that encode proteins possessing a fundamental role in maintaining energy metabolism and survival during the course of human evolution. Copyright © 2017. Published by Elsevier B.V.

  2. The art of targeting gut microbiota for tackling human obesity

    NARCIS (Netherlands)

    Aguirre, M.; Venema, K.

    2015-01-01

    Recently, a great deal of interest has been expressed regarding strategies to tackle worldwide obesity because of its accelerated wide spread accompanied with numerous negative effects on health and high costs. Obesity has been traditionally associated with an imbalance in energy consumed when

  3. Genetics of obesity | Shawky | Egyptian Journal of Medical Human ...

    African Journals Online (AJOL)

    There is now widespread recognition that the continuing increase in the prevalence of obesity seen in many countries is likely to have major adverse effects on public health. The National Center for Health Statistics reports that 61% of adults in the United States are overweight and 26% are obese. Also The National Health ...

  4. Comparative analyses of QTLs influencing obesity and metabolic phenotypes in pigs and humans

    DEFF Research Database (Denmark)

    Pant, Sameer Dinkar; Karlskov-Mortensen, Peter; Jacobsen, Mette Juul

    2015-01-01

    The pig is a well-known animal model used to investigate genetic and mechanistic aspects of human disease biology. They are particularly useful in the context of obesity and metabolic diseases because other widely used models (e.g. mice) do not completely recapitulate key pathophysiological...... features associated with these diseases in humans. Therefore, we established a F2 pig resource population (n = 564) designed to elucidate the genetics underlying obesity and metabolic phenotypes. Segregation of obesity traits was ensured by using breeds highly divergent with respect to obesity traits...... in the parental generation. Several obesity and metabolic phenotypes were recorded (n = 35) from birth to slaughter (242 ± 48 days), including body composition determined at about two months of age (63 ± 10 days) via dual-energy x-ray absorptiometry (DXA) scanning. All pigs were genotyped using Illumina Porcine...

  5. Oxidative Stress in Obesity: A Critical Component in Human Diseases

    Directory of Open Access Journals (Sweden)

    Lucia Marseglia

    2014-12-01

    Full Text Available Obesity, a social problem worldwide, is characterized by an increase in body weight that results in excessive fat accumulation. Obesity is a major cause of morbidity and mortality and leads to several diseases, including metabolic syndrome, diabetes mellitus, cardiovascular, fatty liver diseases, and cancer. Growing evidence allows us to understand the critical role of adipose tissue in controlling the physic-pathological mechanisms of obesity and related comorbidities. Recently, adipose tissue, especially in the visceral compartment, has been considered not only as a simple energy depository tissue, but also as an active endocrine organ releasing a variety of biologically active molecules known as adipocytokines or adipokines. Based on the complex interplay between adipokines, obesity is also characterized by chronic low grade inflammation with permanently increased oxidative stress (OS. Over-expression of oxidative stress damages cellular structures together with under-production of anti-oxidant mechanisms, leading to the development of obesity-related complications. The aim of this review is to summarize what is known in the relationship between OS in obesity and obesity-related diseases.

  6. Determinants of testosterone levels in human male obesity.

    Science.gov (United States)

    Bekaert, Marlies; Van Nieuwenhove, Yves; Calders, Patrick; Cuvelier, Claude A; Batens, Arsène-Hélène; Kaufman, Jean-Marc; Ouwens, D Margriet; Ruige, Johannes B

    2015-09-01

    Testosterone (T) levels are decreased in obese men, but the underlying causes are incompletely understood. Our objective was to explore the relation between low (free) T levels and male obesity, by evaluating metabolic parameters, subcutaneous adipose tissue (SAT) aromatase expression, and parameters of the hypothalamic-pituitary-gonadal axis. We recruited 57 morbidly obese men [33 had type 2 diabetes (DM2)] and 25 normal-weight men undergoing abdominal surgery. Fourteen obese men also attended a follow-up, 2 years after gastric bypass surgery (GBS). Circulating T levels were quantified by LC-MS/MS, whereas free T levels were measured using serum equilibrium dialysis and sex hormone-binding globulin, luteinizing hormone, and follicle-stimulating hormone by immunoassay. SAT biopsies were used to determine adipocyte cell size and aromatase expression by real-time PCR. Total and free T levels were decreased in obese males versus controls, with a further decrease in obese men with DM2 versus obese men without DM2. There were no differences in aromatase expression among the study groups, and sex steroids did not correlate with aromatase expression. Pearson analysis revealed an inverse association between (free) T and SAT cell size, triglycerides, and HOMA-IR. Multivariate analysis confirmed the inverse association between (free) T and SAT cell size (β = -0.321, P = 0.037 and β = -0.441, P = 0.011, respectively), independent of age, triglycerides, HOMA-IR, obesity, or diabetes. T levels were normalized 2 years after GBS. These data suggest that SAT cell size rather than SAT aromatase expression or parameters of the hypothalamic-pituitary-gonadal axis is related to low T in male obesity, which points to adipose cell size-related metabolic changes as a major trigger in decreased T levels.

  7. Comparative Analyses of QTLs Influencing Obesity and Metabolic Phenotypes in Pigs and Humans.

    Directory of Open Access Journals (Sweden)

    Sameer D Pant

    Full Text Available The pig is a well-known animal model used to investigate genetic and mechanistic aspects of human disease biology. They are particularly useful in the context of obesity and metabolic diseases because other widely used models (e.g. mice do not completely recapitulate key pathophysiological features associated with these diseases in humans. Therefore, we established a F2 pig resource population (n = 564 designed to elucidate the genetics underlying obesity and metabolic phenotypes. Segregation of obesity traits was ensured by using breeds highly divergent with respect to obesity traits in the parental generation. Several obesity and metabolic phenotypes were recorded (n = 35 from birth to slaughter (242 ± 48 days, including body composition determined at about two months of age (63 ± 10 days via dual-energy x-ray absorptiometry (DXA scanning. All pigs were genotyped using Illumina Porcine 60k SNP Beadchip and a combined linkage disequilibrium-linkage analysis was used to identify genome-wide significant associations for collected phenotypes. We identified 229 QTLs which associated with adiposity- and metabolic phenotypes at genome-wide significant levels. Subsequently comparative analyses were performed to identify the extent of overlap between previously identified QTLs in both humans and pigs. The combined analysis of a large number of obesity phenotypes has provided insight in the genetic architecture of the molecular mechanisms underlying these traits indicating that QTLs underlying similar phenotypes are clustered in the genome. Our analyses have further confirmed that genetic heterogeneity is an inherent characteristic of obesity traits most likely caused by segregation or fixation of different variants of the individual components belonging to cellular pathways in different populations. Several important genes previously associated to obesity in human studies, along with novel genes were identified. Altogether, this study provides novel

  8. Obesity

    DEFF Research Database (Denmark)

    Heitmann, B L; Westerterp, K R; Loos, R J F

    2012-01-01

    programming for obesity via epigenetic changes in response to a 'Western diet' results in production of lipid-poor milk and metabolically efficient pups, contributing to the perpetuation of obesity throughout generations. Evolutionary insight from comparative physiology and ecology indicates that over...... generations activity-induced energy expenditure has remained the same compared to wild mammals, that energy balance might be dependant on protein balance, while the function of taste changed from detection of poison or energy to social drinking and social behaviour. At present, the impact of assortative...

  9. Clinically relevant known and candidate genes for obesity and their overlap with human infertility and reproduction.

    Science.gov (United States)

    Butler, Merlin G; McGuire, Austen; Manzardo, Ann M

    2015-04-01

    Obesity is a growing public health concern now reaching epidemic status worldwide for children and adults due to multiple problems impacting on energy intake and expenditure with influences on human reproduction and infertility. A positive family history and genetic factors are known to play a role in obesity by influencing eating behavior, weight and level of physical activity and also contributing to human reproduction and infertility. Recent advances in genetic technology have led to discoveries of new susceptibility genes for obesity and causation of infertility. The goal of our study was to provide an update of clinically relevant candidate and known genes for obesity and infertility using high resolution chromosome ideograms with gene symbols and tabular form. We used computer-based internet websites including PubMed to search for combinations of key words such as obesity, body mass index, infertility, reproduction, azoospermia, endometriosis, diminished ovarian reserve, estrogen along with genetics, gene mutations or variants to identify evidence for development of a master list of recognized obesity genes in humans and those involved with infertility and reproduction. Gene symbols for known and candidate genes for obesity were plotted on high resolution chromosome ideograms at the 850 band level. Both infertility and obesity genes were listed separately in alphabetical order in tabular form and those highlighted when involved with both conditions. By searching the medical literature and computer generated websites for key words, we found documented evidence for 370 genes playing a role in obesity and 153 genes for human reproduction or infertility. The obesity genes primarily affected common pathways in lipid metabolism, deposition or transport, eating behavior and food selection, physical activity or energy expenditure. Twenty-one of the obesity genes were also associated with human infertility and reproduction. Gene symbols were plotted on high resolution

  10. Obesity

    DEFF Research Database (Denmark)

    Morgen, Camilla Schmidt; Sørensen, Thorkild I A

    2014-01-01

    A new report provides compelling evidence of the high prevalence of overweight and obesity throughout the world. The prevalence has increased since 1980, but at different rates across ages, times and locations. Studies exploring the causes of these differences could aid development of effective...

  11. Differential representation of liver proteins in obese human subjects suggests novel biomarkers and promising targets for drug development in obesity.

    Science.gov (United States)

    Caira, Simonetta; Iannelli, Antonio; Sciarrillo, Rosaria; Picariello, Gianluca; Renzone, Giovanni; Scaloni, Andrea; Addeo, Pietro

    2017-12-01

    The proteome of liver biopsies from human obese (O) subjects has been compared to those of nonobese (NO) subjects using two-dimensional gel electrophoresis (2-DE). Differentially represented proteins were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)-based peptide mass fingerprinting (PMF) and nanoflow-liquid chromatography coupled to electrospray-tandem mass spectrometry (nLC-ESI-MS/MS). Overall, 61 gene products common to all of the liver biopsies were identified within 65 spots, among which 25 ones were differently represented between O and NO subjects. In particular, over-representation of short-chain acyl-CoA dehydrogenase, Δ(3,5)-Δ(2,4)dienoyl-CoA isomerase, acetyl-CoA acetyltransferase, glyoxylate reductase/hydroxypyruvate reductase, fructose-biphosphate aldolase B, peroxiredoxin I, protein DJ-1, catalase, α- and β-hemoglobin subunits, 3-mercaptopyruvate S-transferase, calreticulin, aminoacylase 1, phenazine biosynthesis-like domain-containing protein and a form of fatty acid-binding protein, together with downrepresentation of glutamate dehydrogenase, glutathione S-transferase A1, S-adenosylmethionine synthase 1A and a form of apolipoprotein A-I, was associated with the obesity condition. Some of these metabolic enzymes and antioxidant proteins have already been identified as putative diagnostic markers of liver dysfunction in animal models of steatosis or obesity, suggesting additional investigations on their role in these syndromes. Their differential representation in human liver was suggestive of their consideration as obesity human biomarkers and for the development of novel antiobesity drugs.

  12. Comparative Aspects of Human, Canine, and Feline Obesity and Factors Predicting Progression to Diabetes

    Directory of Open Access Journals (Sweden)

    Margarethe Hoenig

    2014-08-01

    Full Text Available Obesity and diabetes mellitus are common diseases in humans, dogs and cats and their prevalence is increasing. Obesity has been clearly identified as a risk factor for type 2 diabetes in humans and cats but recent data are missing in dogs, although there is evidence that the unprecedented rise in canine obesity in the last decade has led to a rise in canine diabetes of similar magnitude. The insulin resistance of obesity has often been portrayed as major culprit in the loss of glucose control; however, insulin resistance alone is not a good indicator of progression to diabetes in people or pets. A loss of beta cell function is necessary to provide the link to impaired fasting and post-prandial plasma glucose. Increased endogenous glucose output by the liver is also a prerequisite for the increase in fasting blood glucose when non-diabetic obese humans and pets develop diabetes. This may be due to decreased hepatic insulin sensitivity, decreased insulin concentrations, or a combination of both. While inflammation is a major link between obesity and diabetes in humans, there is little evidence that a similar phenomenon exists in cats. In dogs, more studies are needed to examine this important issue.

  13. Obesity Determines the Immunophenotypic Profile and Functional Characteristics of Human Mesenchymal Stem Cells From Adipose Tissue.

    Science.gov (United States)

    Pachón-Peña, Gisela; Serena, Carolina; Ejarque, Miriam; Petriz, Jordi; Duran, Xevi; Oliva-Olivera, W; Simó, Rafael; Tinahones, Francisco J; Fernández-Veledo, Sonia; Vendrell, Joan

    2016-04-01

    Adipose tissue is a major source of mesenchymal stem cells (MSCs), which possess a variety of properties that make them ideal candidates for regenerative and immunomodulatory therapies. Here, we compared the immunophenotypic profile of human adipose-derived stem cells (hASCs) from lean and obese individuals, and explored its relationship with the apparent altered plasticity of hASCs. We also hypothesized that persistent hypoxia treatment of cultured hASCs may be necessary but not sufficient to drive significant changes in mature adipocytes. hASCs were obtained from subcutaneous adipose tissue of healthy, adult, female donors undergoing abdominal plastic surgery: lean (n=8; body mass index [BMI]: 23±1 kg/m2) and obese (n=8; BMI: 35±5 kg/m2). Cell surface marker expression, proliferation and migration capacity, and adipogenic differentiation potential of cultured hASCs at two different oxygen conditions were studied. Compared with lean-derived hASCs, obese-derived hASCs demonstrated increased proliferation and migration capacity but decreased lipid droplet accumulation, correlating with a higher expression of human leukocyte antigen (HLA)-II and cluster of differentiation (CD) 106 and lower expression of CD29. Of interest, adipogenic differentiation modified CD106, CD49b, HLA-ABC surface protein expression, which was dependent on the donor's BMI. Additionally, low oxygen tension increased proliferation and migration of lean but not obese hASCs, which correlated with an altered CD36 and CD49b immunophenotypic profile. In summary, the differences observed in proliferation, migration, and differentiation capacity in obese hASCs occurred in parallel with changes in cell surface markers, both under basal conditions and during differentiation. Therefore, obesity is an important determinant of stem cell function independent of oxygen tension. The obesity-related hypoxic environment may have latent effects on human adipose tissue-derived mesenchymal stem cells (hASCs) with

  14. Impaired glucose-induced thermogenesis and arterial norepinephrine response persist after weight reduction in obese humans

    DEFF Research Database (Denmark)

    Astrup, A; Andersen, T; Christensen, N J

    1990-01-01

    A reduced thermic response and an impaired activation of the sympathetic nervous system (SNS) has been reported after oral glucose in human obesity. It is, however, not known whether the reduced SNS activity returns to normal along with weight reduction. The thermic effect of glucose was lower...... in eight obese patients than in matched control subjects (1.7% vs 9.2%, p less than 0.002). The increase in arterial norepinephrine after glucose was also blunted in the obese patients. After a 30-kg weight loss their glucose and lipid profiles were markedly improved but the thermic effect of glucose...

  15. Important mitochondrial proteins in human omental adipose tissue show reduced expression in obesity

    Directory of Open Access Journals (Sweden)

    Peter W. Lindinger

    2015-09-01

    Full Text Available Obesity is associated with impaired mitochondrial function. This study compares mitochondrial protein expression in omental fat in obese and non-obese humans. Omental adipose tissue was obtained by surgical biopsy, adipocytes were purified and mitochondria isolated. Using anion-exchange chromatography, SDS-PAGE and mass-spectrometry, 128 proteins with potentially different abundances in patient groups were identified, 62 of the 128 proteins are mainly localized in the mitochondria. Further quantification of 12 of these 62 proteins by immune dot blot analysis revealed four proteins citrate synthase, HADHA, LETM1 and mitofilin being inversely associated with BMI, and mitofilin being inversely correlated with gender.

  16. Important mitochondrial proteins in human omental adipose tissue show reduced expression in obesity.

    Science.gov (United States)

    Lindinger, Peter W; Christe, Martine; Eberle, Alex N; Kern, Beatrice; Peterli, Ralph; Peters, Thomas; Jayawardene, Kamburapola J I; Fearnley, Ian M; Walker, John E

    2015-09-01

    Obesity is associated with impaired mitochondrial function. This study compares mitochondrial protein expression in omental fat in obese and non-obese humans. Omental adipose tissue was obtained by surgical biopsy, adipocytes were purified and mitochondria isolated. Using anion-exchange chromatography, SDS-PAGE and mass-spectrometry, 128 proteins with potentially different abundances in patient groups were identified, 62 of the 128 proteins are mainly localized in the mitochondria. Further quantification of 12 of these 62 proteins by immune dot blot analysis revealed four proteins citrate synthase, HADHA, LETM1 and mitofilin being inversely associated with BMI, and mitofilin being inversely correlated with gender.

  17. Obesity.

    OpenAIRE

    Callaway, C W

    1987-01-01

    Obesity is not a single disease, but a variety of conditions resulting from different mechanisms and associated with various types and degrees of risks. To determine who should lose weight, how much weight should be lost, and how to undertake weight loss, the following types of information are needed: personal-demographic data, developmental patterns, family history, energy balance, body composition/fat distribution, psychological/behavioral measures, endocrine/metabolic measures, complicatio...

  18. Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans

    DEFF Research Database (Denmark)

    Reijnders, Dorien; Goossens, Gijs H; Hermes, Gerben D A

    2016-01-01

    The gut microbiota has been implicated in obesity and cardiometabolic diseases, although evidence in humans is scarce. We investigated how gut microbiota manipulation by antibiotics (7-day administration of amoxicillin, vancomycin, or placebo) affects host metabolism in 57 obese, prediabetic men....... Vancomycin, but not amoxicillin, decreased bacterial diversity and reduced Firmicutes involved in short-chain fatty acid and bile acid metabolism, concomitant with altered plasma and/or fecal metabolite concentrations. Adipose tissue gene expression of oxidative pathways was upregulated by antibiotics...

  19. The blind leading the obese: the molecular pathophysiology of a human obesity syndrome.

    Science.gov (United States)

    Sheffield, Val C

    2010-01-01

    Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder affecting multiple organ systems and resulting in blindness, obesity, cognitive impairment, and congenital defects. Interest in the etiology of this disorder stems, in part, from the fact that patients with BBS develop common clinical problems, including obesity, diabetes and hypertension. Twelve genes independently causing BBS have been identified. The heterogeneity is explained by the existence of two BBS complexes, the BBSome consisting of seven known BBS proteins, and the BBS chaperone complex consisting of three known BBS proteins. The formation of the BBSome requires the function of the BBS chaperone complex. Both mouse and zebrafish data support a role for BBS genes in cilia function, and in intracellular and intraflagellar trafficking. From the work described here, a common primary function of BBS proteins has emerged, specifically the mediation and regulation of microtubule-based intracellular transport.

  20. Skeletal muscle munc18c and syntaxin 4 in human obesity

    Directory of Open Access Journals (Sweden)

    Bessesen Daniel H

    2008-07-01

    Full Text Available Abstract Background Animal and cell culture data suggest a critical role for Munc18c and Syntaxin 4 proteins in insulin mediated glucose transport in skeletal muscle, but no studies have been published in humans. Methods We investigated the effect of a 12 vs. 48 hr fast on insulin action and skeletal muscle Munc18c and Syntaxin 4 protein in lean and obese subjects. Healthy lean (n = 14; age = 28.0 +/- 1.4 yr; BMI = 22.8 +/- 0.42 kg/m2 and obese subjects (n = 11; age = 34.6 +/- 2.3 yr; BMI = 36.1 +/- 1.5 kg/m2 were studied twice following a 12 and 48 hr fast. Skeletal muscle biopsies were obtained before a 3 hr 40 mU/m2/min hyperinsulinemic-euglycemic clamp with [6,6-2H2]glucose infusion. Results Glucose rate of disappearance (Rd during the clamp was lower in obese vs. lean subjects after the 12 hr fast (obese: 6.25 +/- 0.67 vs. lean: 9.42 +/- 1.1 mg/kgFFM/min, p = 0.007, and decreased significantly in both groups after the 48 hr fast (obese 3.49 +/- 0.31 vs. lean: 3.91 +/- 0.42 mg/kgFFM/min, p = 0.002. Munc18c content was not significantly different between lean and obese subjects after the 12 hour fast, and decreased after the 48 hr fast in both groups (p = 0.013. Syntaxin 4 content was not altered by obesity or fasting duration. There was a strong positive relationship between plasma glucose concentration and Munc18c content in lean and obese subjects during both 12 and 48 hr fasts (R2 = 0.447, p = 0.0015. Significant negative relationships were also found between Munc18c and FFA (p = 0.041, beta-hydroxybutyrate (p = 0.039, and skeletal muscle AKT content (p = 0.035 in lean and obese subjects. Conclusion These data indicate Munc18c and Syntaxin 4 are present in human skeletal muscle. Munc18c content was not significantly different between lean and obese subjects, and is therefore unlikely to explain obesity-induced insulin resistance. Munc18c content decreased after prolonged fasting in lean and obese subjects concurrently with reduced insulin

  1. Impact Response Comparison Between Parametric Human Models and Postmortem Human Subjects with a Wide Range of Obesity Levels.

    Science.gov (United States)

    Zhang, Kai; Cao, Libo; Wang, Yulong; Hwang, Eunjoo; Reed, Matthew P; Forman, Jason; Hu, Jingwen

    2017-10-01

    Field data analyses have shown that obesity significantly increases the occupant injury risks in motor vehicle crashes, but the injury assessment tools for people with obesity are largely lacking. The objectives of this study were to use a mesh morphing method to rapidly generate parametric finite element models with a wide range of obesity levels and to evaluate their biofidelity against impact tests using postmortem human subjects (PMHS). Frontal crash tests using three PMHS seated in a vehicle rear seat compartment with body mass index (BMI) from 24 to 40 kg/m 2 were selected. To develop the human models matching the PMHS geometry, statistical models of external body shape, rib cage, pelvis, and femur were applied to predict the target geometry using age, sex, stature, and BMI. A mesh morphing method based on radial basis functions was used to rapidly morph a baseline human model into the target geometry. The model-predicted body excursions and injury measures were compared to the PMHS tests. Comparisons of occupant kinematics and injury measures between the tests and simulations showed reasonable correlations across the wide range of BMI levels. The parametric human models have the capability to account for the obesity effects on the occupant impact responses and injury risks. © 2017 The Obesity Society.

  2. Thyroid Dysfunction Associated With Follicular Cell Steatosis in Obese Male Mice and Humans

    Science.gov (United States)

    Lee, Min Hee; Lee, Jung Uee; Joung, Kyong Hye; Kim, Yong Kyung; Ryu, Min Jeong; Lee, Seong Eun; Kim, Soung Jung; Chung, Hyo Kyun; Choi, Min Jeong; Chang, Joon Young; Lee, Sang-Hee; Kweon, Gi Ryang; Kim, Hyun Jin; Kim, Koon Soon; Kim, Seong-Min; Jo, Young Suk; Park, Jeongwon; Cheng, Sheue-Yann

    2015-01-01

    Adult thyroid dysfunction is a common endocrine disorder associated with an increased risk of cardiovascular disease and mortality. A recent epidemiologic study revealed a link between obesity and increased prevalence of hypothyroidism. It is conceivable that excessive adiposity in obesity might lead to expansion of the interfollicular adipose (IFA) depot or steatosis in thyroid follicular cells (thyroid steatosis, TS). In this study, we investigated the morphological and functional changes in thyroid glands of obese humans and animal models, diet-induced obese (DIO), ob/ob, and db/db mice. Expanded IFA depot and TS were observed in obese patients. Furthermore, DIO mice showed increased expression of lipogenesis-regulation genes, such as sterol regulatory element binding protein 1 (SREBP-1), peroxisome proliferator-activated receptor γ (PPARγ), acetyl coenzyme A carboxylase (ACC), and fatty acid synthetase (FASN) in the thyroid gland. Steatosis and ultrastructural changes, including distension of the endoplasmic reticulum (ER) and mitochondrial distortion in thyroid follicular cells, were uniformly observed in DIO mice and genetically obese mouse models, ob/ob and db/db mice. Obese mice displayed a variable degree of primary thyroid hypofunction, which was not corrected by PPARγ agonist administration. We propose that systemically increased adiposity is associated with characteristic IFA depots and TS and may cause or influence the development of primary thyroid failure. PMID:25555091

  3. The human gut microbiota: metabolism and perspective in obesity.

    Science.gov (United States)

    Gomes, Aline Corado; Hoffmann, Christian; Mota, João Felipe

    2018-04-18

    The gut microbiota has been recognized as an important factor in the development of metabolic diseases such as obesity and is considered an endocrine organ involved in the maintenance of energy homeostasis and host immunity. Dysbiosis can change the functioning of the intestinal barrier and the gut-associated lymphoid tissues (GALT) by allowing the passage of structural components of bacteria, such as lipopolysaccharides (LPS), which activate inflammatory pathways that may contribute to the development of insulin resistance. Furthermore, intestinal dysbiosis can alter the production of gastrointestinal peptides related to satiety, resulting in an increased food intake. In obese people, this dysbiosis seems be related to increases of the phylum Firmicutes, the genus Clostridium, and the species Eubacterium rectale, Clostridium coccoides, Lactobacillus reuteri, Akkermansia muciniphila, Clostridium histolyticum, and Staphylococcus aureus.

  4. Human Adipocytes Induce Inflammation and Atrophy in Muscle Cells During Obesity.

    Science.gov (United States)

    Pellegrinelli, Vanessa; Rouault, Christine; Rodriguez-Cuenca, Sergio; Albert, Victorine; Edom-Vovard, Frédérique; Vidal-Puig, Antonio; Clément, Karine; Butler-Browne, Gillian S; Lacasa, Danièle

    2015-09-01

    Inflammation and lipid accumulation are hallmarks of muscular pathologies resulting from metabolic diseases such as obesity and type 2 diabetes. During obesity, the hypertrophy of visceral adipose tissue (VAT) contributes to muscle dysfunction, particularly through the dysregulated production of adipokines. We have investigated the cross talk between human adipocytes and skeletal muscle cells to identify mechanisms linking adiposity and muscular dysfunctions. First, we demonstrated that the secretome of obese adipocytes decreased the expression of contractile proteins in myotubes, consequently inducing atrophy. Using a three-dimensional coculture of human myotubes and VAT adipocytes, we showed the decreased expression of genes corresponding to skeletal muscle contractility complex and myogenesis. We demonstrated an increased secretion by cocultured cells of cytokines and chemokines with interleukin (IL)-6 and IL-1β as key contributors. Moreover, we gathered evidence showing that obese subcutaneous adipocytes were less potent than VAT adipocytes in inducing these myotube dysfunctions. Interestingly, the atrophy induced by visceral adipocytes was corrected by IGF-II/insulin growth factor binding protein-5. Finally, we observed that the skeletal muscle of obese mice displayed decreased expression of muscular markers in correlation with VAT hypertrophy and abnormal distribution of the muscle fiber size. In summary, we show the negative impact of obese adipocytes on muscle phenotype, which could contribute to muscle wasting associated with metabolic disorders. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  5. Effects of obesity on occupant responses in frontal crashes: a simulation analysis using human body models.

    Science.gov (United States)

    Shi, Xiangnan; Cao, Libo; Reed, Matthew P; Rupp, Jonathan D; Hu, Jingwen

    2015-01-01

    The objective of this study is to investigate the effects of obesity on occupant responses in frontal crashes using whole-body human finite element (FE) models representing occupants with different obesity levels. In this study, the geometry of THUMS 4 midsize male model was varied using mesh morphing techniques with target geometries defined by statistical models of external body contour and exterior ribcage geometry. Models with different body mass indices (BMIs) were calibrated against cadaver test data under high-speed abdomen loading and frontal crash conditions. A parametric analysis was performed to investigate the effects of BMI on occupant injuries in frontal crashes based on the Taguchi method while controlling for several vehicle design parameters. Simulations of obese occupants predicted significantly higher risks of injuries to the thorax and lower extremities in frontal crashes compared with non-obese occupants, which is consistent with previous field data analyses. These higher injury risks are mainly due to the increased body mass and relatively poor belt fit caused by soft tissues for obese occupants. This study demonstrated the feasibility of using a parametric human FE model to investigate the obesity effects on occupant responses in frontal crashes.

  6. Exercise, Obesity, and Cutaneous Wound Healing: Evidence from Rodent and Human Studies.

    Science.gov (United States)

    Pence, Brandt D; Woods, Jeffrey A

    2014-01-01

    Significance: Impaired cutaneous wound healing is a major health concern. Obesity has been shown in a number of studies to impair wound healing, and chronic nonhealing wounds in obesity and diabetes are a major cause of limb amputations in the United States. Recent Advances: Recent evidence indicates that aberrant wound site inflammation may be an underlying cause for delayed healing. Obesity, diabetes, and other conditions such as stress and aging can result in a chronic low-level inflammatory state, thereby potentially affecting wound healing negatively. Critical Issues: Interventions which can speed the healing rate in individuals with slowly healing or nonhealing wounds are of critical importance. Recently, physical exercise training has been shown to speed healing in both aged and obese mice and in older adults. Exercise is a relatively low-cost intervention strategy which may be able to be used clinically to prevent or treat impairments in the wound-healing process. Future Directions: Little is known about the mechanisms by which exercise speeds healing. Future translational studies should address potential mechanisms for these exercise effects. Additionally, clinical studies in obese humans are necessary to determine if findings in obese rodent models translate to the human population.

  7. Anti-ghrelin immunoglobulins modulate ghrelin stability and its orexigenic effect in obese mice and humans

    Science.gov (United States)

    Takagi, Kuniko; Legrand, Romain; Asakawa, Akihiro; Amitani, Haruka; François, Marie; Tennoune, Naouel; Coëffier, Moïse; Claeyssens, Sophie; do Rego, Jean-Claude; Déchelotte, Pierre; Inui, Akio; Fetissov, Sergueï O.

    2013-01-01

    Obese individuals often have increased appetite despite normal plasma levels of the main orexigenic hormone ghrelin. Here we show that ghrelin degradation in the plasma is inhibited by ghrelin-reactive IgG immunoglobulins, which display increased binding affinity to ghrelin in obese patients and mice. Co-administration of ghrelin together with IgG from obese individuals, but not with IgG from anorectic or control patients, increases food intake in rats. Similarly, chronic injections of ghrelin together with IgG from ob/ob mice increase food intake, meal frequency and total lean body mass of mice. These data reveal that in both obese humans and mice, IgG with increased affinity for ghrelin enhances ghrelin’s orexigenic effect, which may contribute to increased appetite and overeating. PMID:24158035

  8. Functional polymorphism of IL-1 alpha and its potential role in obesity in humans and mice.

    Directory of Open Access Journals (Sweden)

    Jae-Young Um

    Full Text Available Proinflammatory cytokines secreted from adipose tissue contribute to the morbidity associated with obesity. IL-1α is one of the proinflammatory cytokines; however, it has not been clarified whether IL-1α may also cause obesity. In this study, we investigated whether polymorphisms in IL-1α contribute to human obesity. A total of 260 obese subjects were genotyped for IL-1α C-889T (rs1800587 and IL-1α G+4845T (rs17561. Analyses of genotype distributions revealed that both IL-1α polymorphisms C-889T (rs1800587 and G+4845T (rs17561 were associated with an increase in body mass index in obese healthy women. In addition, the effect of rs1800587 on the transcriptional activity of IL-1α was explored in pre-adipocyte 3T3-L1 cells. Significant difference was found between the rs1800587 polymorphism in the regulatory region of the IL-1α gene and transcriptional activity. We extended these observations in vivo to a high-fat diet-induced obese mouse model and in vitro to pre-adipocyte 3T3-L1 cells. IL-1α levels were dramatically augmented in obese mice, and triglyceride was increased 12 hours after IL-1α injection. Taken together, IL-1α treatment regulated the differentiation of preadipocytes. IL-1α C-889T (rs1800587 is a functional polymorphism of IL-1α associated with obesity. IL-1α may have a critical function in the development of obesity.

  9. Proteasome Dysfunction Associated to Oxidative Stress and Proteotoxicity in Adipocytes Compromises Insulin Sensitivity in Human Obesity

    Science.gov (United States)

    Díaz-Ruiz, Alberto; Guzmán-Ruiz, Rocío; Moreno, Natalia R.; García-Rios, Antonio; Delgado-Casado, Nieves; Membrives, Antonio; Túnez, Isaac; El Bekay, Rajaa; Fernández-Real, José M.; Tovar, Sulay; Diéguez, Carlos; Tinahones, Francisco J.; Vázquez-Martínez, Rafael; López-Miranda, José

    2015-01-01

    Abstract Aims: Obesity is characterized by a low-grade systemic inflammatory state and adipose tissue (AT) dysfunction, which predispose individuals to the development of insulin resistance (IR) and metabolic disease. However, a subset of obese individuals, referred to as metabolically healthy obese (MHO) individuals, are protected from obesity-associated metabolic abnormalities. Here, we aim at identifying molecular factors and pathways in adipocytes that are responsible for the progression from the insulin-sensitive to the insulin-resistant, metabolically unhealthy obese (MUHO) phenotype. Results: Proteomic analysis of paired samples of adipocytes from subcutaneous (SC) and omental (OM) human AT revealed that both types of cells are altered in the MUHO state. Specifically, the glutathione redox cycle and other antioxidant defense systems as well as the protein-folding machinery were dysregulated and endoplasmic reticulum stress was increased in adipocytes from IR subjects. Moreover, proteasome activity was also compromised in adipocytes of MUHO individuals, which was associated with enhanced accumulation of oxidized and ubiquitinated proteins in these cells. Proteasome activity was also impaired in adipocytes of diet-induced obese mice and in 3T3-L1 adipocytes exposed to palmitate. In line with these data, proteasome inhibition significantly impaired insulin signaling in 3T3-L1 adipocytes. Innovation: This study provides the first evidence of the occurrence of protein homeostasis deregulation in adipocytes in human obesity, which, together with oxidative damage, interferes with insulin signaling in these cells. Conclusion: Our results suggest that proteasomal dysfunction and impaired proteostasis in adipocytes, resulting from protein oxidation and/or misfolding, constitute major pathogenic mechanisms in the development of IR in obesity. Antioxid. Redox Signal. 23, 597–612. PMID:25714483

  10. Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity.

    Science.gov (United States)

    Fu, Zhiyao; Berhane, Feven; Fite, Alemu; Seyoum, Berhane; Abou-Samra, Abdul B; Zhang, Ren

    2014-05-23

    Lipasin (also known as C19ORF80, RIFL, ANGPTL8 and betatrophin) is a newly discovered circulating factor that regulates lipid metabolism and promotes pancreatic β-cell proliferation. Whether circulating levels of lipasin in humans are altered in a) type 2 diabetes; b) obesity and c) the postprandial state, however, is unknown. The current study aimed to compare serum lipasin levels in those who were a) non-diabetic (N=15) or diabetic (BMI- and age-matched; N=14); b) lean or obese (N=53 totally) and c) fasting and 2 hours following a defined meal (N=12). Serum lipasin levels were determined by the enzyme-linked immunosorbent assay. Lipasin levels [mean±SEM] were increased by more than two fold (Plipasin levels were positively correlated with BMI (rho=0.49, Plipasin/betatrophin is nutritionally-regulated hepatokine that is increased in human type 2 diabetes and obesity.

  11. Stigmatization of obese individuals by human resource professionals: an experimental study

    Directory of Open Access Journals (Sweden)

    Giel Katrin E

    2012-07-01

    Full Text Available Abstract Background Weight-related stigmatization is a public health problem. It impairs the psychological well-being of obese individuals and hinders them from adopting weight-loss behaviors. We conducted an experimental study to investigate weight stigmatization in work settings using a sample of experienced human resource (HR professionals from a real-life employment setting. Methods In a cross-sectional, computer-based experimental study, a volunteer sample of 127 HR professionals (age: 41.1 ± 10.9 yrs., 56% female, who regularly make career decisions about other people, evaluated individuals shown in standardized photographs regarding work-related prestige and achievements. The photographed individuals differed with respect to gender, ethnicity, and Body Mass Index (BMI. Results Participants underestimated the occupational prestige of obese individuals and overestimated it for normal-weight individuals. Obese people were more often disqualified from being hired and less often nominated for a supervisory position, while non-ethnic normal-weight individuals were favored. Stigmatization was most pronounced in obese females. Conclusions The data suggest that HR professionals are prone to pronounced weight stigmatization, especially in women. This highlights the need for interventions targeting this stigmatization as well as stigma-management strategies for obese individuals. Weight stigmatization and its consequences needs to be a topic that is more strongly addressed in clinical obesity care.

  12. Stigmatization of obese individuals by human resource professionals: an experimental study.

    Science.gov (United States)

    Giel, Katrin E; Zipfel, Stephan; Alizadeh, Manuela; Schäffeler, Norbert; Zahn, Carmen; Wessel, Daniel; Hesse, Friedrich W; Thiel, Syra; Thiel, Ansgar

    2012-07-16

    Weight-related stigmatization is a public health problem. It impairs the psychological well-being of obese individuals and hinders them from adopting weight-loss behaviors. We conducted an experimental study to investigate weight stigmatization in work settings using a sample of experienced human resource (HR) professionals from a real-life employment setting. In a cross-sectional, computer-based experimental study, a volunteer sample of 127 HR professionals (age: 41.1 ± 10.9 yrs., 56% female), who regularly make career decisions about other people, evaluated individuals shown in standardized photographs regarding work-related prestige and achievements. The photographed individuals differed with respect to gender, ethnicity, and Body Mass Index (BMI). Participants underestimated the occupational prestige of obese individuals and overestimated it for normal-weight individuals. Obese people were more often disqualified from being hired and less often nominated for a supervisory position, while non-ethnic normal-weight individuals were favored. Stigmatization was most pronounced in obese females. The data suggest that HR professionals are prone to pronounced weight stigmatization, especially in women. This highlights the need for interventions targeting this stigmatization as well as stigma-management strategies for obese individuals. Weight stigmatization and its consequences needs to be a topic that is more strongly addressed in clinical obesity care.

  13. Obesity and Low-Grade Inflammation Increase Plasma Follistatin-Like 3 in Humans

    DEFF Research Database (Denmark)

    Brandt, Claus; Pedersen, Maria; Rinnov, Anders

    2014-01-01

    , plasma leptin, fasting insulin, and HOMA B and negatively with HOMA S. Furthermore plasma fstl3 correlated positively with plasma TNF-α and IL-6 levels. Infusion of LPS and TNF-α, but not IL-6 and insulin, increased plasma fstl3 in humans. CONCLUSION: Plasma fstl3 is increased in obese subjects...

  14. Obesity and Low-Grade Inflammation Increase Plasma Follistatin-Like 3 in Humans

    Directory of Open Access Journals (Sweden)

    Claus Brandt

    2014-01-01

    Full Text Available Background. Rodent models suggest that follistatin-like 3 (fstl3 is associated with diabetes and obesity. In humans, plasma fstl3 is reduced with gestational diabetes. In vitro, TNF-α induces fstl3 secretion, which suggests a link to inflammation. Objective. To elucidate the association between plasma fstl3 and obesity, insulin resistance, and low-grade inflammation in humans. Study Design. Plasma fstl3 levels were determined in a cross-sectional study including three groups: patients with type 2 diabetes, impaired glucose tolerance, and healthy controls. In addition, lipopolysaccharide (LPS, TNF-α, or interleukin-6 (IL-6 as well as a hyperinsulinemic euglycemic clamp were used to examine if plasma fstl3 was acutely regulated in humans. Results. Plasma fstl3 was increased in obese subjects independent of glycemic state. Moreover, plasma fstl3 was positively correlated with fat mass, plasma leptin, fasting insulin, and HOMA B and negatively with HOMA S. Furthermore plasma fstl3 correlated positively with plasma TNF-α and IL-6 levels. Infusion of LPS and TNF-α, but not IL-6 and insulin, increased plasma fstl3 in humans. Conclusion. Plasma fstl3 is increased in obese subjects and associated with fat mass and low-grade inflammation. Furthermore, TNF-α increased plasma fstl3, suggesting that TNF-α is one of the inflammatory drivers of increased systemic levels of fstl3.

  15. Human muscle fiber type-specific insulin signaling: Impact of obesity and type 2 diabetes

    DEFF Research Database (Denmark)

    Albers, Peter Hjorth; Pedersen, Andreas J T; Birk, Jesper Bratz

    2015-01-01

    -responses to insulin adjusted for protein level were not different between fiber types. Independently of fiber type, insulin signaling was similar (TBC1D1, GS and PDH-E1α) or decreased (Akt and TBC1D4) in muscle from patients with type 2 diabetes compared to lean and obese subjects. We conclude that human type I...

  16. Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans

    DEFF Research Database (Denmark)

    Donkin, Ida; Versteyhe, Soetkin; Ingerslev, Lars R.

    2016-01-01

    of morbidly obese men, surgery-induced weight loss was associated with a dramatic remodeling of sperm DNA methylation, notably at genetic locations implicated in the central control of appetite. Our data provide evidence that the epigenome of human spermatozoa dynamically changes under environmental pressure...

  17. Human obesity associated with an intronic SNP in the brain-derived neurotrophic factor locus

    Science.gov (United States)

    Brain-derived neurotrophic factor (BDNF) plays a key role in energy balance. In population studies, SNPs of the BDNF locus have been linked to obesity, but the mechanism by which these variants cause weight gain is unknown. Here, we examined human hypothalamic BDNF expression in association with 44 ...

  18. Is there visceral adipose tissue (VAT) intracellular hypercortisolism in human obesity?

    Science.gov (United States)

    Alfonso, B; Araki, T; Zumoff, B

    2013-05-01

    The fact that obesity is a prominent feature of Cushing's syndrome (systemic hypercortisolism of adrenocortical origin) stimulated a 40-year search for evidence of systemic hypercortisolism in human obesity. That search has failed to find such evidence. For the past 15 years, however, studies have been done to evaluate a possible alternative type of hypercortisolism in obesity, namely visceral adipose tissue (VAT) intracellular hypercortisolism. The current review summarizes the evidence published so far about this possibility. There have been three types of evidence studied: direct measurement of the VAT levels of 11β-hydroxysteroid dehydrogenase type I (11-HSD-1), which converts biologically inactive cortisone to biologically active cortisol; direct measurement of splanchnic cortisol production; and evaluation of the effect of a specific inhibitor of 11-HSD-1 on metabolic abnormalities associated with obesity, particularly diabetes mellitus. The results are complex and difficult to interpret. Our conclusion is that the presence of VAT intracellular hypercortisolism in human obesity is possible but unlikely. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Lack of support for the association between GAD2 polymorphisms and severe human obesity.

    Directory of Open Access Journals (Sweden)

    Michael M Swarbrick

    2005-09-01

    Full Text Available The demonstration of association between common genetic variants and chronic human diseases such as obesity could have profound implications for the prediction, prevention, and treatment of these conditions. Unequivocal proof of such an association, however, requires independent replication of initial positive findings. Recently, three (-243 A>G, +61450 C>A, and +83897 T>A single nucleotide polymorphisms (SNPs within glutamate decarboxylase 2 (GAD2 were found to be associated with class III obesity (body mass index > 40 kg/m2. The association was observed among 188 families (612 individuals segregating the condition, and a case-control study of 575 cases and 646 lean controls. Functional data supporting a pathophysiological role for one of the SNPs (-243 A>G were also presented. The gene GAD2 encodes the 65-kDa subunit of glutamic acid decarboxylase-GAD65. In the present study, we attempted to replicate this association in larger groups of individuals, and to extend the functional studies of the -243 A>G SNP. Among 2,359 individuals comprising 693 German nuclear families with severe, early-onset obesity, we found no evidence for a relationship between the three GAD2 SNPs and obesity, whether SNPs were studied individually or as haplotypes. In two independent case-control studies (a total of 680 class III obesity cases and 1,186 lean controls, there was no significant relationship between the -243 A>G SNP and obesity (OR = 0.99, 95% CI 0.83-1.18, p = 0.89 in the pooled sample. These negative findings were recapitulated in a meta-analysis, incorporating all published data for the association between the -243G allele and class III obesity, which yielded an OR of 1.11 (95% CI 0.90-1.36, p = 0.28 in a total sample of 1,252 class III obese cases and 1,800 lean controls. Moreover, analysis of common haplotypes encompassing the GAD2 locus revealed no association with severe obesity in families with the condition. We also obtained functional data for the

  20. Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity

    OpenAIRE

    Zhiyao Fu; Feven Berhane; Alemu Fite; Berhane Seyoum; Abdul B. Abou-Samra; Ren Zhang

    2014-01-01

    Lipasin (also known as C19ORF80, RIFL, ANGPTL8 and betatrophin) is a newly discovered circulating factor that regulates lipid metabolism and promotes pancreatic ?-cell proliferation. Whether circulating levels of lipasin in humans are altered in a) type 2 diabetes; b) obesity and c) the postprandial state, however, is unknown. The current study aimed to compare serum lipasin levels in those who were a) non-diabetic (N = 15) or diabetic (BMI- and age-matched; N = 14); b) lean or obese (N = 53 ...

  1. Human brown adipose tissue as a target for obesity management; beyond cold-induced thermogenesis.

    Science.gov (United States)

    Loh, R K C; Kingwell, B A; Carey, A L

    2017-11-01

    Elevating energy expenditure via adaptive thermogenesis in brown adipose tissue (BAT) is a potential strategy to reverse obesity. Much early enthusiasm for this approach, based on rodent studies, was tempered by the belief that BAT was relatively inconsequential in healthy adult humans. Interest was reinvigorated a decade ago when a series of studies re-identified BAT, primarily in upper thoracic regions, in adults. Despite the ensuing explosion of pre-clinical investigations and identification of an extensive list of potential target molecules for BAT recruitment, our understanding of human BAT physiology remains limited, particularly regarding interventions which might hold therapeutic promise. Cold-induced BAT thermogenesis (CIT) has been well studied, although is not readily translatable as an anti-obesity approach, whereas little is known regarding the role of BAT in human diet-induced thermogenesis (DIT). Furthermore, human studies dedicated to translating known pharmacological mechanisms of adipose browning from animal models are sparse. Several lines of recent evidence suggest that molecular regulation and physiology of human BAT differ to that of laboratory rodents, which form the majority of our knowledge base. This review will summarize knowledge on CIT and expand upon the current understanding and evidence gaps related to human adaptive thermogenesis via mechanisms other than cold. © 2017 World Obesity Federation.

  2. Obesity interferes with the orosensory detection of long-chain fatty acids in humans.

    Science.gov (United States)

    Chevrot, Michael; Passilly-Degrace, Patricia; Ancel, Déborah; Bernard, Arnaud; Enderli, Géraldine; Gomes, Marlène; Robin, Isabelle; Issanchou, Sylvie; Vergès, Bruno; Nicklaus, Sophie; Besnard, Philippe

    2014-05-01

    The association between the orosensory detection of lipids, preference for fatty foods, and body mass index (BMI; in kg/m(2)) is controversial in humans. We explored the oral lipid-sensing system and the orosensory-induced autonomic reflex system in lean and obese subjects. Lean (BMI: 19 to obese (BMI >30; n = 29) age-matched men were enrolled. Their oral threshold sensitivity to linoleic acid (LA) was determined by using a 3-alternative forced-choice ascending procedure, and their eating habits were established by the analysis of 4 consecutive 24-h food-consumption diaries. The effect of brief oral lipid stimulations on plasma triglyceride [(TG)pl] concentrations was analyzed in overnight-fasted lean and obese individuals subjected to a whole-mouth stimulation (sip-and-spit procedure) with a control or 1% LA emulsions for 5 min according to a within-subject randomized design. A large distribution of LA detection was shown in both groups. Mean detection thresholds were 0.053% (wt:wt) and 0.071% (wt:wt) in lean and obese subjects, respectively. No relation between the LA detection threshold and BMI was observed. The 5 subjects who detected only the higher concentration of LA (5% wt:wt) or were unable to distinguish properly between control and LA emulsions were obese. An analysis of dietary habits showed that these obese LA nontasters consumed more lipids and energy than did all other subjects. Brief whole-mouth stimulations (sip-and-spit procedure) with a control or 1% LA emulsion revealed an LA-mediated rise in (TG)pl concentrations in overnight-fasted, lean subjects. The origin of this change seemed to be hepatic. This (TG)pl upregulation was not shown in obese subjects, which suggested that obesity led to disturbances in the oral-brainstem-periphery loop. Altogether, these data strongly suggest that obesity may interfere with the orosensory system responsible for the detection of free long-chain fatty acids in humans. This trial was registered at clinicaltrials

  3. DNAJB3/HSP-40 cochaperone is downregulated in obese humans and is restored by physical exercise.

    Directory of Open Access Journals (Sweden)

    Jehad Abubaker

    Full Text Available Obesity is a major risk factor for a myriad of disorders such as insulin resistance and diabetes. The mechanisms underlying these chronic conditions are complex but low grade inflammation and alteration of the endogenous stress defense system are well established. Previous studies indicated that impairment of HSP-25 and HSP-72 was linked to obesity, insulin resistance and diabetes in humans and animals while their induction was associated with improved clinical outcomes. In an attempt to identify additional components of the heat shock response that may be dysregulated by obesity, we used the RT(2-Profiler PCR heat shock array, complemented with RT-PCR and validated by Western blot and immunohistochemistry. Using adipose tissue biopsies and PBMC of non-diabetic lean and obese subjects, we report the downregulation of DNAJB3 cochaperone mRNA and protein in obese that negatively correlated with percent body fat (P = 0.0001, triglycerides (P = 0.035 and the inflammatory chemokines IP-10 and RANTES (P = 0.036 and P = 0.02, respectively. DNAJB positively correlated with maximum oxygen consumption (P = 0.031. Based on the beneficial effect of physical exercise, we investigated its possible impact on DNAJB3 expression and indeed, we found that exercise restored the expression of DNAJB3 in obese subjects with a concomitant decrease of phosphorylated JNK. Using cell lines, DNAJB3 protein was reduced following treatment with palmitate and tunicamycin which is suggestive of the link between the expression of DNAJB3 and the activation of the endoplasmic reticulum stress. DNAJB3 was also shown to coimmunoprecipiate with JNK and IKKβ stress kinases along with HSP-72 and thus, suggesting its potential role in modulating their activities. Taken together, these data suggest that DNAJB3 can potentially play a protective role against obesity.

  4. Adipose Tissue 12/15 Lipoxygenase Pathway in Human Obesity and Diabetes

    Science.gov (United States)

    Lieb, David C.; Brotman, Joshua J.; Hatcher, Margaret A.; Aye, Myo S.; Cole, Banumathi K.; Haynes, Bronson A.; Wohlgemuth, Stephen D.; Fontana, Mark A.; Beydoun, Hind; Nadler, Jerry L.

    2014-01-01

    Context: Visceral adipose tissue (VAT) is a key contributor to chronic inflammation in obesity. The 12/15-lipoxygenase pathway (ALOX) is present in adipose tissue (AT) and leads to inflammatory cascades that are causal for the onset of insulin resistance in rodent models of obesity. Objective: The pathophysiology of the ALOX 12/15 pathway in human AT is unknown. We characterized the ALOX pathway in different AT depots in obese humans with or without type 2 diabetes (T2D). Design: This study includes a cross-sectional cohort of 46 morbidly obese (body mass index >39 kg/m2) nondiabetic (n = 25) and T2D (n = 21) subjects. Setting: This study was conducted at Eastern Virginia Medical School (Norfolk, Virginia) in collaboration with Sentara Metabolic and Weight Loss Surgery Center (Sentara Medical Group, Norfolk, Virginia). Patients: Twenty-five obese (body mass index 44.8 ± 4.4 kg/m2) nondiabetic (hemoglobin A1c 5.83% ± 0.27%) and 21 obese (43.4 ± 4.1 kg/m2) and T2D (hemoglobin A1c 7.66% ± 1.22%) subjects were included in the study. The subjects were age matched and both groups had a bias toward female gender. Main Outcomes and Measures: Expression of ALOX isoforms along with fatty acid substrates and downstream lipid metabolites were measured. Correlations with depot-specific inflammatory markers were also established. Results: ALOX 12 expression and its metabolite 12(S)-hydroxyeicosatetraenoic acid were significantly increased in the VAT of T2D subjects. ALOX 15A was exclusively expressed in VAT in both groups. ALOX 12 expression positively correlated with expression of inflammatory genes IL-6, IL-12a, CXCL10, and lipocalin-2. Conclusions: ALOX 12 may have a critical role in regulation of inflammation in VAT in obesity and T2D. Selective ALOX 12 inhibitors may constitute a new approach to limit AT inflammation in human obesity. PMID:24955608

  5. Abnormal epigenetic changes during differentiation of human skeletal muscle stem cells from obese subjects

    DEFF Research Database (Denmark)

    Davegårdh, Cajsa; Broholm, Christa; Perfilyev, Alexander

    2017-01-01

    subjects. Interestingly, numerous genes implicated in metabolic diseases and epigenetic regulation showed differential methylation and expression during differentiation only in obese subjects. CONCLUSIONS: Our study identifies IL-32 as a novel myogenic regulator, provides a comprehensive map of the dynamic......BACKGROUND: Human skeletal muscle stem cells are important for muscle regeneration. However, the combined genome-wide DNA methylation and expression changes taking place during adult myogenesis have not been described in detail and novel myogenic factors may be discovered. Additionally, obesity...... is associated with low relative muscle mass and diminished metabolism. Epigenetic alterations taking place during myogenesis might contribute to these defects. METHODS: We used Infinium HumanMethylation450 BeadChip Kit (Illumina) and HumanHT-12 Expression BeadChip (Illumina) to analyze genome-wide DNA...

  6. Advances on human milk hormones and protection against obesity.

    Science.gov (United States)

    Savino, F; Benetti, S; Liguori, S A; Sorrenti, M; Cordero Di Montezemolo, L

    2013-11-03

    Extensive research shows that breast milk could have positive health effects not limited to infancy, but extend into childhood and adulthood. Recently many studies have provided new evidence on the long—term positive effects of breastfeeding, in particular protection against obesity and type 2 diabetes, suggesting that breast milk may have a role in the programming of later metabolic diseases. The mechanism throughout breastfeeding that exerts these effects has been a major focus of interest for researchers and it is still not completely known. There are some hints for biological plausibility of beneficial effects of breastfeeding including macronutrient intake, hormonal and behavioural mechanisms related to breast milk composition. Breast milk biochemical components, such as protein quantity and quality, polyunsaturated fatty acids, oligosaccharides, cytokines and hormones, in particular leptin, adiponectin and resistin together with the breastfeeding practice itself can influence infants feeding behaviour and regulation of growth and appetite control later in life. Further research is needed to confirm the possibility that hormones present in breast milk exert a metabolic and beneficial effects.

  7. Effects of aging on basal fat oxidation in obese humans

    DEFF Research Database (Denmark)

    Solomon, Thomas; Marchetti, Christine M; Krishnan, Raj K

    2008-01-01

    = .16); however, waist circumference was not different between groups (104.3 +/- 10.3 vs 102.1 +/- 12.6 cm, P = .65). Basal fat oxidation was 22% lower (1.42 +/- 0.14 vs 1.17 +/- 0.22 mg/kg fat-free mass per minute, P = .03) in older subjects. The VO(2)max was also decreased in older individuals (44.......6 +/- 7.1 vs 38.3 +/- 6.0 mL/kg fat-free mass per minute, P = .03); but insulin sensitivity, lipemia, and leptinemia were not different between groups (P > .05). Fat oxidation was most related to age (r = -0.61, P = .003) and VO(2)max (r = 0.52, P = .01). These data suggest that aging per se......Basal fat oxidation decreases with age. In obesity, it is not known whether this age-related process occurs independently of changes in body composition and insulin sensitivity. Therefore, body composition, resting energy expenditure, basal substrate oxidation, and maximal oxygen consumption (VO(2...

  8. Enteropeptidase: a gene associated with a starvation human phenotype and a novel target for obesity treatment.

    Directory of Open Access Journals (Sweden)

    Sandrine Braud

    Full Text Available BACKGROUND: Obesity research focuses essentially on gene targets associated with the obese phenotype. None of these targets have yet provided a viable drug therapy. Focusing instead on genes that are involved in energy absorption and that are associated with a "human starvation phenotype", we have identified enteropeptidase (EP, a gene associated with congenital enteropeptidase deficiency, as a novel target for obesity treatment. The advantages of this target are that the gene is expressed exclusively in the brush border of the intestine; it is peripheral and not redundant. METHODOLOGY/PRINCIPAL FINDINGS: Potent and selective EP inhibitors were designed around a boroarginine or borolysine motif. Oral administration of these compounds to mice restricted the bioavailability of dietary energy, and in a long-term treatment it significantly diminished the rate of increase in body weight, despite ad libitum food intake. No adverse reactions of the type seen with lipase inhibitors, such as diarrhea or steatorrhea, were observed. This validates EP as a novel, druggable target for obesity treatment. CONCLUSIONS: In vivo testing of novel boroarginine or borolysine-based EP inhibitors validates a novel approach to the treatment of obesity.

  9. Metabolic regulation and the anti-obesity perspectives of human brown fat.

    Science.gov (United States)

    Scheele, Camilla; Nielsen, Søren

    2017-08-01

    Activation of brown adipose tissue (BAT) in adult humans increase glucose and fatty acid clearance as well as resting metabolic rate, whereas a prolonged elevation of BAT activity improves insulin sensitivity. However, substantial reductions in body weight following BAT activation has not yet been shown in humans. This observation raise the possibility for feedback mechanisms in adult humans in terms of a brown fat-brain crosstalk, possibly mediated by batokines, factors produced by and secreted from brown fat. Batokines also seems to be involved in BAT recruitment by stimulating proliferation and differentiation of brown fat progenitors. Increasing human BAT capacity could thus include inducing brown fat biogenesis as well as identifying novel batokines. Another attractive approach would be to induce a brown fat phenotype, the so-called brite or beige fat, within the white fat depots. In adult humans, white fat tissue transformation into beige has been observed in patients with pheochromocytoma, a norepinephrine-producing tumor. Interestingly, human beige fat is predominantly induced in regions that were BAT during early childhood, possibly reflecting that a presence of human beige progenitors is depot specific and originating from BAT. In conclusion, to utilize the anti-obesity potential of human BAT focus should be directed towards identifying novel regulators of brown and beige fat progenitor cells, as well as feedback mechanisms of BAT activation. This would allow for identification of novel anti-obesity targets. Copyright © 2017. Published by Elsevier B.V.

  10. Endocrine-disrupting chemicals and obesity development in humans: A review

    DEFF Research Database (Denmark)

    Tang-Péronard, Jeanett; Andersen, Helle Raun; Jensen, Tina Kold

    2011-01-01

    This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The resu......This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans...... dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes...... predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors....

  11. Gender discrimination, gender disparities in obesity and human development

    OpenAIRE

    Ferretti, Fabrizio; Mariani, Michele

    2017-01-01

    Measuring gender inequality and women’s empowerment is essential to understand the determinants of gender gaps, evaluate policies and monitor countries’ progress. With this aim, over the past two decades, research has mainly been directed towards the development of composite indices. The purpose of this paper is to introduce a new and interdisciplinary perspective to the current debate on measuring gender inequality in human development. As a starting point, we develop a simple macroeconomic ...

  12. Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans.

    Science.gov (United States)

    Allen, Jacob M; Mailing, Lucy J; Niemiro, Grace M; Moore, Rachel; Cook, Marc D; White, Bryan A; Holscher, Hannah D; Woods, Jeffrey A

    2018-04-01

    Exercise is associated with altered gut microbial composition, but studies have not investigated whether the gut microbiota and associated metabolites are modulated by exercise training in humans. We explored the impact of 6 wk of endurance exercise on the composition, functional capacity, and metabolic output of the gut microbiota in lean and obese adults with multiple-day dietary controls before outcome variable collection. Thirty-two lean (n = 18 [9 female]) and obese (n = 14 [11 female]), previously sedentary subjects participated in 6 wk of supervised, endurance-based exercise training (3 d·wk) that progressed from 30 to 60 min·d and from moderate (60% of HR reserve) to vigorous intensity (75% HR reserve). Subsequently, participants returned to a sedentary lifestyle activity for a 6-wk washout period. Fecal samples were collected before and after 6 wk of exercise, as well as after the sedentary washout period, with 3-d dietary controls in place before each collection. β-diversity analysis revealed that exercise-induced alterations of the gut microbiota were dependent on obesity status. Exercise increased fecal concentrations of short-chain fatty acids in lean, but not obese, participants. Exercise-induced shifts in metabolic output of the microbiota paralleled changes in bacterial genes and taxa capable of short-chain fatty acid production. Lastly, exercise-induced changes in the microbiota were largely reversed once exercise training ceased. These findings suggest that exercise training induces compositional and functional changes in the human gut microbiota that are dependent on obesity status, independent of diet and contingent on the sustainment of exercise.

  13. The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans

    Directory of Open Access Journals (Sweden)

    Kasper W. ter Horst

    2017-11-01

    Conclusions: Fructose ingestion in obese humans stimulates FGF21 secretion, and this response is related to systemic metabolism. Further studies are needed to establish if FGF21 signaling is (pathophysiologically involved in fructose metabolism and metabolic health.

  14. Imaging methods for analyzing body composition in human obesity and cardiometabolic disease.

    Science.gov (United States)

    Seabolt, Lynn A; Welch, E Brian; Silver, Heidi J

    2015-09-01

    Advances in the technological qualities of imaging modalities for assessing human body composition have been stimulated by accumulating evidence that individual components of body composition have significant influences on chronic disease onset, disease progression, treatment response, and health outcomes. Importantly, imaging modalities have provided a systematic method for differentiating phenotypes of body composition that diverge from what is considered normal, that is, having low bone mass (osteopenia/osteoporosis), low muscle mass (sarcopenia), high fat mass (obesity), or high fat with low muscle mass (sarcopenic obesity). Moreover, advances over the past three decades in the sensitivity and quality of imaging not just to discern the amount and distribution of adipose and lean tissue but also to differentiate layers or depots within tissues and cells is enhancing our understanding of distinct mechanistic, metabolic, and functional roles of body composition within human phenotypes. In this review, we focus on advances in imaging technologies that show great promise for future investigation of human body composition and how they are being used to address the pandemic of obesity, metabolic syndrome, and diabetes. © 2015 New York Academy of Sciences.

  15. Food and drug reward: overlapping circuits in human obesity and addiction

    Energy Technology Data Exchange (ETDEWEB)

    Volkow N. D.; Wang G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.; Baler, R.

    2012-12-01

    Both drug addiction and obesity can be defined as disorders in which the saliency value of one type of reward (drugs and food, respectively) becomes abnormally enhanced relative to, and at the expense of others. This model is consistent with the fact that both drugs and food have powerful reinforcing effects - partly mediated by dopamine increases in the limbic system - that, under certain circumstances or in vulnerable individuals, could overwhelm the brain's homeostatic control mechanisms. Such parallels have generated significant interest in understanding the shared vulnerabilities and trajectories between addiction and obesity. Now, brain imaging discoveries have started to uncover common features between these two conditions and to delineate some of the overlapping brain circuits whose dysfunctions may explain stereotypic and related behavioral deficits in human subjects. These results suggest that both obese and drug addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning (memory/learning), impulse control (behavioral inhibition), stress reactivity and interoceptive awareness. Here, we integrate findings predominantly derived from positron emission tomography that investigate the role of dopamine in drug addiction and in obesity and propose an updated working model to help identify treatment strategies that may benefit both of these conditions.

  16. Practical Review of Recognition and Management of Obesity and Lipohypertrophy in Human Immunodeficiency Virus Infection.

    Science.gov (United States)

    Lake, Jordan E; Stanley, Takara L; Apovian, Caroline M; Bhasin, Shalendar; Brown, Todd T; Capeau, Jaqueline; Currier, Judith S; Dube, Michael P; Falutz, Julian; Grinspoon, Steven K; Guaraldi, Giovanni; Martinez, Esteban; McComsey, Grace A; Sattler, Fred R; Erlandson, Kristine M

    2017-05-15

    Obesity and lipohypertrophy are common in treated human immunodeficiency virus (HIV) infection and contribute to morbidity and mortality among HIV-infected adults on antiretroviral therapy (ART). We present a consensus opinion on the diagnosis, clinical consequences, and treatment of excess adiposity in adults with treated HIV infection. Obesity and lipohypertrophy commonly occur among HIV-infected adults on ART and may have overlapping pathophysiologies and/or synergistic metabolic consequences. Traditional, HIV-specific, and ART-specific risk factors all contribute. The metabolic and inflammatory consequences of excess adiposity are critical drivers of non-AIDS events in this population. Although promising treatment strategies exist, further research is needed to better understand the pathophysiology and optimal treatment of obesity and lipohypertrophy in the modern ART era. Both generalized obesity and lipohypertrophy are prevalent among HIV-infected persons on ART. Aggressive diagnosis and management are key to the prevention and treatment of end-organ disease in this population and critical to the present and future health of HIV-infected persons. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com

  17. Food and drug reward: overlapping circuits in human obesity and addiction

    International Nuclear Information System (INIS)

    Volkow, N.D.; Wang, G.J.; Fowler, J.S.; Tomasi, D.; Baler, R.

    2012-01-01

    Both drug addiction and obesity can be defined as disorders in which the saliency value of one type of reward (drugs and food, respectively) becomes abnormally enhanced relative to, and at the expense of others. This model is consistent with the fact that both drugs and food have powerful reinforcing effects - partly mediated by dopamine increases in the limbic system - that, under certain circumstances or in vulnerable individuals, could overwhelm the brain's homeostatic control mechanisms. Such parallels have generated significant interest in understanding the shared vulnerabilities and trajectories between addiction and obesity. Now, brain imaging discoveries have started to uncover common features between these two conditions and to delineate some of the overlapping brain circuits whose dysfunctions may explain stereotypic and related behavioral deficits in human subjects. These results suggest that both obese and drug addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning (memory/learning), impulse control (behavioral inhibition), stress reactivity and interoceptive awareness. Here, we integrate findings predominantly derived from positron emission tomography that investigate the role of dopamine in drug addiction and in obesity and propose an updated working model to help identify treatment strategies that may benefit both of these conditions.

  18. The evolution of human adiposity and obesity: where did it all go wrong?

    Directory of Open Access Journals (Sweden)

    Jonathan C. K. Wells

    2012-09-01

    Full Text Available Because obesity is associated with diverse chronic diseases, little attention has been directed to the multiple beneficial functions of adipose tissue. Adipose tissue not only provides energy for growth, reproduction and immune function, but also secretes and receives diverse signaling molecules that coordinate energy allocation between these functions in response to ecological conditions. Importantly, many relevant ecological cues act on growth and physique, with adiposity responding as a counterbalancing risk management strategy. The large number of individual alleles associated with adipose tissue illustrates its integration with diverse metabolic pathways. However, phenotypic variation in age, sex, ethnicity and social status is further associated with different strategies for storing and using energy. Adiposity therefore represents a key means of phenotypic flexibility within and across generations, enabling a coherent life-history strategy in the face of ecological stochasticity. The sensitivity of numerous metabolic pathways to ecological cues makes our species vulnerable to manipulative globalized economic forces. The aim of this article is to understand how human adipose tissue biology interacts with modern environmental pressures to generate excess weight gain and obesity. The disease component of obesity might lie not in adipose tissue itself, but in its perturbation by our modern industrialized niche. Efforts to combat obesity could be more effective if they prioritized ‘external’ environmental change rather than attempting to manipulate ‘internal’ biology through pharmaceutical or behavioral means.

  19. Metabolic regulation and the anti-obesity perspectives of human brown fat

    DEFF Research Database (Denmark)

    Scheele, Camilla; Nielsen, Søren

    2017-01-01

    is depot specific and originating from BAT. In conclusion, to utilize the anti-obesity potential of human BAT focus should be directed towards identifying novel regulators of brown and beige fat progenitor cells, as well as feedback mechanisms of BAT activation. This would allow for identification of novel...... shown in humans. This observation raise the possibility for feedback mechanisms in adult humans in terms of a brown fat-brain crosstalk, possibly mediated by batokines, factors produced by and secreted from brown fat. Batokines also seems to be involved in BAT recruitment by stimulating proliferation...... and differentiation of brown fat progenitors. Increasing human BAT capacity could thus include inducing brown fat biogenesis as well as identifying novel batokines. Another attractive approach would be to induce a brown fat phenotype, the so-called brite or beige fat, within the white fat depots. In adult humans...

  20. Serum Levels of 20-Kilodalton Human Growth Hormone (GH) in Children with Simple Obesity

    OpenAIRE

    Mayumi, Ishikawa; Naoko, Satou; Toru, Kikuchi; Makoto, Uchiyama; Noriyuki, Katsumata; Toshiaki, Tanaka; National Center for Child Health and Developmant:Toho Universit School of Medicine; National Research Institute for Child Health and Development; Niigata University; Niigata University; National Research Institute for Child Health and Development; National Center for Child Health and Developmant

    2003-01-01

    Twenty-kilodalton human GH, a human GH (hGH) variant, has insulin-like and anti-insulin-like actions different from 22-kilodalton hGH (22K). The diabetogenic action of twenty-kilodalton hGH (20K) is reported to be weaker than that of 22K, yet it is still unclear whether secretion of 20K is influenced by factors in carbohydrate metabolism. We measured serum 20K and 22K in children with simple obesity and studied the regulation of 20K production. The subject were 124 boys (9.78±1.94 yr old, bod...

  1. Obesity-related metabolic dysfunction in dogs: a comparison with human metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Tvarijonaviciute Asta

    2012-08-01

    Full Text Available Abstract Background Recently, metabolic syndrome (MS has gained attention in human metabolic medicine given its associations with development of type 2 diabetes mellitus and cardiovascular disease. Canine obesity is associated with the development of insulin resistance, dyslipidaemia, and mild hypertension, but the authors are not aware of any existing studies examining the existence or prevalence of MS in obese dogs. Thirty-five obese dogs were assessed before and after weight loss (median percentage loss 29%, range 10-44%. The diagnostic criteria of the International Diabetes Federation were modified in order to define canine obesity-related metabolic dysfunction (ORMD, which included a measure of adiposity (using a 9-point body condition score [BCS], systolic blood pressure, fasting plasma cholesterol, plasma triglyceride, and fasting plasma glucose. By way of comparison, total body fat mass was measured by dual-energy X-ray absorptiometry, whilst total adiponectin, fasting insulin, and high-sensitivity C-reactive protein (hsCRP were measured using validated assays. Results Systolic blood pressure (P = 0.008, cholesterol (P = 0.003, triglyceride (P = 0.018, and fasting insulin (P P = 0.001. However, hsCRP did not change with weight loss. Prior to weight loss, 7 dogs were defined as having ORMD, and there was no difference in total fat mass between these dogs and those who did not meet the criteria for ORMD. However, plasma adiponectin concentration was less (P = 0.031, and plasma insulin concentration was greater (P = 0.030 in ORMD dogs. Conclusions In this study, approximately 20% of obese dogs suffer from ORMD, and this is characterized by hypoadiponectinaemia and hyperinsulinaemia. These studies can form the basis of further investigations to determine path genetic mechanisms and the health significance for dogs, in terms of disease associations and outcomes of weight loss.

  2. Anti-obesity effects of resveratrol: comparison between animal models and humans.

    Science.gov (United States)

    Fernández-Quintela, Alfredo; Carpéné, Christian; Fernández, Maialen; Aguirre, Leixuri; Milton-Laskibar, Iñaki; Contreras, José; Portillo, Maria P

    2016-08-01

    The prevalence of obesity has increased rapidly during recent years and has reached epidemic proportions. As a result, the scientific community is interested in active biomolecules which are naturally present in plants and foodstuffs and may be useful in body weight management. In recent years, polyphenols have made up one of the most frequently studied groups among these molecules. Numerous studies have been carried out on animals to analyse the potential anti-obesity effects of resveratrol, a non-flavonoid polyphenol, and a general consensus concerning the body-fat-lowering effect of this compound exists. By contrast, studies in humans have been few so far. Moreover, in these studies, the effectiveness of resveratrol is low. The aims of the present review are to summarize the results reported so far on this topic and to justify the differences observed between animals and humans. It seems that the reduced response to resveratrol in humans cannot be attributed to the use of lower doses in humans because the doses that induce body-fat-lowering effects in rodents are in the same range as those used in human studies. With regard to the experimental period length, treatments were longer in animal studies than in human studies. This can be one of the reasons contributing to the reduced responses observed in humans. Moreover, animals used in the reported studies are young while volunteers participating in human studies are adults, suggesting that resveratrol may be more efficient in young individuals. In addition to differences in the experimental designs, metabolic differences between animals and human cannot be discarded.

  3. Human Adenovirus 36 Infection Increased the Risk of Obesity: A Meta-Analysis Update.

    Science.gov (United States)

    Xu, Mei-Yan; Cao, Bing; Wang, Dong-Fang; Guo, Jing-Hui; Chen, Kai-Li; Shi, Mai; Yin, Jian; Lu, Qing-Bin

    2015-12-01

    Human adenovirus 36 (HAdV-36), as the key pathogen, was supposed and discussed to be associated with obesity. We searched the references on the association between HAdV-36 infection and obesity with the different epidemiological methods, to explore the relationship with a larger sample size by meta-analysis and compare the differences of epidemiological methods and population subsets by the subgroup analyses.We conducted literature search on the association between HAdV-36 infections and obesity in English or Chinese published up to July 1, 2015. The primary outcome was the HAdV-36 infection rate in the obese and lean groups; the secondary outcomes were the BMI level and BMI z-score in the HAdV-36 positive and negative groups. The pooled odds ratio (OR) was calculated for the primary outcome; the standardized mean differences (SMDs) were calculated for the secondary and third outcomes. Prediction interval (PI) was graphically presented in the forest plot of the random effect meta-analyses. Metaregression analysis and subgroup analysis were performed.Finally 24 references with 10,191 study subjects were included in the meta-analysis. The obesity subjects were more likely to be infected with HAdV-36 compared to the lean controls (OR = 2.00; 95%CI: 1.46, 2.74; PI: 0.59, 6.76; P infection for obesity were 1.77 (95%CI: 1.19, 2.63; PI: 0.44, 7.03; P = 0.005) and 2.26 (95%CI: 1.67, 3.07; PI: 1.45, 3.54; P SMD of BMI was 0.28 (95% CI: 0.08, 0.47; PI: -0.53, 1.08; P = 0.006) in the HAdV-36 positive subjects with a high heterogeneity (I = 86.5%; P infection was higher than those without HAdV-36 infection (SMD = 0.19; 95%CI: -0.31, 0.70; PI: -2.10, 2.49), which had no significantly statistical difference (P = 0.453).HAdV-36 infection increased the risk of obesity. HAdV-36 also increased the risk of weight gain in adults, which was not observed in children.

  4. Proteomics analysis of human obesity reveals the epigenetic factor HDAC4 as a potential target for obesity.

    Directory of Open Access Journals (Sweden)

    Mohamed Abu-Farha

    Full Text Available Sedentary lifestyle and excessive energy intake are prominent contributors to obesity; a major risk factors for the development of insulin resistance, type 2 diabetes and cardiovascular diseases. Elucidating the molecular mechanisms underlying these chronic conditions is of relevant importance as it might lead to the identification of novel anti-obesity targets. The purpose of the current study is to investigate differentially expressed proteins between lean and obese subjects through a shot-gun quantitative proteomics approach using peripheral blood mononuclear cells (PBMCs extracts as well as potential modulation of those proteins by physical exercise. Using this approach, a total of 47 proteins showed at least 1.5 fold change between lean and obese subjects. In obese, the proteomic profiling before and after 3 months of physical exercise showed differential expression of 38 proteins. Thrombospondin 1 (TSP1 was among the proteins that were upregulated in obese subjects and then decreased by physical exercise. Conversely, the histone deacetylase 4 (HDAC4 was downregulated in obese subjects and then induced by physical exercise. The proteomic data was further validated by qRT-PCR, Western blot and immunohistochemistry in both PBMCs and adipose tissue. We also showed that HDAC4 levels correlated positively with maximum oxygen consumption (VO2 Max but negatively with body mass index, percent body fat, and the inflammatory chemokine RANTES. In functional assays, our data indicated that ectopic expression of HDAC4 significantly impaired TNF-α-dependent activation of NF-κB, establishing thus a link between HDAC4 and regulation of the immune system. Together, the expression pattern of HDAC4 in obese subjects before and after physical exercise, its correlation with various physical, clinical and metabolic parameters along with its inhibitory effect on NF-κB are suggestive of a protective role of HDAC4 against obesity. HDAC4 could therefore represent

  5. The Effects of Resveratrol Supplementation in Overweight and Obese Humans: A Systematic Review of Randomized Trials.

    Science.gov (United States)

    Christenson, Julia; Whitby, Serena J; Mellor, Duane; Thomas, Jackson; McKune, Andrew; Roach, Paul D; Naumovski, Nenad

    2016-09-01

    Obesity and metabolic syndrome are significant global health issues, with current public health messages predominately focused on altering dietary and physical activity behaviors. Resveratrol is a polyphenol (stilbenoid) commonly found in grapes, and human trials to date have shown conflicting and limited beneficial effects with respect to health. The aim of this study was to determine the effect of resveratrol supplementation on reducing body weight and modifying associated inflammatory markers. A systematic review was undertaken following the PRISMA guidelines and using five indexed databases (OVID MEDLINE, Cochrane Library, Web of Science, SCOPUS, and CINAHL). A search strategy was formulated to select randomized, double-blind, placebo-controlled human trials investigating the effects of resveratrol supplementation on obesity or overweight, including body weight, metabolic and inflammatory markers. Five thousand five hundred sixty-nine studies published from 1990 to November 2015 were identified, with only nine papers meeting the inclusion criteria. The studies involved 208 participants (aged 49.2 ± 8.3 years) and utilized a substantial range of resveratrol doses (75-3000 mg/day). Study durations were a minimum of 2 weeks (14-90 days). Seven studies indicated no significant change in body mass index or body weight (P > 0.05), and three studies showed no improvements in fat mass, fat volume, or abdominal fat distribution (P > 0.05). Four studies included measurements of inflammatory markers, with three of these finding resveratrol supplementation to have a significant positive effect (P > 0.05). Based on the included studies, there is currently insufficient evidence to support the recommendation of resveratrol supplements in management of obesity. However, there were significant but not entirely consistent anti-inflammatory effects after resveratrol supplementation in overweight and obese individuals.

  6. Stress, overeating, and obesity: Insights from human studies and preclinical models.

    Science.gov (United States)

    Razzoli, Maria; Pearson, Carolyn; Crow, Scott; Bartolomucci, Alessandro

    2017-05-01

    Eating disorders and obesity have become predominant in human society. Their association to modern lifestyle, encompassing calorie-rich diets, psychological stress, and comorbidity with major diseases are well documented. Unfortunately the biological basis remains elusive and the pharmacological treatment inadequate, in part due to the limited availability of valid animal models. Human research on binge eating disorder (BED) proves a strong link between stress exposure and bingeing: state-levels of stress and negative affect are linked to binge eating in individuals with BED both in laboratory settings and the natural environment. Similarly, classical animal models of BED reveal an association between acute exposure to stressors and binging but they are often associated with unchanged or decreased body weight, thus reflecting a negative energy balance, which is uncommon in humans where most commonly BED is associated with excessive or unstable body weight gain. Recent mouse models of subordination stress induce spontaneous binging and hyperphagia, altogether more closely mimicking the behavioral and metabolic features of human BED. Therefore the translational relevance of subordination stress models could facilitate the identification of the neurobiological basis of BED and obesity-associated disease and inform on the development of innovative therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Male Obesity.

    Science.gov (United States)

    Kiess, Wieland; Wagner, Isabel V; Kratzsch, Jürgen; Körner, Antje

    2015-12-01

    Many cross-sectional analyses and longitudinal studies have examined the association between adiposity and pubertal development. In addition, the impact of an increased fat mass on reproduction and fertility in human obese men and in male animal models of obesity has been studied. A trend toward earlier pubertal development and maturation in both sexes has been shown, and the notion that obese boys might progress to puberty at a slower pace than their nonobese peers can no longer be substantiated. Impaired fertility markers and reduced reproductive functions have been observed in obesity. Obesity affects both pubertal development and fertility in men. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Circulating Blood Monocyte Subclasses and Lipid-Laden Adipose Tissue Macrophages in Human Obesity.

    Directory of Open Access Journals (Sweden)

    Tal Pecht

    Full Text Available Visceral adipose tissue foam cells are increased in human obesity, and were implicated in adipose dysfunction and increased cardio-metabolic risk. In the circulation, non-classical monocytes (NCM are elevated in obesity and associate with atherosclerosis and type 2 diabetes. We hypothesized that circulating NCM correlate and/or are functionally linked to visceral adipose tissue foam cells in obesity, potentially providing an approach to estimate visceral adipose tissue status in the non-surgical obese patient.We preformed ex-vivo functional studies utilizing sorted monocyte subclasses from healthy donors. Moreover, we assessed circulating blood monocyte subclasses and visceral fat adipose tissue macrophage (ATM lipid content by flow-cytometry in paired blood and omental-fat samples collected from patients (n = 65 undergoing elective abdominal surgery.Ex-vivo, NCM and NCM-derived macrophages exhibited lower lipid accumulation capacity compared to classical or intermediate monocytes/-derived macrophages. Moreover, of the three subclasses, NCM exhibited the lowest migration towards adipose tissue conditioned-media. In a cohort of n = 65, increased %NCM associated with higher BMI (r = 0.250,p<0.05 and ATM lipid content (r = 0.303,p<0.05. Among patients with BMI≥25Kg/m2, linear regression models adjusted for age, sex or BMI revealed that NCM independently associate with ATM lipid content, particularly in men.Collectively, although circulating blood NCM are unlikely direct functional precursor cells for adipose tissue foam cells, their increased percentage in the circulation may clinically reflect higher lipid content in visceral ATMs.

  9. Methods for quantifying adipose tissue insulin resistance in overweight/obese humans.

    Science.gov (United States)

    Ter Horst, K W; van Galen, K A; Gilijamse, P W; Hartstra, A V; de Groot, P F; van der Valk, F M; Ackermans, M T; Nieuwdorp, M; Romijn, J A; Serlie, M J

    2017-08-01

    Insulin resistance of adipose tissue is an important feature of obesity-related metabolic disease. However, assessment of lipolysis in humans requires labor-intensive and expensive methods, and there is limited validation of simplified measurement methods. We aimed to validate simplified methods for the quantification of adipose tissue insulin resistance against the assessment of insulin sensitivity of lipolysis suppression during hyperinsulinemic-euglycemic clamp studies. We assessed the insulin-mediated suppression of lipolysis by tracer-dilution of [1,1,2,3,3- 2 H 5 ]glycerol during hyperinsulinemic-euglycemic clamp studies in 125 overweight or obese adults (85 men, 40 women; age 50±11 years; body mass index 38±7 kg m -2 ). Seven indices of adipose tissue insulin resistance were validated against the reference measurement method. Low-dose insulin infusion resulted in suppression of the glycerol rate of appearance ranging from 4% (most resistant) to 85% (most sensitive), indicating a good range of adipose tissue insulin sensitivity in the study population. The reference method correlated with (1) insulin-mediated suppression of plasma glycerol concentrations (r=0.960, PInsulin Resistance (Adipo-IR) index (fasting plasma insulin-NEFA product; r=-0.526, Pinsulin-glycerol product (r=-0.467, PInsulin Resistance Index (fasting plasma insulin-basal lipolysis product; r=0.460, PInsulin Sensitivity Check Index (QUICKI)-NEFA index (r=0.621, Pinsulin resistance (area under the curve ⩾0.801, Pinsulin sensitivity (that is, the antilipolytic action of insulin) can be reliably quantified in overweight and obese humans by simplified index methods. The sensitivity and specificity of the Adipo-IR index and the fasting plasma insulin-glycerol product, combined with their simplicity and acceptable agreement, suggest that these may be most useful in clinical practice.

  10. Naltrexone and human eating behavior: a dose-ranging inpatient trial in moderately obese men.

    Science.gov (United States)

    Maggio, C A; Presta, E; Bracco, E F; Vasselli, J R; Kissileff, H R; Pfohl, D N; Hashim, S A

    1985-06-01

    To investigate the effects of the long-acting opiate antagonist naltrexone on spontaneous human eating behavior, eight moderately obese male paid volunteers were housed in a hospital metabolic unit for 28 days and offered palatable foods ad lib by a platter service method. Under double-blind conditions, equally divided doses of 100, 200 and 300 mg naltrexone, or an acetaminophen placebo, were administered twice daily in tablet form for 3-day periods each, according to a Latin Square design. The doses of naltrexone resulted in decreases of daily caloric intake from placebo level, but these reductions were neither statistically significant nor dose-related. When the averaged effects of the doses were compared to placebo, five subjects showed intake reductions but the overall intake reduction of 301.5 +/- 198.1 kcal/day (mean +/- SEM) was not statistically significant. Naltrexone administration failed to selectively alter intakes of individual meals and snacks or macronutrient consumption patterns. During active drug periods, subjects lost 0.62 +/- 0.22 lb over 3 days, while during the placebo period, subjects gained 0.46 +/- 0.68 lb. However, there was no reliable change of basal metabolic rate as a function of naltrexone administration. The present results, which indicate that naltrexone administration is relatively ineffective in reducing food intake and inducing body weight loss in obese humans, are thus in contrast with reports that administration of opiate antagonist agents promote significant reductions of food intake and attenuations of body weight gain in experimental animals.

  11. Human Obesity Associated with an Intronic SNP in the Brain-Derived Neurotrophic Factor Locus

    Directory of Open Access Journals (Sweden)

    Zongyang Mou

    2015-11-01

    Full Text Available Brain-derived neurotrophic factor (BDNF plays a key role in energy balance. In population studies, SNPs of the BDNF locus have been linked to obesity, but the mechanism by which these variants cause weight gain is unknown. Here, we examined human hypothalamic BDNF expression in association with 44 BDNF SNPs. We observed that the minor C allele of rs12291063 is associated with lower human ventromedial hypothalamic BDNF expression (p < 0.001 and greater adiposity in both adult and pediatric cohorts (p values < 0.05. We further demonstrated that the major T allele for rs12291063 possesses a binding capacity for the transcriptional regulator, heterogeneous nuclear ribonucleoprotein D0B, knockdown of which disrupts transactivation by the T allele. Binding and transactivation functions are both disrupted by substituting C for T. These findings provide a rationale for BDNF augmentation as a targeted treatment for obesity in individuals who have the rs12291063 CC genotype.

  12. Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7

    Energy Technology Data Exchange (ETDEWEB)

    Duggirala, R.; Stern, M.P.; Reinhart, L.J. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

    1996-09-01

    Despite the evidence that human obesity has strong genetic determinants, efforts at identifying specific genes that influence human obesity have largely been unsuccessful. Using the sibship data obtained from 32 low-income Mexican American pedigrees ascertained on a type II diabetic proband and a multipoint variance-components method, we tested for linkage between various obesity-related traits plus associated metabolic traits and 15 markers on human chromosome 7. We found evidence for linkage between markers in the OB gene region and various traits, as follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1 (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514 explained 56% of the total phenotypic variation in extremity skinfolds. Variation at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and {approximately}73% of phenotypic variation in split proinsulin concentration, respectively. Weaker evidence for linkage to several other obesity-related traits (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was observed for a genetic location, which is {approximately}15 cM telomeric to OB. In conclusion, our study reveals that the OB region plays a significant role in determining the phenotypic variation of both insulin precursors and obesity-related traits, at least in Mexican Americans. 66 refs., 3 figs., 4 tabs.

  13. Obesity associated advanced glycation end products within the human uterine cavity adversely impact endometrial function and embryo implantation competence.

    Science.gov (United States)

    Antoniotti, Gabriella S; Coughlan, Melinda; Salamonsen, Lois A; Evans, Jemma

    2018-04-01

    Do obese levels of advanced glycation end products (AGEs) within the uterine cavity detrimentally alter tissue function in embryo implantation and placental development? Obese levels of AGEs activate inflammatory signaling (p65 NFκB) within endometrial epithelial cells and alter their function, cause endoplasmic reticulum (ER) stress in endometrial stromal cells and impair decidualization, compromise implantation of blastocyst mimics and inhibit trophoblast invasion. Obese women experience a higher incidence of infertility, recurrent miscarriage and pregnancy complications compared with lean women. Oocyte donation cycles suggest a detrimental uterine environment plays a role in these outcomes. Uterine lavage and tissues from lean (BMI 19.5-24.9, n = 17) and obese (BMI > 30, n = 16) women examined. Cell culture experiments utilizing human endometrial epithelial, trophectoderm and trophoblast cell lines and primary human stromal cells used to examine the functional impact of obese levels of AGEs. Levels of AGEs examined within uterine lavage assessed by ELISA to determine differences between lean and obese women. Expression and localization of AGEs, receptor for AGEs (RAGE) and NFκB within endometrial tissues obtained from lean and obese women determined by immunohistochemistry. Endometrial epithelial cells (ECC-1), primary human stromal cells and trophoblast cells (HTR8-SVneo) treated with lean (2000 nmol/mol lysine) or obese (8000 nmol/mol lysine) uterine levels of AGEs and p65 NFκB (western immunoblot), real-time adhesion, proliferation migration and invasion (xCelligence real-time cell function analysis), decidualization (cell morphology and prolactin release), ER stress (western immunoblot for p-PERK) determined. Co-cultures of endometrial epithelial cells and blastocyst mimics (trophectoderm spheroids) similarly treated with lean or obese uterine levels of AGEs to determine their impact on embryo implantation. AGEs were significantly elevated (P = 0

  14. 11Beta-HSD type 1 expression in human adipose tissue: impact of gender, obesity, and fat localization

    DEFF Research Database (Denmark)

    Paulsen, Søren Kildeberg; Pedersen, Steen Bønløkke; Fisker, Sanne

    2007-01-01

    of the metabolic syndrome. Our objective was to compare 11beta-HSD1 gene expression in different fat depots (visceral, subcutaneous abdominal, and subcutaneous gluteal) in lean and obese men and women. RESEARCH METHODS AND PROCEDURES: A cross-sectional study design was used for healthy patients undergoing minor...... women had lower 11beta-HSD1 gene expression in subcutaneous adipose tissue compared with men (62% lower, p difference was found between obese men and women. 11Beta-HSD1 mRNA in human adipose tissue was higher in obese subjects compared with lean subjects in both women...... and men and in both subcutaneous and visceral adipose tissue. No difference in mRNA expression of 11beta-HSD1 between visceral and subcutaneous adipose tissue or between subcutaneous adipose tissue from different depots was found. CONCLUSIONS: 11Beta-HSD1 in adipose tissue is increased in obesity in both...

  15. Genetic variants influencing effectiveness of exercise training programmes in obesity - an overview of human studies.

    Science.gov (United States)

    Leońska-Duniec, A; Ahmetov, I I; Zmijewski, P

    2016-09-01

    Frequent and regular physical activity has significant benefits for health, including improvement of body composition and help in weight control. Consequently, promoting training programmes, particularly in those who are genetically predisposed, is a significant step towards controlling the presently increasing epidemic of obesity. Although the physiological responses of the human body to exercise are quite well described, the genetic background of these reactions still remains mostly unknown. This review not only summarizes the current evidence, through a literature review and the results of our studies on the influence of gene variants on the characteristics and range of the body's adaptive response to training, but also explores research organization problems, future trends, and possibilities. We describe the most reliable candidate genetic markers that are involved in energy balance pathways and body composition changes in response to training programmes, such as FTO, MC4R, ACE, PPARG, LEP, LEPR, ADRB2, and ADRB3. This knowledge can have an enormous impact not only on individualization of exercise programmes to make them more efficient and safer, but also on improved recovery, traumatology, medical care, diet, supplementation and many other areas. Nevertheless, the current studies still represent only the first steps towards a better understanding of the genetic factors that influence obesity-related traits, as well as gene variant x physical activity interactions, so further research is necessary.

  16. Hepatic energy metabolism in human diabetes mellitus, obesity and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Koliaki, Chrysi; Roden, Michael

    2013-10-15

    Alterations of hepatic mitochondrial function have been observed in states of insulin resistance and non-alcoholic fatty liver disease (NAFLD). Patients with overt type 2 diabetes mellitus (T2DM) can exhibit reduction in hepatic adenosine triphosphate (ATP) synthesis and impaired repletion of their hepatic ATP stores upon ATP depletion by fructose. Obesity and NAFLD may also associate with impaired ATP recovery after ATP-depleting challenges and augmented oxidative stress in the liver. On the other hand, patients with obesity or NAFLD can present with upregulated hepatic anaplerotic and oxidative fluxes, including β-oxidation and tricarboxylic cycle activity. The present review focuses on the methods and data on hepatic energy metabolism in various states of human insulin resistance. We propose that the liver can adapt to increased lipid exposition by greater lipid storing and oxidative capacity, resulting in increased oxidative stress, which in turn could deteriorate hepatic mitochondrial function in chronic insulin resistance and NAFLD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Favorable Vascular Actions of Angiotensin-(1-7) in Human Obesity.

    Science.gov (United States)

    Schinzari, Francesca; Tesauro, Manfredi; Veneziani, Augusto; Mores, Nadia; Di Daniele, Nicola; Cardillo, Carmine

    2018-01-01

    Obese patients have vascular dysfunction related to impaired insulin-stimulated vasodilation and increased endothelin-1-mediated vasoconstriction. In contrast to the harmful vascular actions of angiotensin (Ang) II, the angiotensin-converting enzyme 2 product Ang-(1-7) has shown to exert cardiovascular and metabolic benefits in experimental models through stimulation of the Mas receptor. We, therefore, examined the effects of exogenous Ang-(1-7) on vasodilator tone and endothelin-1-dependent vasoconstriction in obese patients. Intra-arterial infusion of Ang-(1-7) (10 nmol/min) resulted in significant increase in unstimulated forearm flow ( P =0.03), an effect that was not affected by the Mas receptor antagonist A779 (10 nmol/min; P >0.05). In the absence of hyperinsulinemia, however, forearm flow responses to graded doses of acetylcholine and sodium nitroprusside were not different during Ang-(1-7) administration compared with saline (both P >0.05). During infusion of regular insulin (0.15 mU/kg per minute), by contrast, endothelium-dependent vasodilator response to acetylcholine was significantly enhanced by Ang-(1-7) ( P =0.04 versus saline), whereas endothelium-independent response to sodium nitroprusside was not modified ( P =0.91). Finally, Ang-(1-7) decreased the vasodilator response to endothelin A receptor blockade (BQ-123; 10 nmol/min) compared with saline (6±1% versus 93±17%; P <0.001); nitric oxide inhibition by l- N -monomethylarginine (4 µmol/min) during concurrent endothelin A antagonism resulted in similar vasoconstriction in the absence or presence of Ang-(1-7 Ang-(1-7) ( P =0.69). Our findings indicate that in obese patients Ang-(1-7) has favorable effects not only to improve insulin-stimulated endothelium-dependent vasodilation but also to blunt endothelin-1-dependent vasoconstrictor tone. These findings provide support for targeting Ang-(1-7) to counteract the hemodynamic abnormalities of human obesity. © 2017 American Heart Association, Inc.

  18. Human intestinal microbiota composition is associated with local and systemic inflammation in obesity

    NARCIS (Netherlands)

    Verdam, F.J.; Fuentes Enriquez de Salamanca, S.; Jonge, de C.; Zoetendal, E.G.; Erbil, R.; Greve, J.W.; Buurman, W.A.; Vos, de W.M.; Rensen, S.S.

    2013-01-01

    OBJECTIVE: Intestinal microbiota have been suggested to contribute to the development of obesity, but the mechanism remains elusive. The relationship between microbiota composition, intestinal permeability, and inflammation in nonobese and obese subjects was investigated. DESIGN AND METHODS: Fecal

  19. Ethnic and population differences in the genetic predisposition to human obesity.

    Science.gov (United States)

    Stryjecki, C; Alyass, A; Meyre, D

    2018-01-01

    Obesity rates have escalated to the point of a global pandemic with varying prevalence across ethnic groups. These differences are partially explained by lifestyle factors in addition to genetic predisposition to obesity. This review provides a comprehensive examination of the ethnic differences in the genetic architecture of obesity. Using examples from evolution, heritability, admixture, monogenic and polygenic studies of obesity, we provide explanations for ethnic differences in the prevalence of obesity. The debate over definitions of race and ethnicity, the advantages and limitations of multi-ethnic studies and future directions of research are also discussed. Multi-ethnic studies have great potential to provide a better understanding of ethnic differences in the prevalence of obesity that may result in more targeted and personalized obesity treatments. © 2017 World Obesity Federation.

  20. Lysophosphatidic acid receptor mRNA levels in heart and white adipose tissue are associated with obesity in mice and humans.

    Directory of Open Access Journals (Sweden)

    Amy Brown

    Full Text Available Lysophosphatidic acid (LPA receptor signaling has been implicated in cardiovascular and obesity-related metabolic disease. However, the distribution and regulation of LPA receptors in the myocardium and adipose tissue remain unclear.This study aimed to characterize the mRNA expression of LPA receptors (LPA1-6 in the murine and human myocardium and adipose tissue, and its regulation in response to obesity.LPA receptor mRNA levels were determined by qPCR in i heart ventricles, isolated cardiomyocytes, and perigonadal adipose tissue from chow or high fat-high sucrose (HFHS-fed male C57BL/6 mice, ii 3T3-L1 adipocytes and HL-1 cardiomyocytes under conditions mimicking gluco/lipotoxicity, and iii human atrial and subcutaneous adipose tissue from non-obese, pre-obese, and obese cardiac surgery patients.LPA1-6 were expressed in myocardium and white adipose tissue from mice and humans, except for LPA3, which was undetectable in murine adipocytes and human adipose tissue. Obesity was associated with increased LPA4, LPA5 and/or LPA6 levels in mice ventricles and cardiomyocytes, HL-1 cells exposed to high palmitate, and human atrial tissue. LPA4 and LPA5 mRNA levels in human atrial tissue correlated with measures of obesity. LPA5 mRNA levels were increased in HFHS-fed mice and insulin resistant adipocytes, yet were reduced in adipose tissue from obese patients. LPA4, LPA5, and LPA6 mRNA levels in human adipose tissue were negatively associated with measures of obesity and cardiac surgery outcomes. This study suggests that obesity leads to marked changes in LPA receptor expression in the murine and human heart and white adipose tissue that may alter LPA receptor signaling during obesity.

  1. First manic episode associated with use of human chorionic gonadotropin for obesity: a case report.

    Science.gov (United States)

    Sanches, Marsal; Pigott, Teresa; Swann, Alan C; Soares, Jair C

    2014-03-01

    Although highly controversial, the treatment of obesity with exogenous human chorionic gonadotropin (HCG) remains popular in the USA. We report the case of a patient whose first manic episode was associated with the use of HCG for weight loss. A 32-year-old female patient was admitted to our psychiatric inpatient unit due to a two-week history of manic symptoms. She had no previous history of manic or hypomanic episodes and had completed a 45-day course of sublingual HCG for weight loss immediately prior to the onset of the manic episode. The patient was treated with lithium carbonate and aripiprazole, and progressed with improvement in the symptoms. While it is not possible to definitively link the HCG use to the development of mania, available evidence suggests that HCG may have a contributing role in triggering manic symptomatology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. The effect of obesity and repeated exposure on pharmacokinetic response to grape polyphenols in humans

    Science.gov (United States)

    Obesity is associated with lower circulating nutrients, though the reason is unclear. Since obesity may affect intestinal function, differential absorption may play a role. We investigated the pharmacokinetic response of polyphenols in obese/overweight and lean individuals from a dose of grape poly...

  3. Olfactory receptor genes cooperate with protocadherin genes in human extreme obesity

    NARCIS (Netherlands)

    Mariman, E.C.; Szklarczyk, R.J.; Bouwman, F.G.; Aller, E.E.; Baak, M.A. van; Wang, P.

    2015-01-01

    Worldwide, the incidence of obesity has increased dramatically over the past decades. More knowledge about the complex etiology of obesity is needed in order to find additional approaches for treatment and prevention. Investigating the exome sequencing data of 30 extremely obese subjects (BMI 45-65

  4. Functional Relationship between Obesity and Male Reproduction: from Humans to Animal Models

    NARCIS (Netherlands)

    Teerds, K.J.; Rooij, de D.G.; Keijer, J.

    2011-01-01

    BACKGROUND: The increase in the incidence of obesity has a substantial societal health impact. Contrasting reports have been published on whether overweight and obesity affect male fertility. To clarify this, we have reviewed published data on the relation between overweight/obesity, semen

  5. Renal hyperfiltration related to diabetes mellitus and obesity in human disease.

    Science.gov (United States)

    Sasson, Alexa N; Cherney, David Zi

    2012-01-15

    High intraglomerular pressure is associated with renal hyperfiltration, leading to the initiation and progression of kidney disease in experimental models of diabetes mellitus (DM). In humans, hyperfiltration is observed in patients with type 1 and type 2 DM, and is also seen in patients with pre-diabetic conditions, such as the metabolic syndrome. From a mechanistic perspective, both vascular and tubular factors likely contribute to the pathogenesis of hyperfiltration. Until now, human studies have primarily focused on the use of medications that inhibit the renin angiotensin system to reduce efferent vasoconstriction and thereby improve hyperfiltration. More recent advances in the development of investigational adenosine antagonists and inhibitors of sodium glucose co-transport may help to elucidate tubular factors that contribute to afferent vasodilatation. In this review, we summarize available data from experimental and human studies of type 1 and type 2 DM and obesity to provide an overview of factors that contribute to the hyperfiltration state. We have focused on the renin angiotensin system, cyclooxygenase-2 system, nitric oxide, protein kinase C and endothelin as vascular determinants of hyperfiltration. We also discuss relevant tubular factors, since experimental models have suggested that inhibition of sodium-glucose cotransport may be renoprotective.

  6. Plasma endocannabinoid levels in lean, overweight and obese humans: relationships with intestinal permeability markers, inflammation and incretin secretion.

    Science.gov (United States)

    Little, Tanya J; Cvijanovic, Nada; DiPatrizio, Nicholas V; Argueta, Donovan A; Rayner, Christopher K; Feinle-Bisset, Christine; Young, Richard L

    2018-02-13

    Intestinal production of endocannabinoid and oleoylethanolamide (OEA) is impaired in high-fat diet/obese rodents, leading to reduced satiety. Such diets also alter the intestinal microbiome in association with enhanced intestinal permeability and inflammation, however little is known of these effects in humans. This study aimed to: (i) evaluate effects of lipid on plasma anandamide (AEA), 2-arachidonyl-sn-glycerol (2-AG) and OEA in humans, and (ii) examine relationships with intestinal permeability, inflammation markers and incretin hormone secretion. 20 lean, 18 overweight and 19 obese participants underwent intraduodenal Intralipid® infusion (2 kcal/min) with collection of endoscopic duodenal biopsies and blood. Plasma AEA, 2-AG, and OEA (HPLC/tandem mass spectrometry), tumour necrosis factor-α (TNF-α), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) (multiplex), and duodenal expression of occludin, zona-occludin-1 (ZO-1), intestinal-alkaline-phosphatase (IAP), and toll-like receptor-4 (TLR4) (RT-PCR), were assessed. Fasting plasma AEA was increased in obese, compared with lean and overweight (Plean (Plean and overweight. The relationships between plasma AEA with duodenal ZO-1 and IAP, and GIP, suggest that altered endocannabinoid signalling may contribute to changes in intestinal permeability, inflammation and incretin release in human obesity.

  7. Persistent organic pollutant levels in human visceral and subcutaneous adipose tissue in obese individuals—Depot differences and dysmetabolism implications

    Energy Technology Data Exchange (ETDEWEB)

    Pestana, Diogo, E-mail: diogopestana@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Centro de Investigação Médica, P-4200-450 Porto (Portugal); CINTESIS—Center for Research in Health Technologies and Information Systems, P-4200-450 Porto (Portugal); Faria, Gil [General Surgery Department, S. João Hospital, Faculty of Medicine, University of Porto, P-4200-450 Porto (Portugal); Sá, Carla [Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Centro de Investigação Médica, P-4200-450 Porto (Portugal); Fernandes, Virgínia C. [Chemistry Investigation Centre (CIQ), Department of Chemistry, Faculty of Sciences, University of Porto, P-4169-007 Porto (Portugal); Requimte—Instituto Superior de Engenharia, Instituto Politécnico do Porto, P-4200-072 Porto (Portugal); Teixeira, Diana; Norberto, Sónia [Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Centro de Investigação Médica, P-4200-450 Porto (Portugal); Faria, Ana [Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Centro de Investigação Médica, P-4200-450 Porto (Portugal); Chemistry Investigation Centre (CIQ), Department of Chemistry, Faculty of Sciences, University of Porto, P-4169-007 Porto (Portugal); Faculty of Nutrition and Food Sciences, University of Porto, P-4200-465 Porto (Portugal); and others

    2014-08-15

    Background: The role of persistent organic pollutants (POPs) with endocrine disrupting activity in the aetiology of obesity and other metabolic dysfunctions has been recently highlighted. Adipose tissue (AT) is a common site of POPs accumulation where they can induce adverse effects on human health. Objectives: To evaluate the presence of POPs in human visceral (vAT) and subcutaneous (scAT) adipose tissue in a sample of Portuguese obese patients that underwent bariatric surgery, and assess their putative association with metabolic disruption preoperatively, as well as with subsequent body mass index (BMI) reduction. Methods: AT samples (n=189) from obese patients (BMI ≥35) were collected and the levels of 13 POPs were determined by gas chromatography with electron-capture detection (GC-ECD). Anthropometric and biochemical data were collected at the time of surgery. BMI variation was evaluated after 12 months and adipocyte size was measured in AT samples. Results: Our data confirm that POPs are pervasive in this obese population (96.3% of detection on both tissues), their abundance increasing with age (R{sub S}=0.310, p<0.01) and duration of obesity (R{sub S}=0.170, p<0.05). We observed a difference in AT depot POPs storage capability, with higher levels of ΣPOPs in vAT (213.9±204.2 compared to 155.1±147.4 ng/g of fat, p<0.001), extremely relevant when evaluating their metabolic impact. Furthermore, there was a positive correlation between POP levels and the presence of metabolic syndrome components, namely dysglycaemia and hypertension, and more importantly with cardiovascular risk (R{sub S}=0.277, p<0.01), with relevance for vAT (R{sub S}=0.315, p<0.01). Finally, we observed an interesting relation of higher POP levels with lower weight loss in older patients. Conclusion: Our sample of obese subjects allowed us to highlight the importance of POPs stored in AT on the development of metabolic dysfunction in a context of obesity, shifting the focus to their

  8. Persistent organic pollutant levels in human visceral and subcutaneous adipose tissue in obese individuals—Depot differences and dysmetabolism implications

    International Nuclear Information System (INIS)

    Pestana, Diogo; Faria, Gil; Sá, Carla; Fernandes, Virgínia C.; Teixeira, Diana; Norberto, Sónia; Faria, Ana

    2014-01-01

    Background: The role of persistent organic pollutants (POPs) with endocrine disrupting activity in the aetiology of obesity and other metabolic dysfunctions has been recently highlighted. Adipose tissue (AT) is a common site of POPs accumulation where they can induce adverse effects on human health. Objectives: To evaluate the presence of POPs in human visceral (vAT) and subcutaneous (scAT) adipose tissue in a sample of Portuguese obese patients that underwent bariatric surgery, and assess their putative association with metabolic disruption preoperatively, as well as with subsequent body mass index (BMI) reduction. Methods: AT samples (n=189) from obese patients (BMI ≥35) were collected and the levels of 13 POPs were determined by gas chromatography with electron-capture detection (GC-ECD). Anthropometric and biochemical data were collected at the time of surgery. BMI variation was evaluated after 12 months and adipocyte size was measured in AT samples. Results: Our data confirm that POPs are pervasive in this obese population (96.3% of detection on both tissues), their abundance increasing with age (R S =0.310, p<0.01) and duration of obesity (R S =0.170, p<0.05). We observed a difference in AT depot POPs storage capability, with higher levels of ΣPOPs in vAT (213.9±204.2 compared to 155.1±147.4 ng/g of fat, p<0.001), extremely relevant when evaluating their metabolic impact. Furthermore, there was a positive correlation between POP levels and the presence of metabolic syndrome components, namely dysglycaemia and hypertension, and more importantly with cardiovascular risk (R S =0.277, p<0.01), with relevance for vAT (R S =0.315, p<0.01). Finally, we observed an interesting relation of higher POP levels with lower weight loss in older patients. Conclusion: Our sample of obese subjects allowed us to highlight the importance of POPs stored in AT on the development of metabolic dysfunction in a context of obesity, shifting the focus to their metabolic effects

  9. Human muscle fiber type-specific insulin signaling: impact of obesity and type 2 diabetes.

    Science.gov (United States)

    Albers, Peter H; Pedersen, Andreas J T; Birk, Jesper B; Kristensen, Dorte E; Vind, Birgitte F; Baba, Otto; Nøhr, Jane; Højlund, Kurt; Wojtaszewski, Jørgen F P

    2015-02-01

    Skeletal muscle is a heterogeneous tissue composed of different fiber types. Studies suggest that insulin-mediated glucose metabolism is different between muscle fiber types. We hypothesized that differences are due to fiber type-specific expression/regulation of insulin signaling elements and/or metabolic enzymes. Pools of type I and II fibers were prepared from biopsies of the vastus lateralis muscles from lean, obese, and type 2 diabetic subjects before and after a hyperinsulinemic-euglycemic clamp. Type I fibers compared with type II fibers have higher protein levels of the insulin receptor, GLUT4, hexokinase II, glycogen synthase (GS), and pyruvate dehydrogenase-E1α (PDH-E1α) and a lower protein content of Akt2, TBC1 domain family member 4 (TBC1D4), and TBC1D1. In type I fibers compared with type II fibers, the phosphorylation response to insulin was similar (TBC1D4, TBC1D1, and GS) or decreased (Akt and PDH-E1α). Phosphorylation responses to insulin adjusted for protein level were not different between fiber types. Independently of fiber type, insulin signaling was similar (TBC1D1, GS, and PDH-E1α) or decreased (Akt and TBC1D4) in muscle from patients with type 2 diabetes compared with lean and obese subjects. We conclude that human type I muscle fibers compared with type II fibers have a higher glucose-handling capacity but a similar sensitivity for phosphoregulation by insulin. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  10. Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue

    Directory of Open Access Journals (Sweden)

    Ribeiro Ricardo

    2012-09-01

    Full Text Available Abstract Background Periprostatic (PP adipose tissue surrounds the prostate, an organ with a high predisposition to become malignant. Frequently, growing prostatic tumor cells extend beyond the prostatic organ towards this fat depot. This study aimed to determine the genome-wide expression of genes in PP adipose tissue in obesity/overweight (OB/OW and prostate cancer patients. Methods Differentially expressed genes in human PP adipose tissue were identified using microarrays. Analyses were conducted according to the donors' body mass index characteristics (OB/OW versus lean and prostate disease (extra prostatic cancer versus organ confined prostate cancer versus benign prostatic hyperplasia. Selected genes with altered expression were validated by real-time PCR. Ingenuity Pathway Analysis (IPA was used to investigate gene ontology, canonical pathways and functional networks. Results In the PP adipose tissue of OB/OW subjects, we found altered expression of genes encoding molecules involved in adipogenic/anti-lipolytic, proliferative/anti-apoptotic, and mild immunoinflammatory processes (for example, FADS1, down-regulated, and LEP and ANGPT1, both up-regulated. Conversely, in the PP adipose tissue of subjects with prostate cancer, altered genes were related to adipose tissue cellular activity (increased cell proliferation/differentiation, cell cycle activation and anti-apoptosis, whereas a downward impact on immunity and inflammation was also observed, mostly related to the complement (down-regulation of CFH. Interestingly, we found that the microRNA MIRLET7A2 was overexpressed in the PP adipose tissue of prostate cancer patients. Conclusions Obesity and excess adiposity modified the expression of PP adipose tissue genes to ultimately foster fat mass growth. In patients with prostate cancer the expression profile of PP adipose tissue accounted for hypercellularity and reduced immunosurveillance. Both findings may be liable to promote a favorable

  11. Functional Profiles of Human Umbilical Cord-Derived Adult Mesenchymal Stem Cells in Obese/Diabetic Versus Healthy Women.

    Science.gov (United States)

    Montanucci, Pia; Pescara, Teresa; Pennoni, Ilaria; Alunno, Alessia; Bistoni, Onelia; Torlone, Elisabetta; Luca, Giovanni; Gerli, Roberto; Basta, Giuseppe; Calafiore, Riccardo

    2016-06-28

    Adult human mesenchymal stem cells retrieved, from the post-partum human umbilical cord Wharton jelly (hUCMS), have recently gained growing interest due to their morphological and functional properties. The main purpose of our work was to examine morphology and functional properties of hUCMS retrieved from healthy women as compared to those with obesity, or gestational or type 2 diabetes mellitus, under fair metabolic control. Possible differences between groups could shed light into the potential use of these cells for the cell therapy of a variety of diseases, regardless of the obesity/diabetes status of the donor mothers. Additionally, information on how the maternal disease may affect the cord-derived stem cells, hence possibly newborn children would be important. We have studied obese/diabetic or normal donor post-partum umbilical cord-derived hUCMS, either in basal or during differentiation protocols into several cell phenotypes and the definitive endoderm. Immunomodulatory properties of these cells, in terms of inhibition of activated lymphocyte proliferation, also was examined. According to our preliminary results, there are functional differences, as assessed by cell and molecular assays, in terms of both, differentiation and immunomodulatory potential, between the cells derived from normal as compared to obese/diabetic mothers. The findings seemingly indicate that the uterine environment of obese/diabetic mothers is quite distant from normal, regardless of metabolic control. Hence hUCMS extracted from obese/diabetic mothers do not appear to be suitable for cell therapy clinical protocols but more studies are required.

  12. Elevation of Fasting Ghrelin in Healthy Human Subjects Consuming a High-Salt Diet: A Novel Mechanism of Obesity?

    Science.gov (United States)

    Zhang, Yong; Li, Fenxia; Liu, Fu-Qiang; Chu, Chao; Wang, Yang; Wang, Dan; Guo, Tong-Shuai; Wang, Jun-Kui; Guan, Gong-Chang; Ren, Ke-Yu; Mu, Jian-Jun

    2016-05-26

    Overweight/obesity is a chronic disease that carries an increased risk of hypertension, diabetes mellitus, and premature death. Several epidemiological studies have demonstrated a clear relationship between salt intake and obesity, but the pathophysiologic mechanisms remain unknown. We hypothesized that ghrelin, which regulates appetite, food intake, and fat deposition, becomes elevated when one consumes a high-salt diet, contributing to the progression of obesity. We, therefore, investigated fasting ghrelin concentrations during a high-salt diet. Thirty-eight non-obese and normotensive subjects (aged 25 to 50 years) were selected from a rural community in Northern China. They were sequentially maintained on a normal diet for three days at baseline, a low-salt diet for seven days (3 g/day, NaCl), then a high-salt diet for seven days (18 g/day). The concentration of plasma ghrelin was measured using an immunoenzyme method (ELISA). High-salt intake significantly increased fasting ghrelin levels, which were higher during the high-salt diet (320.7 ± 30.6 pg/mL) than during the low-salt diet (172.9 ± 8.9 pg/mL). The comparison of ghrelin levels between the different salt diets was statistically-significantly different (p high-salt diet elevates fasting ghrelin in healthy human subjects, which may be a novel underlying mechanism of obesity.

  13. Weight loss after gastric bypass surgery in human obesity remodels promoter methylation

    DEFF Research Database (Denmark)

    Barres, Romain; Kirchner, Henriette; Rasmussen, Morten

    2013-01-01

    DNA methylation provides a mechanism by which environmental factors can control insulin sensitivity in obesity. Here, we assessed DNA methylation in skeletal muscle from obese people before and after Roux-en-Y gastric bypass (RYGB). Obesity was associated with altered expression of a subset of ge...... is associated with hypermethylation at CpG shores and exonic regions close to transcription start sites. Our results provide evidence that obesity and RYGB-induced weight loss have a dynamic effect on the epigenome.......DNA methylation provides a mechanism by which environmental factors can control insulin sensitivity in obesity. Here, we assessed DNA methylation in skeletal muscle from obese people before and after Roux-en-Y gastric bypass (RYGB). Obesity was associated with altered expression of a subset...... observed in the normal-weight, healthy subjects. Using bisulfite sequencing, we show that promoter methylation of PGC-1a and PDK4 is altered with obesity and restored to nonobese levels after RYGB-induced weight loss. A genome-wide DNA methylation analysis of skeletal muscle revealed that obesity...

  14. Maternal obesity alters fatty acid oxidation, AMPK activity, and associated DNA methylation in mesenchymal stem cells from human infants.

    Science.gov (United States)

    Boyle, Kristen E; Patinkin, Zachary W; Shapiro, Allison L B; Bader, Carly; Vanderlinden, Lauren; Kechris, Katerina; Janssen, Rachel C; Ford, Rebecca J; Smith, Brennan K; Steinberg, Gregory R; Davidson, Elizabeth J; Yang, Ivana V; Dabelea, Dana; Friedman, Jacob E

    2017-11-01

    Infants born to mothers with obesity have greater adiposity, ectopic fat storage, and are at increased risk for childhood obesity and metabolic disease compared with infants of normal weight mothers, though the cellular mechanisms mediating these effects are unclear. We tested the hypothesis that human, umbilical cord-derived mesenchymal stem cells (MSCs) from infants born to obese (Ob-MSC) versus normal weight (NW-MSC) mothers demonstrate altered fatty acid metabolism consistent with adult obesity. In infant MSCs undergoing myogenesis in vitro, we measured cellular lipid metabolism and AMPK activity, AMPK activation in response to cellular nutrient stress, and MSC DNA methylation and mRNA content of genes related to oxidative metabolism. We found that Ob-MSCs exhibit greater lipid accumulation, lower fatty acid oxidation (FAO), and dysregulation of AMPK activity when undergoing myogenesis in vitro. Further experiments revealed a clear phenotype distinction within the Ob-MSC group where more severe MSC metabolic perturbation corresponded to greater neonatal adiposity and umbilical cord blood insulin levels. Targeted analysis of DNA methylation array revealed Ob-MSC hypermethylation in genes regulating FAO (PRKAG2, ACC2, CPT1A, SDHC) and corresponding lower mRNA content of these genes. Moreover, MSC methylation was positively correlated with infant adiposity. These data suggest that greater infant adiposity is associated with suppressed AMPK activity and reduced lipid oxidation in MSCs from infants born to mothers with obesity and may be an important, early marker of underlying obesity risk. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  15. Human intestinal microbiota composition is associated with local and systemic inflammation in obesity.

    Science.gov (United States)

    Verdam, Froukje J; Fuentes, Susana; de Jonge, Charlotte; Zoetendal, Erwin G; Erbil, Runi; Greve, Jan Willem; Buurman, Wim A; de Vos, Willem M; Rensen, Sander S

    2013-12-01

    Intestinal microbiota have been suggested to contribute to the development of obesity, but the mechanism remains elusive. The relationship between microbiota composition, intestinal permeability, and inflammation in nonobese and obese subjects was investigated. Fecal microbiota composition of 28 subjects (BMI 18.6-60.3 kg m(-2) ) was analyzed by a phylogenetic profiling microarray. Fecal calprotectin and plasma C-reactive protein levels were determined to evaluate intestinal and systemic inflammation. Furthermore, HbA1c , and plasma levels of transaminases and lipids were analyzed. Gastroduodenal, small intestinal, and colonic permeability were assessed by a multisaccharide test. Based on microbiota composition, the study population segregated into two clusters with predominantly obese (15/19) or exclusively nonobese (9/9) subjects. Whereas intestinal permeability did not differ between clusters, the obese cluster showed reduced bacterial diversity, a decreased Bacteroidetes/Firmicutes ratio, and an increased abundance of potential proinflammatory Proteobacteria. Interestingly, fecal calprotectin was only detectable in subjects within the obese microbiota cluster (n = 8/19, P = 0.02). Plasma C-reactive protein was also increased in these subjects (P = 0.0005), and correlated with the Bacteroidetes/Firmicutes ratio (rs = -0.41, P = 0.03). Intestinal microbiota alterations in obese subjects are associated with local and systemic inflammation, suggesting that the obesity-related microbiota composition has a proinflammatory effect. Copyright © 2013 The Obesity Society.

  16. DNA methylation is altered in B and NK lymphocytes in obese and type 2 diabetic human

    DEFF Research Database (Denmark)

    Simar, David; Versteyhe, Soetkin; Donkin, Ida

    2014-01-01

    Objective Obesity is associated with low-grade inflammation and the infiltration of immune cells in insulin-sensitive tissues, leading to metabolic impairment. Epigenetic mechanisms control immune cell lineage determination, function and migration and are implicated in obesity and type 2 diabetes...

  17. "Evaluating Causality of Gut Microbiota in Obesity and Diabetes in Humans"

    NARCIS (Netherlands)

    Meijnikman, Abraham S.; Gerdes, Victor E.; Nieuwdorp, Max; Herrema, Hilde

    2017-01-01

    The pathophysiology of obesity and obesity-related diseases such as type 2 diabetes mellitus (T2DM) is complex and driven by many factors. One of the most recently identified factors in development of these metabolic pathologies is the gut microbiota. The introduction of affordable, high-throughput

  18. Genome wide association study identifies KCNMA1 contributing to human obesity

    DEFF Research Database (Denmark)

    Jiao, Hong; Arner, Peter; Hoffstedt, Johan

    2011-01-01

    Recent genome-wide association (GWA) analyses have identified common single nucleotide polymorphisms (SNPs) that are associated with obesity. However, the reported genetic variation in obesity explains only a minor fraction of the total genetic variation expected to be present in the population...

  19. High-fat Western diet-induced obesity contributes to increased tumor growth in mouse models of human colon cancer.

    Science.gov (United States)

    O'Neill, Ann Marie; Burrington, Christine M; Gillaspie, Erin A; Lynch, Darin T; Horsman, Melissa J; Greene, Michael W

    2016-12-01

    Strong epidemiologic evidence links colon cancer to obesity. The increasing worldwide incidence of colon cancer has been linked to the spread of the Western lifestyle, and in particular consumption of a high-fat Western diet. In this study, our objectives were to establish mouse models to examine the effects of high-fat Western diet-induced obesity on the growth of human colon cancer tumor xenografts, and to examine potential mechanisms driving obesity-linked human colon cancer tumor growth. We hypothesize that mice rendered insulin resistant due to consumption of a high-fat Western diet will show increased and accelerated tumor growth. Homozygous Rag1 tm1Mom mice were fed either a low-fat Western diet or a high-fat Western diet (HFWD), then human colon cancer xenografts were implanted subcutaneously or orthotopically. Tumors were analyzed to detect changes in receptor tyrosine kinase-mediated signaling and expression of inflammatory-associated genes in epididymal white adipose tissue. In both models, mice fed an HFWD weighed more and had increased intra-abdominal fat, and tumor weight was greater compared with in the low-fat Western diet-fed mice. They also displayed significantly higher levels of leptin; however, there was a negative correlation between leptin levels and tumor size. In the orthotopic model, tumors and adipose tissue from the HFWD group displayed significant increases in both c-Jun N-terminal kinase activation and monocyte chemoattractant protein 1 expression, respectively. In conclusion, this study suggests that human colon cancer growth is accelerated in animals that are obese and insulin resistant due to the consumption of an HFWD. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS.

    Science.gov (United States)

    Pan, David Z; Garske, Kristina M; Alvarez, Marcus; Bhagat, Yash V; Boocock, James; Nikkola, Elina; Miao, Zong; Raulerson, Chelsea K; Cantor, Rita M; Civelek, Mete; Glastonbury, Craig A; Small, Kerrin S; Boehnke, Michael; Lusis, Aldons J; Sinsheimer, Janet S; Mohlke, Karen L; Laakso, Markku; Pajukanta, Päivi; Ko, Arthur

    2018-04-17

    Increased adiposity is a hallmark of obesity and overweight, which affect 2.2 billion people world-wide. Understanding the genetic and molecular mechanisms that underlie obesity-related phenotypes can help to improve treatment options and drug development. Here we perform promoter Capture Hi-C in human adipocytes to investigate interactions between gene promoters and distal elements as a transcription-regulating mechanism contributing to these phenotypes. We find that promoter-interacting elements in human adipocytes are enriched for adipose-related transcription factor motifs, such as PPARG and CEBPB, and contribute to heritability of cis-regulated gene expression. We further intersect these data with published genome-wide association studies for BMI and BMI-related metabolic traits to identify the genes that are under genetic cis regulation in human adipocytes via chromosomal interactions. This integrative genomics approach identifies four cis-eQTL-eGene relationships associated with BMI or obesity-related traits, including rs4776984 and MAP2K5, which we further confirm by EMSA, and highlights 38 additional candidate genes.

  1. Association of lipidome remodeling in the adipocyte membrane with acquired obesity in humans.

    Directory of Open Access Journals (Sweden)

    Kirsi H Pietiläinen

    2011-06-01

    Full Text Available Identification of early mechanisms that may lead from obesity towards complications such as metabolic syndrome is of great interest. Here we performed lipidomic analyses of adipose tissue in twin pairs discordant for obesity but still metabolically compensated. In parallel we studied more evolved states of obesity by investigating a separated set of individuals considered to be morbidly obese. Despite lower dietary polyunsaturated fatty acid intake, the obese twin individuals had increased proportions of palmitoleic and arachidonic acids in their adipose tissue, including increased levels of ethanolamine plasmalogens containing arachidonic acid. Information gathered from these experimental groups was used for molecular dynamics simulations of lipid bilayers combined with dependency network analysis of combined clinical, lipidomics, and gene expression data. The simulations suggested that the observed lipid remodeling maintains the biophysical properties of lipid membranes, at the price, however, of increasing their vulnerability to inflammation. Conversely, in morbidly obese subjects, the proportion of plasmalogens containing arachidonic acid in the adipose tissue was markedly decreased. We also show by in vitro Elovl6 knockdown that the lipid network regulating the observed remodeling may be amenable to genetic modulation. Together, our novel approach suggests a physiological mechanism by which adaptation of adipocyte membranes to adipose tissue expansion associates with positive energy balance, potentially leading to higher vulnerability to inflammation in acquired obesity. Further studies will be needed to determine the cause of this effect.

  2. A Postmortem Study of Frontal and Temporal Gyri Thickness and Cell Number in Human Obesity.

    Science.gov (United States)

    Gómez-Apo, Erick; García-Sierra, Adrián; Silva-Pereyra, Juan; Soto-Abraham, Virgilia; Mondragón-Maya, Alejandra; Velasco-Vales, Verónica; Pescatello, Linda S

    2018-01-01

    This study aimed to compare cortex thickness and neuronal cell density in postmortem brain tissue from people with overweight or obesity and normal weight. The cortex thickness and neuron density of eight donors with overweight or obesity (mean = 31.6 kg/m 2 ; SD = 4.35; n = 8; 6 male) and eight donors with normal weight (mean = 21.8 kg/m 2 ; SD = 1.5; n = 8; 5 male) were compared. All participants were Mexican and lived in Mexico City. Randomly selected thickness measures of different cortex areas from the frontal and temporal lobes were analyzed based on high-resolution real-size photographs. A histological analysis of systematic-random fields was used to quantify the number of neurons in postmortem left and right of the first, second, and third gyri of frontal and temporal lobe brain samples. No statistical difference was found in cortical thickness between donors with overweight or obesity and individuals with normal weight. A smaller number of neurons was found among the donors with overweight or obesity than the donors with normal weight at different frontal and temporal areas. A lower density of neurons is associated with overweight or obesity. The morphological basis for structural brain changes in obesity requires further investigation. © 2017 The Obesity Society.

  3. Human serum levels of fetal antigen 1 (FA1/Dlk1) increase with obesity, are negatively associated with insulin sensitivity and modulate inflammation in vitro

    DEFF Research Database (Denmark)

    Chacón, M R; Miranda, M; Jensen, C H

    2008-01-01

    in the context of obesity and insulin sensitivity (S(i)); and n=61 severely obese women before and after bariatric surgery. The response in vitro to FA1 protein on human cell lines of monocytes, preadipocytes and mature adipocytes was studied. MEASUREMENTS: Anthropometrical parameters: body mass index, waist...... levels. In severe obesity, serum levels of FA1 decreased 1.4-fold 6 months after bariatric surgery. In vitro assays with FA1 protein on human monocytes and adipocytes cell lines modified the expression of pro-inflammatory cytokines and adipokines (tumor necrosis factor-alpha (TNFalpha), monocyte...

  4. A Primary Human Trophoblast Model to Study the Effect of Inflammation Associated with Maternal Obesity on Regulation of Autophagy in the Placenta.

    Science.gov (United States)

    Simon, Bailey; Bucher, Matthew; Maloyan, Alina

    2017-09-27

    Maternal obesity is associated with an increased risk of adverse perinatal outcomes that are likely mediated by compromised placental function that can be attributed to, in part, the dysregulation of autophagy. Aberrant changes in the expression of autophagy regulators in the placentas from obese pregnancies may be regulated by inflammatory processes associated with both obesity and pregnancy. Described here is a protocol for sampling of villous tissue and isolation of villous cytotrophoblasts from the term human placenta for primary cell culture. This is followed by a method for simulating the inflammatory milieu in the obese intrauterine environment by treating primary trophoblasts from lean pregnancies with tumor necrosis factor alpha (TNFα), a proinflammatory cytokine that is elevated in obesity and in pregnancy. Through the implementation of the protocol described here, it is found that exposure to exogenous TNFα regulates the expression of Rubicon, a negative regulator of autophagy, in trophoblasts from lean pregnancies with female fetuses. While a variety of biological factors in the obese intrauterine environment maintain the potential to modulate critical pathways in trophoblasts, this ex vivo system is especially useful for determining if expression patterns observed in vivo in human placentas with maternal obesity are a direct result of TNFα signaling. Ultimately, this approach affords the opportunity to parse out the regulatory and molecular implications of inflammation associated with maternal obesity on autophagy and other critical cellular pathways in trophoblasts that have the potential to impact placental function.

  5. Energy expenditure in the etiology of human obesity: spendthrift and thrifty metabolic phenotypes and energy-sensing mechanisms.

    Science.gov (United States)

    Piaggi, P; Vinales, K L; Basolo, A; Santini, F; Krakoff, J

    2018-01-01

    The pathogenesis of human obesity is the result of dysregulation of the reciprocal relationship between food intake and energy expenditure (EE), which influences daily energy balance and ultimately leads to weight gain. According to principles of energy homeostasis, a relatively lower EE in a setting of energy balance may lead to weight gain; however, results from different study groups are contradictory and indicate a complex interaction between EE and food intake which may differentially influence weight change in humans. Recently, studies evaluating the adaptive response of one component to perturbations of the other component of energy balance have revealed both the existence of differing metabolic phenotypes ("spendthrift" and "thrifty") resulting from overeating or underfeeding, as well as energy-sensing mechanisms linking EE to food intake, which might explain the propensity of an individual to weight gain. The purpose of this review is to debate the role that human EE plays on body weight regulation and to discuss the physiologic mechanisms linking EE and food intake. An increased understanding of the complex interplay between human metabolism and food consumption may provide insight into pathophysiologic mechanisms underlying weight gain, which may eventually lead to prevention and better treatment of human obesity.

  6. Elevation of Fasting Ghrelin in Healthy Human Subjects Consuming a High-Salt Diet: A Novel Mechanism of Obesity?

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    2016-05-01

    Full Text Available Overweight/obesity is a chronic disease that carries an increased risk of hypertension, diabetes mellitus, and premature death. Several epidemiological studies have demonstrated a clear relationship between salt intake and obesity, but the pathophysiologic mechanisms remain unknown. We hypothesized that ghrelin, which regulates appetite, food intake, and fat deposition, becomes elevated when one consumes a high-salt diet, contributing to the progression of obesity. We, therefore, investigated fasting ghrelin concentrations during a high-salt diet. Thirty-eight non-obese and normotensive subjects (aged 25 to 50 years were selected from a rural community in Northern China. They were sequentially maintained on a normal diet for three days at baseline, a low-salt diet for seven days (3 g/day, NaCl, then a high-salt diet for seven days (18 g/day. The concentration of plasma ghrelin was measured using an immunoenzyme method (ELISA. High-salt intake significantly increased fasting ghrelin levels, which were higher during the high-salt diet (320.7 ± 30.6 pg/mL than during the low-salt diet (172.9 ± 8.9 pg/mL. The comparison of ghrelin levels between the different salt diets was statistically-significantly different (p < 0.01. A positive correlation between 24-h urinary sodium excretion and fasting ghrelin levels was demonstrated. Our data indicate that a high-salt diet elevates fasting ghrelin in healthy human subjects, which may be a novel underlying mechanism of obesity.

  7. Maternal obesity modulates intracellular lipid turnover in the human term placenta.

    Science.gov (United States)

    Hirschmugl, B; Desoye, G; Catalano, P; Klymiuk, I; Scharnagl, H; Payr, S; Kitzinger, E; Schliefsteiner, C; Lang, U; Wadsack, C; Hauguel-de Mouzon, S

    2017-02-01

    Obesity before pregnancy is associated with impaired metabolic status of the mother and the offspring later in life. These adverse effects have been attributed to epigenetic changes in utero, but little is known about the role of placental metabolism and its contribution to fetal development. We examined the impact of maternal pre-pregnancy obesity on the expression of genes involved in placental lipid metabolism in lean and obese women. Seventy-three lean and obese women with healthy pregnancy were recruited at term elective cesarean delivery. Metabolic parameters were measured on maternal venous blood samples. Expression of 88 genes involved in lipid metabolism was measured in whole placenta tissue. Proteins of genes differently expressed in response to maternal obesity were quantified, correlated with maternal parameters and immunolocalized in placenta sections. Isolated primary trophoblasts were used for in vitro assays. Triglyceride (TG) content was increased in placental tissue of obese (1.10, CI 1.04-1.24 mg g -1 , Pwomen. Among target genes examined, six showed positive correlation (Pobese vs lean women. CGI-58 protein levels correlated positively with maternal insulin levels and pre-pregnancy body mass index (R=0.63, Ptreatment of cultured trophoblast cells. Pre-gravid obesity significantly modifies the expression of placental genes related to transport and storage of neutral lipids. We propose that the upregulation of CGI-58, a master regulator of TG hydrolysis, contributes to the turnover of intracellular lipids in placenta of obese women, and is tightly regulated by metabolic factors of the mother.

  8. Sexual dimorphism in the effect of maternal obesity on antioxidant defense mechanisms in the human placenta.

    Science.gov (United States)

    Evans, LaShauna; Myatt, Leslie

    2017-03-01

    Maternal obesity creates an adverse intrauterine environment, negatively impacts placental respiration, is associated with a higher incidence of pregnancy complications and programs the offspring for disease in adult life in a sexually dimorphic manner. We defined the effect of maternal obesity and fetal sex on pro- and anti-oxidant status in placenta and placental mitochondria. Placental villous tissue was collected at term via c-section prior to labor from four groups of patients based on fetal sex and prepregnancy/1st trimester body mass index: lean - BMI 22.1 ± 0.3 (6 male, 6 female) and obese - BMI 36.3 ± 0.4 (6 male, 6 female). Antioxidant enzyme activity, mitochondrial protein carbonyls, nitrotyrosine residues, total and nitrated superoxide dismutase (SOD) and nitric oxide synthesis were measured. Maternal obesity was associated with decreased SOD and catalase activity, and total antioxidant capacity (TAC), but increased oxidative (protein carbonyls) and nitrative (nitrotyrosine) stress in a sexually dimorphic manner. Placentas of lean women with a male fetus had higher SOD activity and TAC (p < 0.05) than other groups whereas obese women with a male fetus had highest carbonyls and nitrotyrosine (p < 0.05). Glutathione peroxidase and thioredoxin reductase activity increased with obesity, significantly with a male fetus, perhaps as a compensatory response. Maternal obesity affects oxidative stress and antioxidant activity in the placenta in a sexually dimorphic manner. The male fetus of a lean women has the highest antioxidant activity, a protection which is lost with obesity perhaps contributing to the increased incidence of adverse outcomes with a male fetus. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease.

    Science.gov (United States)

    Greenblum, Sharon; Turnbaugh, Peter J; Borenstein, Elhanan

    2012-01-10

    The human microbiome plays a key role in a wide range of host-related processes and has a profound effect on human health. Comparative analyses of the human microbiome have revealed substantial variation in species and gene composition associated with a variety of disease states but may fall short of providing a comprehensive understanding of the impact of this variation on the community and on the host. Here, we introduce a metagenomic systems biology computational framework, integrating metagenomic data with an in silico systems-level analysis of metabolic networks. Focusing on the gut microbiome, we analyze fecal metagenomic data from 124 unrelated individuals, as well as six monozygotic twin pairs and their mothers, and generate community-level metabolic networks of the microbiome. Placing variations in gene abundance in the context of these networks, we identify both gene-level and network-level topological differences associated with obesity and inflammatory bowel disease (IBD). We show that genes associated with either of these host states tend to be located at the periphery of the metabolic network and are enriched for topologically derived metabolic "inputs." These findings may indicate that lean and obese microbiomes differ primarily in their interface with the host and in the way they interact with host metabolism. We further demonstrate that obese microbiomes are less modular, a hallmark of adaptation to low-diversity environments. We additionally link these topological variations to community species composition. The system-level approach presented here lays the foundation for a unique framework for studying the human microbiome, its organization, and its impact on human health.

  10. A new frailty syndrome: central obesity and frailty in older adults with the human immunodeficiency virus.

    Science.gov (United States)

    Shah, Krupa; Hilton, Tiffany N; Myers, Lauren; Pinto, Jonathan F; Luque, Amneris E; Hall, William J

    2012-03-01

    To evaluate the relationships between body composition and physical frailty in community-dwelling older adults with the human immunodeficiency virus (HIV) (HOA). Cross-sectional. Academic hospital-based infectious disease clinic in Rochester, New York. Forty community-dwelling HOA aged 50 and older undergoing antiretroviral therapy who were able to ambulate without assistive devices with a mean age of 58, a mean BMI of 29.0 kg/m(2), mean CD4 count of 569 cells/mL, and a mean duration since HIV diagnosis of 17 years; 28% were female and 57% Caucasian. Subjective and objective measures of functional status were evaluated using the Physical Performance Test (PPT), the graded treadmill test, knee strength, gait speed, balance, and the Functional Status Questionnaire (FSQ). Body composition was evaluated using dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI). Sixty percent (25/40) of the participants met standard criteria for physical frailty. Frail (FR) and nonfrail (NF) participants were comparable in age, sex, CD4 count, and viral load. FR HOA had greater impairments in PPT, peak oxygen uptake, FSQ, walking speed, balance, and muscle quality than NF HOA. FR HOA had a greater body mass index (BMI), fat mass, and truncal fat with lipodystrophy. Moreover, PPT score was inversely related to trunk fat (correlation coefficient (r) = -0.34; P = .04) and ratio of intermuscular fat to total fat (r = -0.60; P = .02) after adjusting for covariates. HOA represent an emerging cohort of older adults who frequently experience frailty at a much younger age than the general older population. Central obesity and fat redistribution are important predictors of frailty in community-dwelling HOA. These findings suggest that physical frailty in HOA may be amenable to lifestyle interventions, especially exercise and diet therapy. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

  11. Diabetogenic activity of native and biosynthetic human growth hormone in obese (ob/ob) mouse.

    Science.gov (United States)

    Kostyo, J L; Gennick, S E; Sauder, S E

    1984-04-01

    It has been repeatedly suggested that diabetogenic activity is not an intrinsic property of native pituitary growth hormone (GH) and that the diabetogenic effects produced by GH preparations are due to low-molecular-weight contaminants or degradation products of the hormone. This possibility was evaluated in this study by assessing the ability of purified native human GH (hGH) and biosynthetic methionyl-hGH to exacerbate fasting hyperglycemia and glucose intolerance in the obese (ob/ob) mouse. Native hGH that had been purified by DEAE-cellulose chromatography (A-type; 1.8 IU/mg) produced fasting hyperglycemia and glucose intolerance in the ob/ob mouse when injected subcutaneously at doses of 50 micrograms/day or greater for 3 days. It had no effect when a single subcutaneous dose of 200 micrograms was administered 24 h previously. To eliminate possible contamination with smaller peptides, the hGH was gel-filtered on a column of Sephacryl S-200 in 6 M guanidine-HCl. When injected subcutaneously into ob/ob mice at a dose of 50 micrograms/day or greater for 3 days, the guanidine-treated hGH produced glucose intolerance. Also biosynthetic methionyl-hGH produced marked fasting hyperglycemia and glucose intolerance when injected subcutaneously at doses of 50 or 100 micrograms/day for 3 days. These results support the conclusion that hGH itself is indeed diabetogenic but that chronic exposure of the organism to the hormone is required for its effects on glucose metabolism to become clearly manifest.

  12. Impaired beta-endorphin response to human corticotropin-releasing hormone in obese children.

    Science.gov (United States)

    Bernasconi, S; Petraglia, F; Iughetti, L; Marcellini, C; Lamborghini, A; Facchinetti, F; Genazzani, A R

    1988-09-01

    In order to evaluate the secretion of beta-endorphin in obese children and adolescents, we measured plasma beta-endorphin, ACTH and cortisol levels before and following administration of CRH (1 microgram/kg). Fourteen normal weight and 22 obese subjects (weight excess ranging from 30 to 98%) were studied. Plasma hormone levels were measured by radioimmunoassay directly in plasma (cortisol, ACTH) and after silicic acid extraction and Sephadex G-75 column chromatography (beta-endorphin). Basal beta-endorphin levels in obese children were significantly higher than in controls (14.7 +/- 1.8 vs 6.0 +/- 0.6 pmol/l; mean +/- SEM). No differences were found in basal ACTH and cortisol levels. CRH administration significantly increased beta-endorphin, ACTH and cortisol levels in normal subjects and ACTH and cortisol levels in obese subjects. Plasma beta-endorphin levels in obese children and adolescents did not show any significant increment. These data confirm the higher than normal beta-endorphin plasma levels in obese subjects in childhood and demonstrate that CRH is unable to increase beta-endorphin levels, suggesting an impairment of the hypothalamo-pituitary control mechanisms or an extra-anterior pituitary source.

  13. Spexin is a novel human peptide that reduces adipocyte uptake of long chain fatty acids and causes weight loss in rodents with diet-induced obesity.

    Science.gov (United States)

    Walewski, José L; Ge, Fengxia; Lobdell, Harrison; Levin, Nancy; Schwartz, Gary J; Vasselli, Joseph R; Pomp, Afons; Dakin, Gregory; Berk, Paul D

    2014-07-01

    Microarray studies identified Ch12:orf39 (Spexin) as the most down-regulated gene in obese human fat. Therefore, we examined its role in obesity pathogenesis. Spexin effects on food intake, meal patterns, body weight, respiratory exchange ratio (RER), and locomotor activity were monitored electronically in C57BL/6J mice or Wistar rats with diet-induced obesity (DIO). Its effects on adipocyte [(3)H]-oleate uptake were determined. In humans, Spexin gene expression was down-regulated 14.9-fold in obese omental and subcutaneous fat. Circulating Spexin changed in parallel, correlating (r = -0.797) with Leptin. In rats, Spexin (35 µg/kg/day SC) reduced caloric intake ∼32% with corresponding weight loss. Meal patterns were unaffected. In mice, Spexin (25 µg/kg/day IP) significantly reduced the RER at night, and increased locomotion. Spexin incubation in vitro significantly inhibited facilitated fatty acid (FA) uptake into DIO mouse adipocytes. Conditioned taste aversion testing (70 µg/kg/day IP) demonstrated no aversive Spexin effects. Spexin gene expression is markedly down-regulated in obese human fat. The peptide produces weight loss in DIO rodents. Its effects on appetite and energy regulation are presumably central; those on adipocyte FA uptake appear direct and peripheral. Spexin is a novel hormone involved in weight regulation, with potential for obesity therapy. Copyright © 2014 The Obesity Society.

  14. Alanine flux in obese and healthy humans as evaluated by 15N- and 2H3-labeled alanines

    International Nuclear Information System (INIS)

    Hoffer, L.J.; Yang, R.D.; Matthews, D.E.; Bistrian, B.R.; Bier, D.M.; Young, V.R.

    1988-01-01

    Estimates of plasma alanine flux as measured in humans using L-[ 15 N]-alanine or L-[3,3,3- 2 H 3 ]alanine were compared by simultaneous intravenous infusion of both tracers. Plasma isotope enrichments were measured by chemical ionization gas chromatography-mass spectrometry. In 16 obese women before and during a hypocaloric diet and in 4 normal men in the postabsorptive and fed states, the fluxes were highly correlated (r2 = 0.93) although plasma alanine flux with the 2 H tracer was two to three times greater than that obtained with [ 15 N]alanine. The fluxes decreased with the hypocaloric diet in obese subjects and increased during the fed state in healthy adults. Thus, although the estimates of alanine flux differed according to the tracer used, both appear to give equivalent information about changes in alanine kinetics induced by the nutritional conditions examined

  15. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans.

    Science.gov (United States)

    Krude, H; Biebermann, H; Luck, W; Horn, R; Brabant, G; Grüters, A

    1998-06-01

    Sequential cleavage of the precursor protein pre-pro-opiomelanocortin (POMC) generates the melanocortin peptides adrenocorticotrophin (ACTH), melanocyte-stimulating hormones (MSH) alpha, beta and gamma as well as the opioid-receptor ligand beta-endorphin. While a few cases of isolated ACTH deficiency have been reported (OMIM 201400), an inherited POMC defect has not been described so far. Recent studies in animal models elucidated a central role of alpha-MSH in the regulation of food intake by activation of the brain melanocortin-4-receptor (MC4-R; refs 3-5) and the linkage of human obesity to chromosome 2 in close proximity to the POMC locus, led to the proposal of an association of POMC with human obesity. The dual role of alpha-MSH in regulating food intake and influencing hair pigmentation predicts that the phenotype associated with a defect in POMC function would include obesity, alteration in pigmentation and ACTH deficiency. The observation of these symptoms in two probands prompted us to search for mutations within their POMC genes. Patient 1 was found to be a compound heterozygote for two mutations in exon 3 (G7013T, C7133delta) which interfere with appropriate synthesis of ACTH and alpha-MSH. Patient 2 was homozygous for a mutation in exon 2 (C3804A) which abolishes POMC translation. These findings represent the first examples of a genetic defect within the POMC gene and define a new monogenic endocrine disorder resulting in early-onset obesity, adrenal insufficiency and red hair pigmentation.

  16. Glucocorticoid mediated regulation of inflammation in human monocytes is associated with depressive mood and obesity.

    Science.gov (United States)

    Cheng, Tiefu; Dimitrov, Stoyan; Pruitt, Christopher; Hong, Suzi

    2016-04-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is observed in various conditions, including depression and obesity, which are also often related. Glucocorticoid (GC) resistance and desensitization of peripheral GC receptors (GRs) are often the case in HPA dysregulation seen in depression, and GC plays a critical role in regulation of inflammation. Given the growing evidence that inflammation is a central feature of some depression cases and obesity, we aimed to investigate the immune-regulatory role of GC-GR in relation to depressive mood and obesity in 35 healthy men and women. Depressive mood and level of obesity were assessed, using Beck Depression Inventory (BDI-Ia) and body mass index (BMI), respectively. We measured plasma cortisol levels via enzyme-linked immunosorbent assay and lipopolysaccharide-stimulated intracellular tumor necrosis factor (TNF) production by monocytes, using flow cytometry. Cortisol sensitivity was determined by the difference in monocytic TNF production between the conditions of 1 and 0 μM cortisol incubation ("cortisol-mediated inflammation regulation, CoMIR"). GR vs. mineralocorticoid receptor (MR) antagonism for CoMIR was examined by using mifepristone and spironolactone. A series of multiple regression analyses were performed to investigate independent contribution of depressive mood vs. obesity after controlling for age, gender, systolic blood pressure (SBP), and plasma cortisol in predicting CoMIR. CoMIR was explained by somatic subcomponents of depressive mood (BDI-S: β=-0.499, p=0.001), or BMI (β=-0.466, pcortisol dose (1 μM). There was initial indication that greater obesity and somatic depressive symptoms were associated with smaller efficacy of the blockers, which warrants further investigation. Our findings, although in a preclinical sample, signify the shared pathophysiology of immune dysregulation in depression and obesity and warrant further mechanistic investigation. Published by Elsevier Ltd.

  17. Obesity-related DNA methylation at imprinted genes in human sperm: Results from the TIEGER study.

    Science.gov (United States)

    Soubry, Adelheid; Guo, Lisa; Huang, Zhiqing; Hoyo, Cathrine; Romanus, Stephanie; Price, Thomas; Murphy, Susan K

    2016-01-01

    Epigenetic reprogramming in mammalian gametes resets methylation marks that regulate monoallelic expression of imprinted genes. In males, this involves erasure of the maternal methylation marks and establishment of paternal-specific methylation to appropriately guide normal development. The degree to which exogenous factors influence the fidelity of methylation reprogramming is unknown. We previously found an association between paternal obesity and altered DNA methylation in umbilical cord blood, suggesting that the father's endocrine, nutritional, or lifestyle status could potentiate intergenerational heritable epigenetic abnormalities. In these analyses, we examine the relationship between male overweight/obesity and DNA methylation status of imprinted gene regulatory regions in the gametes. Linear regression models were used to compare sperm DNA methylation percentages, quantified by bisulfite pyrosequencing, at 12 differentially methylated regions (DMRs) from 23 overweight/obese and 44 normal weight men. Our study population included 69 volunteers from The Influence of the Environment on Gametic Epigenetic Reprogramming (TIEGER) study, based in NC, USA. After adjusting for age and fertility patient status, semen from overweight or obese men had significantly lower methylation percentages at the MEG3 (β = -1.99; SE = 0.84; p = 0.02), NDN (β = -1.10; SE = 0.47; p = 0.02), SNRPN (β = -0.65; SE = 0.27; p = 0.02), and SGCE/PEG10 (β = -2.5; SE = 1.01; p = 0.01) DMRs. Our data further suggest a slight increase in DNA methylation at the MEG3-IG DMR (β = +1.22; SE = 0.59; p = 0.04) and H19 DMR (β = +1.37; SE = 0.62; p = 0.03) in sperm of overweight/obese men. Our data support that male overweight/obesity status is traceable in the sperm epigenome. Further research is needed to understand the effect of such changes and the point of origin of DNA methylation differences between lean and

  18. Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade.

    Science.gov (United States)

    Pedersen, Morten Høgild; Svart, Mads Vandsted; Lebeck, Janne; Bidlingmaier, Martin; Stødkilde-Jørgensen, Hans; Pedersen, Steen Bønløkke; Møller, Niels; Jessen, Niels; Jørgensen, Jens O L

    2017-04-01

    Insulin resistance and metabolic inflexibility are features of obesity and are amplified by fasting. Growth hormone (GH) secretion increases during fasting and GH causes insulin resistance. To study the metabolic effects of GH blockade during fasting in obese subjects. Nine obese males were studied thrice in a randomized design: (1) after an overnight fast (control), (2) after 72 hour fasting (fasting), and (3) after 72 hour fasting with GH blockade (pegvisomant) [fasting plus GH antagonist (GHA)]. Each study day consisted of a 4-hour basal period followed by a 2-hour hyperinsulinemic, euglycemic clamp combined with indirect calorimetry, assessment of glucose and palmitate turnover, and muscle and fat biopsies. GH levels increased with fasting (P fasting-induced reduction of serum insulin-like growth factor I was enhanced by GHA (P Fasting increased lipolysis and lipid oxidation independent of GHA, but fasting plus GHA caused a more pronounced suppression of lipid intermediates in response to hyperinsulinemic, euglycemic clamp. Fasting-induced insulin resistance was abrogated by GHA (P Fasting plus GHA also caused elevated glycerol levels and reduced levels of counterregulatory hormones. Fasting significantly reduced the expression of antilipolytic signals in adipose tissue independent of GHA. Suppression of GH activity during fasting in obese subjects reverses insulin resistance and amplifies insulin-stimulated suppression of lipid intermediates, indicating that GH is an important regulator of substrate metabolism, insulin sensitivity, and metabolic flexibility also in obese subjects. Copyright © 2017 by the Endocrine Society

  19. Hormonal and Dietary Characteristics in Obese Human Subjects with and without Food Addiction

    Directory of Open Access Journals (Sweden)

    Pardis Pedram

    2014-12-01

    Full Text Available The concept of food addiction (FA is a potentially important contributing factor to the development of obesity in the general population; however, little is known about the hormonal and dietary differences between obesity with and without FA. Therefore, the aim of our study was to explore potential biomarkers, including various hormones and neuropeptides, which regulate appetite and metabolism, and dietary components that could potentially differentiate obesity with and without FA. Of the 737 adults recruited from the general Newfoundland population, 58 food-addicted and non-food-addicted overweight/obese individuals (FAO, NFO matched for age, sex, BMI and physical activity were selected. A total of 34 neuropeptides, gut hormones, pituitary polypeptide hormones and adipokines were measured in fasting serum. We found that the FAO group had lower levels of TSH, TNF-α and amylin, but higher levels of prolactin, as compared to NFO group. The total calorie intake (per kg body weight, the dietary intake of fat (per g/kg body weight, per BMI and per percentage of trunk fat and the percent calorie intake from fat and carbohydrates (g/kg was higher in the FAO group compared to the NFO group. The FAO subjects consumed more sugar, minerals (including sodium, potassium, calcium and selenium, fat and its components (such as saturated, monounsaturated and trans fat, omega 3 and 6, vitamin D and gamma-tocopherol compared to the NFO group. To our knowledge, this is the first study indicating possible differences in hormonal levels and micro-nutrient intakes between obese individuals classified with and without food addiction. The findings provide insights into the mechanisms by which FA could contribute to obesity.

  20. Effects of Weight Loss and Exercise on Apelin Serum Concentrations and Adipose Tissue Expression in Human Obesity

    Directory of Open Access Journals (Sweden)

    Joanna Krist

    2013-02-01

    Full Text Available Objective: Apelin is an adipokine which plays a role in the regulation of glucose homeostasis and may contribute to the link between increased adipose tissue mass and obesity related metabolic diseases. Here we investigate the role of omental and subcutaneous (SC adipose tissue apelin and its receptor APJ mRNA expression in human obesity and test the hypothesis that changes in circulating apelin are associated with reduced fat mass in three weight loss intervention studies. Methods: Apelin serum concentration was measured in 740 individuals in a cross-sectional (n = 629 study including a subgroup (n = 161 for which omental and SC apelin mRNA expression has been analyzed and in three interventions: 12 weeks exercise (n = 60, 6 months calorie-restricted diet (n = 19, 12 months after bariatric surgery (n = 32. Results: Apelin mRNA is significantly higher expressed in adipose tissue of patients with type 2 diabetes and correlates with circulating apelin, BMI, body fat, C-reactive protein, and insulin sensitivity. Obesity surgery-induced weight loss causes a significant reduction in omental and SC apelin expression. All interventions led to significantly reduced apelin serum concentrations which significantly correlate with improved insulin sensitivity, independently of changes in BMI. Conclusions: Reduced apelin expression and serum concentration may contribute to improved insulin sensitivity beyond significant weight loss.

  1. Effects of weight loss and exercise on apelin serum concentrations and adipose tissue expression in human obesity.

    Science.gov (United States)

    Krist, Joanna; Wieder, Katharina; Klöting, Nora; Oberbach, Andreas; Kralisch, Susan; Wiesner, Tobias; Schön, Michael R; Gärtner, Daniel; Dietrich, Arne; Shang, Edward; Lohmann, Tobias; Dreßler, Miriam; Fasshauer, Mathias; Stumvoll, Michael; Blüher, Matthias

    2013-01-01

    Apelin is an adipokine which plays a role in the regulation of glucose homeostasis and may contribute to the link between increased adipose tissue mass and obesity related metabolic diseases. Here we investigate the role of omental and subcutaneous (SC) adipose tissue apelin and its receptor APJ mRNA expression in human obesity and test the hypothesis that changes in circulating apelin are associated with reduced fat mass in three weight loss intervention studies. Apelin serum concentration was measured in 740 individuals in a cross-sectional (n = 629) study including a subgroup (n = 161) for which omental and SC apelin mRNA expression has been analyzed and in three interventions: 12 weeks exercise (n = 60), 6 months calorie-restricted diet (n = 19), 12 months after bariatric surgery (n = 32). Apelin mRNA is significantly higher expressed in adipose tissue of patients with type 2 diabetes and correlates with circulating apelin, BMI, body fat, C-reactive protein, and insulin sensitivity. Obesity surgery-induced weight loss causes a significant reduction in omental and SC apelin expression. All interventions led to significantly reduced apelin serum concentrations which significantly correlate with improved insulin sensitivity, independently of changes in BMI. Reduced apelin expression and serum concentration may contribute to improved insulin sensitivity beyond significant weight loss.

  2. Effects of living at two ambient temperatures on 24-h blood pressure and neuroendocrine function among obese and non-obese humans: a pilot study

    Science.gov (United States)

    Kanikowska, Dominika; Sato, Maki; Iwase, Satoshi; Shimizu, Yuuki; Nishimura, Naoki; Inukai, Yoko; Sugenoya, Junichi

    2013-05-01

    The effects of environmental temperature on blood pressure and hormones in obese subjects in Japan were compared in two seasons: summer vs winter. Five obese (BMI, 32 ± 5 kg/m2) and five non-obese (BMI, 23 ±3 kg/m2) men participated in this experiment at latitude 35°10' N and longitude 136°57.9' E. The average environmental temperature was 29 ± 1 °C in summer and 3 ± 1 °C in winter. Blood samples were analyzed for leptin, ghrelin, catecholamines, thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), total cholesterol, triglycerides, insulin and glucose. Blood pressure was measured over the course of 24 h in summer and winter. A Japanese version of the Profile of Mood States (POMS) questionnaire was also administered each season. Systolic and diastolic blood pressures in obese men were significantly higher in winter (lower environmental temperatures) than in summer (higher environmental temperatures). Noradrenaline and dopamine concentrations were also significantly higher at lower environmental temperatures in obese subjects, but ghrelin, TSH, fT3, fT4, insulin and glucose were not significantly different in summer and winter between obese and non-obese subjects. Leptin, total cholesterol and triglyceride concentrations were significantly higher in winter in obese than non-obese men. Results from the POMS questionnaire showed a significant rise in Confusion at lower environmental temperatures (winter) in obese subjects. In this pilot study, increased blood pressure may have been due to increased secretion of noradrenaline in obese men in winter, and the results suggest that blood pressure control in obese men is particularly important in winter.

  3. Sexual dimorphism in hepatic, adipose tissue and peripheral tissue insulin sensitivity in obese humans

    Directory of Open Access Journals (Sweden)

    Kasper W. ter Horst

    2015-11-01

    Full Text Available Glucose and lipid metabolism differ between men and women, and women tend to have better whole-body or muscle insulin sensitivity. This may be explained, in part, by differences in sex hormones and adipose tissue distribution. Few studies have investigated gender differences in hepatic, adipose tissue and whole-body insulin sensitivity between severely obese men and women. In this study, we aimed to determine the differences in glucose metabolism between severely obese men and women using tissue-specific measurements of insulin sensitivity. Insulin sensitivity was compared between age and body mass index (BMI-matched obese men and women by a two-step euglycemic hyperinsulinemic clamp with infusion of [6,6-2H2]glucose. Basal endogenous glucose production and insulin sensitivity of the liver, adipose tissue and peripheral tissues were assessed. Liver fat content was assessed by proton magnetic resonance spectroscopy in a subset of included subjects. We included 46 obese men and women (age, 48±2 vs 46±2 years, p=0.591; BMI, 41±1 vs 41±1 kg/m2, p=0.832. There was no difference in basal endogenous glucose production (14.4±1.0 vs 15.3±0.5 µmol•kg fat-free mass-1•min-1, p=0.410, adipose tissue insulin sensitivity (insulin-mediated suppression of free fatty acids, 71.6±3.6 vs 76.1±2.6%, p=0.314 or peripheral insulin sensitivity (insulin-stimulated rate of disappearance of glucose, 26.2±2.1 vs 22.7±1.7 µmol•kg-1•min-1, p=0.211. Obese men were characterized by lower hepatic insulin sensitivity (insulin-mediated suppression of endogenous glucose production, 61.7±4.1 vs 72.8±2.5% in men vs women, resp., p=0.028. Finally, these observations could not be explained by differences in liver fat content (men vs women, 16.5±3.1 vs 16.0±2.5%, p=0.913, n=27.We conclude that obese men have lower hepatic, but comparable adipose tissue and peripheral tissue, insulin sensitivity compared to similarly obese women. Hepatic insulin resistance may

  4. Maternal Obesity and Cardiac Development in the Offspring: Study in Human Neonates and Minipigs.

    Science.gov (United States)

    Guzzardi, Maria Angela; Liistro, Tiziana; Gargani, Luna; Ait Ali, Lamia; D'Angelo, Gennaro; Rocchiccioli, Silvia; La Rosa, Federica; Kemeny, Alessandra; Sanguinetti, Elena; Ucciferri, Nadia; De Simone, Mariarosaria; Bartoli, Antonietta; Festa, Pierluigi; Salvadori, Piero A; Burchielli, Silvia; Sicari, Rosa; Iozzo, Patricia

    2017-11-10

    The aim of this study was to investigate the consequences of maternal overweight on cardiac development in offspring in infants (short term) and minipigs (short and longer term). The epidemic of overweight involves pregnant women. The uterine environment affects organ development, modulating disease susceptibility. Offspring of obese mothers have higher rates of cardiovascular events and mortality. Echocardiography was performed in infants born to lean and overweight mothers at birth and at 3, 6, and 12 months of age. In minipigs born to mothers fed a high-fat diet or a normal diet, cardiac development (echocardiography, histology), glucose metabolism and perfusion (positron emission tomography), triglyceride and glycogen content, and myocardial enzymes regulating metabolism (mass spectrometry) were determined from birth to adulthood. In neonates, maternal overweight, especially in the last trimester, predicted a thicker left ventricular posterior wall at birth (4.1 ± 0.3 vs. 3.3 ± 0.2 mm; p < 0.05) and larger end-diastolic and stroke volumes at 1 year. Minipigs born to mothers fed a high-fat diet showed greater left ventricular mass (p = 0.0001), chambers (+100%; p < 0.001), stroke volume (+75%; p = 0.001), cardiomyocyte nuclei (+28%; p = 0.02), glucose uptake, and glycogen accumulation at birth (+100%; p < 0.005), with lower levels of oxidative enzymes, compared with those born to mothers fed a normal diet. Subsequently, they developed myocardial insulin resistance and glycogen depletion. Late adulthood showed elevated heart rate (111 ± 5 vs. 84 ± 8 beats/min; p < 0.05) and ejection fraction and deficient fatty acid oxidative enzymes. Neonatal changes in cardiac morphology were explained by late-trimester maternal body mass index; myocardial glucose overexposure seen in minipigs can justify early human findings. Longer term effects in minipigs consisted of myocardial insulin resistance, enzymatic alterations, and hyperdynamic systolic function

  5. Spexin is a Novel Human Peptide that Reduces Adipocyte Uptake of Long Chain Fatty Acids and Causes Weight Loss in Rodents with Diet-induced Obesity*

    Science.gov (United States)

    Walewski, José L.; Ge, Fengxia; Lobdell, Harrison; Levin, Nancy; Schwartz, Gary J.; Vasselli, Joseph; Pomp, Afons; Dakin, Gregory; Berk, Paul D.

    2014-01-01

    Objective Microarray studies identified Ch12:orf39 (Spexin) as the most dysregulated gene in obese human fat. Therefore we examined its role in obesity pathogenesis. Design and Methods Spexin effects on food intake, meal patterns, body weight, Respiratory Exchange Ratio (RER), and locomotor activity were monitored electronically in C57BL/6J mice or Wistar rats with dietary-induced obesity (DIO). Its effects on adipocyte [3H]-oleate uptake were determined. Results In humans, Spexin gene expression was down-regulated 14.9-fold in obese omental and subcutaneous fat. Circulating Spexin changed in parallel, correlating (r = −0.797) with Leptin. In rats, Spexin (35 μg/kg/day s.c) reduced caloric intake ~32% with corresponding weight loss. Meal patterns were unaffected. In mice, Spexin (25 μg/kg/day i.p.) significantly reduced the RER at night, and increased locomotion. Spexin incubation in vitro significantly inhibited facilitated fatty acid (FA) uptake into DIO mouse adipocytes. Conditioned taste aversion testing (70μg/kg/day i.p.) demonstrated no aversive Spexin effects. Conclusions Spexin gene expression is markedly down-regulated in obese human fat. The peptide produces weight loss in DIO rodents. Its effects on appetite and energy regulation are presumably central; those on adipocyte FA uptake appear direct and peripheral. Spexin is a novel hormone involved in weight regulation, with potential for obesity therapy. PMID:24550067

  6. Hibiscus sabdariffa extract inhibits obesity and fat accumulation, and improves liver steatosis in humans.

    Science.gov (United States)

    Chang, Hong-Chou; Peng, Chiung-Huei; Yeh, Da-Ming; Kao, Erl-Shyh; Wang, Chau-Jong

    2014-04-01

    Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease. Our previous report suggested that Hibiscus sabdariffa extracts (HSE) had a metabolic-regulating and liver-protecting potential. In this study, we performed a clinical trial to further confirm the effect of HSE. Subjects with a BMI ≧ 27 and aged 18-65, were randomly divided into control (n = 17) and HSE-treated (n = 19) groups, respectively, for 12 weeks. Our data showed that consumption of HSE reduced body weight, BMI, body fat and the waist-to-hip ratio. Serum free fatty acid (FFA) was lowered by HSE. Anatomic changes revealed that HSE improved the illness of liver steatosis. Ingestion of HSE was well tolerated and there was no adverse effect during the trial. No alteration was found for serum α-amylase and lipase. The clinical effect should mainly be attributed to the polyphenols of HSE, since composition analysis showed that branched chain-amino acids, which is associated with obesity, is not obviously high. In conclusion, consumption of HSE reduced obesity, abdominal fat, serum FFA and improved liver steatosis. HSE could act as an adjuvant for preventing obesity and non-alcoholic fatty liver.

  7. Plasma Amino Acids Stimulate Uncoupled Respiration of Muscle Subsarcolemmal Mitochondria in Lean but Not Obese Humans.

    Science.gov (United States)

    Kras, Katon A; Hoffman, Nyssa; Roust, Lori R; Patel, Shivam H; Carroll, Chad C; Katsanos, Christos S

    2017-12-01

    Obesity is associated with mitochondrial dysfunction in skeletal muscle. Increasing the plasma amino acid (AA) concentrations stimulates mitochondrial adenosine triphosphate (ATP) production in lean individuals. To determine whether acute elevation in plasma AAs enhances muscle mitochondrial respiration and ATP production in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in obese adults. Assessment of SS and IMF mitochondrial function during saline (i.e., control) and AA infusions. Eligible participants were healthy lean (body mass index, 30 kg/m2; age 35 ± 3 years; n = 11) subjects. Single trial of saline infusion followed by AA infusion. SS and IMF mitochondria were isolated from muscle biopsies collected at the end of the saline and AA infusions. Mitochondrial respiration and ATP production. AA infusion increased adenosine 5'-diphosphate (ADP)-stimulated respiration and ATP production rates of SS mitochondria in the lean (P lean subjects only (P lean or obese subjects (P > 0.05). Increasing the plasma AA concentrations enhances the capacity for respiration and ATP production of muscle SS, but not IMF, mitochondria in lean individuals, in parallel with increases in uncoupled respiration. However, neither of these parameters increases in muscle SS or IMF mitochondria in obese individuals. Copyright © 2017 Endocrine Society

  8. Maternal obesity programs senescence signaling and glucose metabolism in osteo-progenitors from rat and human

    Science.gov (United States)

    Nutritional status during intrauterine and early postnatal life impacts the risk of chronic diseases, presumably via epigenetic mechanisms. However, evidence on the impact of gestational events on regulation of embryonic bone cell fate is sparse. We investigated the effects of maternal obesity on fe...

  9. Influence of exogenous human growth hormone on the metabolism of fasting obese patients

    NARCIS (Netherlands)

    Schwarz, F.; Kinderen, P.J. der; Riet, H.G. van; Thijssen, J.H.H.; Wayjen, R.G.A.

    Three obese female patients were investigated during three courses of starvation. In two of them these periods lasted 12 days; in one 6 days. During the second starvation period HGH was administered on alternate days in a dosage of 10 mg. Plasma values of FFA, hydroxybutyric acid, insulin,

  10. Obesity and the Endometrium: Adipocyte-Secreted Proinflammatory TNFα Cytokine Enhances the Proliferation of Human Endometrial Glandular Cells

    Directory of Open Access Journals (Sweden)

    Sangeeta Nair

    2013-01-01

    Full Text Available Obesity, a state of chronic inflammation, is associated with poor fertility and low implantation rates and is a well-documented risk factor for endometrial cancer. Adipokines, such as tumor necrosis factor alpha, play an important role in initiation of endometrial cancer. The aim of this study is to evaluate in vitro effects of human adipocyte cells (SW872 on growth of endometrial glandular epithelial cells (EGE. Methods. We measured cell proliferation and expression of cell-growth proteins—proliferating cell nuclear antigen, cyclin D1, cyclin-dependent kinase-1, and apoptotic markers (BCL-2 and BAK in human EGE cells cocultured with SW872 cells. EGE cells were also evaluated in SW872-conditioned media neutralized with anti-TNFα antibody. Results. A significant increase in EGE cell proliferation was observed in both SW872-conditioned media and in coculture (P<0.05. We observed an upregulation of proliferation markers PCNA, cyclin D1, CDK-1, and BCL-2 and decrease in BAK (P<0.05. Neutralization of SW872-conditioned media using anti-TNFα antibodies reversed EGE cell proliferation as indicated by BCL-2 expression. Conclusions. Adipocytes have potent proliferative paracrine effect on EGE cells which may be, in part, mediated via TNFα. Further understanding of the role of obesity in endometrial carcinogenesis should lead to better preventative and therapeutic strategies.

  11. Association of Lipidome Remodeling in the Adipocyte Membrane with Acquired Obesity in Humans

    DEFF Research Database (Denmark)

    Pietilainen, K. H.; Rog, T.; Seppanen-Laakso, T.

    2011-01-01

    Identification of early mechanisms that may lead from obesity towards complications such as metabolic syndrome is of great interest. Here we performed lipidomic analyses of adipose tissue in twin pairs discordant for obesity but still metabolically compensated. In parallel we studied more evolved...... of ethanolamine plasmalogens containing arachidonic acid. Information gathered from these experimental groups was used for molecular dynamics simulations of lipid bilayers combined with dependency network analysis of combined clinical, lipidomics, and gene expression data. The simulations suggested...... also show by in vitro Elovl6 knockdown that the lipid network regulating the observed remodeling may be amenable to genetic modulation. Together, our novel approach suggests a physiological mechanism by which adaptation of adipocyte membranes to adipose tissue expansion associates with positive energy...

  12. Type 2 diabetes and obesity induce similar transcriptional reprogramming in human myocytes

    DEFF Research Database (Denmark)

    Väremo, Leif; Henriksen, Tora Ida; Scheele, Camilla

    2017-01-01

    in sphingolipid metabolism was transcriptionally regulated. CONCLUSIONS: Our findings identify inherent characteristics in myocytes, as a memory of the in vivo phenotype, without the influence from a diabetic or obese extracellular environment, highlighting their importance in the development of T2D.......BACKGROUND: Skeletal muscle is one of the primary tissues involved in the development of type 2 diabetes (T2D). The close association between obesity and T2D makes it difficult to isolate specific effects attributed to the disease alone. Therefore, here we set out to identify and characterize...... on genome-wide transcription. This setup enabled us to identify intrinsic properties, originating from muscle precursor cells and retained in the corresponding myocytes. Bioinformatic and statistical methods, including differential expression analysis, gene-set analysis, and metabolic network analysis, were...

  13. Efficacy of Slim339 in reducing body weight of overweight and obese human subjects.

    Science.gov (United States)

    Toromanyan, Edward; Aslanyan, Gayane; Amroyan, Elmira; Gabrielyan, Emil; Panossian, Alexander

    2007-12-01

    A double-blind, randomized, parallel-group, placebo-controlled study has been carried out in order to evaluate the effect of orally self-administered Slim339, a proprietary fixed combination of Garcinia cambogia extract with calcium pantothenate (standardized for the content of hydroxycitric acid and pantothenic acid) and extracts of Matricaria chamomilla, Rosa damascena, Lavandula officinalis and Cananga odorata, on body weight in overweight and obese volunteers. During a 60-day treatment period, the average reduction in body weight for the group receiving Slim339 (n = 30) was 4.67% compared with 0.63% for the placebo group (n = 28) (p or=3 kg were recorded for 23 subjects in the treatment group and only one in the placebo group. It is concluded that Slim339 represents a potential therapy for obesity. Copyright (c) 2007 John Wiley & Sons, Ltd.

  14. Obesity-related known and candidate SNP markers can significantly change affinity of TATA-binding protein for human gene promoters.

    Science.gov (United States)

    Arkova, Olga V; Ponomarenko, Mikhail P; Rasskazov, Dmitry A; Drachkova, Irina A; Arshinova, Tatjana V; Ponomarenko, Petr M; Savinkova, Ludmila K; Kolchanov, Nikolay A

    2015-01-01

    Obesity affects quality of life and life expectancy and is associated with cardiovascular disorders, cancer, diabetes, reproductive disorders in women, prostate diseases in men, and congenital anomalies in children. The use of single nucleotide polymorphism (SNP) markers of diseases and drug responses (i.e., significant differences of personal genomes of patients from the reference human genome) can help physicians to improve treatment. Clinical research can validate SNP markers via genotyping of patients and demonstration that SNP alleles are significantly more frequent in patients than in healthy people. The search for biomedical SNP markers of interest can be accelerated by computer-based analysis of hundreds of millions of SNPs in the 1000 Genomes project because of selection of the most meaningful candidate SNP markers and elimination of neutral SNPs. We cross-validated the output of two computer-based methods: DNA sequence analysis using Web service SNP_TATA_Comparator and keyword search for articles on comorbidities of obesity. Near the sites binding to TATA-binding protein (TBP) in human gene promoters, we found 22 obesity-related candidate SNP markers, including rs10895068 (male breast cancer in obesity); rs35036378 (reduced risk of obesity after ovariectomy); rs201739205 (reduced risk of obesity-related cancers due to weight loss by diet/exercise in obese postmenopausal women); rs183433761 (obesity resistance during a high-fat diet); rs367732974 and rs549591993 (both: cardiovascular complications in obese patients with type 2 diabetes mellitus); rs200487063 and rs34104384 (both: obesity-caused hypertension); rs35518301, rs72661131, and rs562962093 (all: obesity); and rs397509430, rs33980857, rs34598529, rs33931746, rs33981098, rs34500389, rs63750953, rs281864525, rs35518301, and rs34166473 (all: chronic inflammation in comorbidities of obesity). Using an electrophoretic mobility shift assay under nonequilibrium conditions, we empirically validated the

  15. Impact of Metabolic Hormones Secreted in Human Breast Milk on Nutritional Programming in Childhood Obesity.

    Science.gov (United States)

    Badillo-Suárez, Pilar Amellali; Rodríguez-Cruz, Maricela; Nieves-Morales, Xóchitl

    2017-09-01

    Obesity is the most common metabolic disease whose prevalence is increasing worldwide. This condition is considered a serious public health problem due to associated comorbidities such as diabetes mellitus and hypertension. Perinatal morbidity related to obesity does not end with birth; this continues affecting the mother/infant binomial and could negatively impact on metabolism during early infant nutrition. Nutrition in early stages of growth may be essential in the development of obesity in adulthood, supporting the concept of "nutritional programming". For this reason, breastfeeding may play an important role in this programming. Breast milk is the most recommended feeding for the newborn due to the provided benefits such as protection against obesity and diabetes. Health benefits are based on milk components such as bioactive molecules, specifically hormones involved in the regulation of food intake. Identification of these molecules has increased in recent years but its action has not been fully clarified. Hormones such as leptin, insulin, ghrelin, adiponectin, resistin, obestatin and insulin-like growth factor-1 copeptin, apelin, and nesfatin, among others, have been identified in the milk of normal-weight women and may influence the energy balance because they can activate orexigenic or anorexigenic pathways depending on energy requirements and body stores. It is important to emphasize that, although the number of biomolecules identified in milk involved in regulating food intake has increased considerably, there is a lack of studies aimed at elucidating the effect these hormones may have on metabolism and development of the newborn. Therefore, we present a state-of-the-art review regarding bioactive compounds such as hormones secreted in breast milk and their possible impact on nutritional programming in the infant, analyzing their functions in appetite regulation.

  16. Pro-inflammatory wnt5a and anti-inflammatory sFRP5 are differentially regulated by nutritional factors in obese human subjects.

    Directory of Open Access Journals (Sweden)

    Dominik M Schulte

    Full Text Available Obesity is associated with macrophage infiltration of adipose tissue. These inflammatory cells affect adipocytes not only by classical cytokines but also by the secreted glycopeptide wnt5a. Healthy adipocytes are able to release the wnt5a inhibitor sFRP5. This protective effect, however, was found to be diminished in obesity. The aim of the present study was to examine (1 whether obese human subjects exhibit increased serum concentrations of wnt5a and (2 whether wnt5a and/or sFRP5 serum concentrations in obese subjects can be influenced by caloric restriction.23 obese human subjects (BMI 44.1 ± 1.1 kg/m(2 and 12 age- and sex-matched lean controls (BMI 22.3 ± 0.4 kg/m(2 were included in the study. Obese subjects were treated with a very low-calorie diet (approximately 800 kcal/d for 12 weeks. Body composition was assessed by impedance analysis, insulin sensitivity was estimated by HOMA-IR and the leptin-to-adiponectin ratio and wnt5a and sFRP5 serum concentrations were measured by ELISA. sFRP5 expression in human adipose tissue biopsies was further determined on protein level by immunohistology.Pro-inflammatory wnt5a was not measurable in any serum sample of lean control subjects. In patients with obesity, however, wnt5a became significantly detectable consistent with low grade inflammation in such subjects. Caloric restriction resulted in a weight loss from 131.9 ± 4.0 to 112.3 ± 3.2 kg in the obese patients group. This was accompanied by a significant decrease of HOMA-IR and leptin-to-adiponectin ratio, indicating improved insulin sensitivity. Interestingly, these metabolic improvements were associated with a significant increase in serum concentrations of the anti-inflammatory factor and wnt5a-inhibitor sFRP5.Obesity is associated with elevated serum levels of pro-inflammatory wnt5a in humans. Furthermore, caloric restriction beneficially affects serum concentrations of anti-inflammatory sFRP5 in such subjects. These findings suggest a

  17. Farnesol Has an Anti-obesity Effect in High-Fat Diet-Induced Obese Mice and Induces the Development of Beige Adipocytes in Human Adipose Tissue Derived-Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Hye-Lin Kim

    2017-09-01

    Full Text Available Brown adipocytes dissipate energy as heat and hence have an important therapeutic capacity for obesity. Development of brown-like adipocytes (also called beige is also another attractive target for obesity treatment. Here, we investigated the effect of farnesol, an isoprenoid, on adipogenesis in adipocytes and on the browning of white adipose tissue (WAT as well as on the weight gain of high-fat diet (HFD-induced obese mice. Farnesol inhibited adipogenesis and the related key regulators including peroxisome proliferator-activated receptor γ (PPARγ and CCAAT/enhancer binding protein α through the up-regulation of AMP-activated protein kinase in 3T3-L1 murine adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs. Farnesol markedly increased the expression of uncoupling protein 1 and PPARγ coactivator 1 α in differentiated hAMSCs. In addition, farnesol limited the weight gain in HFD obese mice and induced the development of beige adipocytes in both inguinal and epididymal WAT. These results suggest that farnesol could be a potential therapeutic agent for obesity treatment.

  18. Obesity Prevention and Screening.

    Science.gov (United States)

    Mackey, Eleanor R; Olson, Alexandra; DiFazio, Marc; Cassidy, Omni

    2016-03-01

    Obesity is widespread, associated with several physical and psychosocial comorbidities, and is difficult to treat. Prevention of obesity across the lifespan is critical to improving the health of individuals and society. Screening and prevention efforts in primary care are an important step in addressing the obesity epidemic. Each period of human development is associated with unique risks, challenges, and opportunities for prevention and intervention. Screening tools for overweight/obesity, although imperfect, are quick and easy to administer. Screening should be conducted at every primary care visit and tracked longitudinally. Screening tools and cutoffs for overweight and obesity vary by age group. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. B Lymphocyte Stimulator (BLyS is expressed in human adipocytes in vivo and is related to obesity but not to insulin resistance.

    Directory of Open Access Journals (Sweden)

    Nike Müller

    Full Text Available Inflammation and metabolism have been shown to be evolutionary linked and increasing evidence exists that pro-inflammatory factors are involved in the pathogenesis of obesity and type 2 diabetes. Until now, most data suggest that within adipose tissue these factors are secreted by cells of the innate immune system, e. g. macrophages. In the present study we demonstrate that B lymphocyte stimulator (BLyS is increased in human obesity. In contrast to several pro-inflammatory factors, we found the source of BLyS in human adipose tissue to be the adipocytes rather than immune cells. In grade 3 obese human subjects, expression of BLyS in vivo in adipose tissue is significantly increased (p<0.001. Furthermore, BLyS serum levels are elevated in grade 3 human obesity (862.5+222.0 pg/ml vs. 543.7+60.7 pg/ml in lean controls, p<0.001 and are positively correlated to the BMI (r = 0.43, p<0.0002. In the present study, bariatric surgery significantly altered serum BLyS concentrations. In contrast, weight loss due to a very-low-calorie-formula-diet (800 kcal/d had no such effect. To examine metabolic activity of BLyS, in a translational research approach, insulin sensitivity was measured in human subjects in vivo before and after treatment with the human recombinant anti-BLyS antibody belimumab. Since BLyS is known to promote B-cell proliferation and immunoglobulin secretion, the present data suggest that adipocytes of grade 3 obese human subjects are able to activate the adaptive immune system, suggesting that in metabolic inflammation in humans both, innate and adaptive immunity, are of pathophysiological relevance.

  20. Differential acute and chronic responses in insulin action in cultured myotubes following from nondiabetic severely obese humans following gastric bypass surgery.

    Science.gov (United States)

    Hinkley, J Matthew; Zou, Kai; Park, Sanghee; Zheng, Donghai; Dohm, G Lynis; Houmard, Joseph A

    2017-11-01

    Roux-en-Y gastric bypass (RYGB) surgery has been shown to induce positive metabolic adaptations for individuals with severe obesity (body mass index ≥40 kg/m 2 ), including improved peripheral insulin action. Although a major site of insulin action, the time course changes in skeletal muscle glucose metabolism following RYGB is unclear. To investigate the acute and chronic effects of RYGB surgery on insulin-stimulated glucose metabolism in cultured human primary myotubes derived from nondiabetic severely obese humans. East Carolina University Bariatric Surgery Center and East Carolina Diabetes and Obesity Institute. Primary human skeletal muscle cells were isolated from biopsies obtained from 8 women with severe obesity before, 1 month, and 7 months following RYGB surgery. Glucose metabolism, glycogen content, and insulin signal transduction were determined in differentiated myotubes. Insulin-stimulated glycogen synthesis and glucose oxidation increased in human myotubes derived from patients with severe obesity at both 1 and 7 months post-RYGB. However, there were no alterations indicative of enhanced insulin signal transduction. At 1 month post-RYGB, muscle glycogen levels were lower (-23%) and phosphorylation of acetyl CoA carboxylase 2 (ACC2) was elevated (+16%); both returned to presurgery levels at 7 months after RYGB in myotubes derived from patients. At 7 months post-RYGB, there was an increase in peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) protein content (+54%). These data indicate that insulin action intrinsically improves in cultured human primary myotubes derived from nondiabetic severely obese patients following RYGB surgery; however, the cellular alterations involved appear to consist of distinct acute and chronic components. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  1. Proteomics analysis of human skeletal muscle reveals novel abnormalities in obesity and type 2 diabetes

    DEFF Research Database (Denmark)

    Hwang, Hyonson; Bowen, Benjamin P; Lefort, Natalie

    2010-01-01

    changes involving the use of proteomics was used here. RESEARCH DESIGN AND METHODS: Muscle biopsies were obtained basally from lean, obese, and type 2 diabetic volunteers (n = 8 each); glucose clamps were used to assess insulin sensitivity. Muscle protein was subjected to mass spectrometry......OBJECTIVE : Insulin resistance in skeletal muscle is an early phenomenon in the pathogenesis of type 2 diabetes. Studies of insulin resistance usually are highly focused. However, approaches that give a more global picture of abnormalities in insulin resistance are useful in pointing out new...

  2. A Low-Glycemic Diet Lifestyle Intervention Improves Fat Utilization during Exercise in Older Obese Humans

    DEFF Research Database (Denmark)

    Solomon, Thomas; Haus, Jacob M; Cook, Marc A

    2013-01-01

    lipid was reduced (P loss intervention increased fat utilization during exercise independent of changes in energy expenditure. This highlights the potential therapeutic value of low-glycemic foods for reversing metabolic defects in obesity........ Results: Weight loss (-8.6 ± 1.1%) and improvements (P ... exchange ratio during exercise was unchanged in the LoGIX group but increased in the HiGIX group (P fat oxidation during exercise expressed in relation to changes in body weight was increased in the LoGIX group (+10.6 ± 3.6%; P

  3. Maternal obesity alters fatty acid oxidation, AMPK activity, and associated DNA methylation in mesenchymal stem cells from human infants

    Directory of Open Access Journals (Sweden)

    Kristen E. Boyle

    2017-11-01

    Conclusions: These data suggest that greater infant adiposity is associated with suppressed AMPK activity and reduced lipid oxidation in MSCs from infants born to mothers with obesity and may be an important, early marker of underlying obesity risk.

  4. Altered cytochrome P450 activities and expression levels in the liver and intestines of the monosodium glutamate-induced mouse model of human obesity.

    Science.gov (United States)

    Tomankova, Veronika; Liskova, Barbora; Skalova, Lenka; Bartikova, Hana; Bousova, Iva; Jourova, Lenka; Anzenbacher, Pavel; Ulrichova, Jitka; Anzenbacherova, Eva

    2015-07-15

    Cytochromes P450 (CYPs) are enzymes present from bacteria to man involved in metabolism of endogenous and exogenous compounds incl. drugs. Our objective was to assess whether obesity leads to changes in activities and expression of CYPs in the mouse liver, small intestine and colon. An obese mouse model with repeated injection of monosodium glutamate (MSG) to newborns was used. Controls were treated with saline. All mice were sacrificed at 8 months. In the liver and intestines, levels of CYP mRNA and proteins were analyzed using RT-PCR and Western blotting. Activities of CYP enzymes were measured with specific substrates of human orthologous forms. At the end of the experiment, body weight, plasma insulin and leptin levels as well as the specific content of hepatic CYP enzymes were increased in obese mice. Among CYP enzymes, hepatic CYP2A5 activity, protein and mRNA expression increased most significantly in obese animals. Higher activities and protein levels of hepatic CYP2E1 and 3A in the obese mice were also found. No or a weak effect on CYPs 2C and 2D was observed. In the small intestine and colon, no changes of CYP enzymes were detected except for increased expression of CYP2E1 and decreased expression of CYP3A mRNAs in the colon of the obese mice. Results of our study suggest that the specific content and activities of some liver CYP enzymes (especially CYP2A5) can be increased in obese mice. Higher activity of CYP2A5 (CYP2A6 human ortholog) could lead to altered metabolism of drug substrates of this enzyme (valproic acid, nicotine, methoxyflurane). Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Genetic fusion of human FGF21 to a synthetic polypeptide improves pharmacokinetics and pharmacodynamics in a mouse model of obesity.

    Science.gov (United States)

    Yin, Jun; Bao, Lichen; Tian, Hong; Wang, Qun; Gao, Xiangdong; Yao, Wenbing

    2016-07-01

    Chemical conjugation of therapeutic proteins with polyethylene glycol (PEG) is an established strategy to extend their biological half-life (t1/2 ) to a clinically useful range. We developed a novel uncharged and unstructured recombinant polypeptide composed of five amino acids (P, S, T, A and G), named PsTag, as another approach to extend the t1/2 of human FGF21, with increased hydrodynamic radius. Human FGF21 was fused with PsTag polymers of differing lengths (200 - 600 residues). Three fusion proteins and native FGF21 were produced in Escherichia coli. The biophysical characteristics, metabolic stability, immunogenicity and pharmacokinetics in were assessed in first. In lean and diet-induced obese (DIO) mice, effects on body weight, oral glucose tolerance tests and levels of relevant hormones and metabolites were studied. Fusion proteins were solubly expressed in E. coli and prolonged the t1/2 from 0.34h up to 12.9 h in mice. Fusion proteins were also biodegradable, thus avoiding vacuole formation, while lacking immunogenicity in mice. In DIO mice, administration of PsTag fused to FGF21 reduced body weight, blood glucose and lipids levels and reversed hepatic steatosis. The novel recombinant polypeptide, PsTag, should be useful in the development of biological drugs with properties comparable to those achievable by PEGylation, but with potentially less side effects. In mice, fusion of FGF21 to PsTag prolonged and potentiated pharmacological effects of native FGF21, and may offer greater therapeutic effects in treatment of obesity. © 2016 The British Pharmacological Society.

  6. Brown-Like Adipocyte Progenitors Derived from Human iPS Cells: A New Tool for Anti-obesity Drug Discovery and Cell-Based Therapy?

    Science.gov (United States)

    Yao, Xi; Salingova, Barbara; Dani, Christian

    2018-04-10

    Alternative strategies are urgently required to fight obesity and associated metabolic disorders including diabetes and cardiovascular diseases. Brown and brown-like adipocytes (BAs) store fat, but in contrast to white adipocytes, activated BAs are equipped to dissipate energy stored. Therefore, BAs represent promising cell targets to counteract obesity. However, the scarcity of BAs in adults is a major limitation for a BA-based therapy of obesity, and the notion to increase the BA mass by transplanting BA progenitors (BAPs) in obese patients recently emerged. The next challenge is to identify an abundant and reliable source of BAPs. In this chapter, we describe the capacity of human-induced pluripotent stem cells (hiPSCs) to generate BAPs able to differentiate at a high efficiency with no gene transfer. This cell model represents an unlimited source of human BAPs that in a near future may be a suitable tool for both therapeutic transplantation and for the discovery of novel efficient and safe anti-obesity drugs. The generation of a relevant cell model, such as hiPSC-BAs in 3D adipospheres enriched with macrophages and endothelial cells to better mimic the microenvironment within the adipose tissue, will be the next critical step.

  7. Genome-Wide Association Study Reveals Genetic Architecture of Eating Behaviors in Pigs and its Implications for Humans Obesity by Comparative Genome Mapping

    DEFF Research Database (Denmark)

    Do, Duy Ngoc; Strathe, Anders Bjerring; Ostersen, Tage

    2013-01-01

    This study was aimed at identifying genomic regions controlling feeding behaviors inDanish Duroc boars and its potential implications for eating behaviors in humans.Individual daily feed intake (DFI), total daily time spent in feeder (TPD), number of dailyvisits to feeder (NVD), time spent to eat...... for geneticimprovement of pig feed efficiency. The results of pig-human comparative genemapping revealed some important genomic regions and/or genes on the humangenome that may influence eating behavior in human and consequently affect thedevelopment of obesity and metabolic syndromes. This is the first...... such translationalgenomics study to report potential candidate genes for eating behavior in humans...

  8. Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects-A Narrative Review of Human and Animal Evidence.

    Science.gov (United States)

    Harvie, Michelle; Howell, Anthony

    2017-01-19

    Intermittent energy restriction (IER) has become popular as a means of weight control amongst people who are overweight and obese, and is also undertaken by normal weight people hoping spells of marked energy restriction will optimise their health. This review summarises randomised comparisons of intermittent and isoenergetic continuous energy restriction for weight loss to manage overweight and obesity. It also summarises the potential beneficial or adverse effects of IER on body composition, adipose stores and metabolic effects from human studies, including studies amongst normal weight subjects and relevant animal experimentation. Six small short term (benefits or harms of IER amongst people who are overweight or obese, and particularly amongst normal weight subjects, is not known and is a priority for further investigation.

  9. Proteomics reveals changes in hepatic proteins during chicken embryonic development: an alternative model to study human obesity.

    Science.gov (United States)

    Peng, Mengling; Li, Shengnan; He, Qianian; Zhao, Jinlong; Li, Longlong; Ma, Haitian

    2018-01-08

    Chicken embryos are widely used as a model for studies of obesity; however, no detailed information is available about the dynamic changes of proteins during the regulation of adipose biology and metabolism. Thus, the present study used an isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic approach to identify the changes in protein abundance at different stages of chicken embryonic development. In this study, the abundances of 293 hepatic proteins in 19-day old of chicken embryos compared with 14-day old and 160 hepatic proteins at hatching compared with 19-day old embryos were significantly changed. Pathway analysis showed that fatty acid degradation (upregulated ACAA2, CPT1A, and ACOX1), protein folding (upregulated PDIs, CALR3, LMAN1, and UBQLN1) and gluconeogenesis (upregulated ACSS1, AKR1A1, ALDH3A2, ALDH7A1, and FBP2) were enhanced from embryonic day 14 (E14) to E19 of chicken embryo development. Analysis of the differentially abundant proteins indicated that glycolysis was not the main way to produce energy from E19 to hatching day during chicken embryo development. In addition, purine metabolism was enhanced, as deduced from increased IMPDH2, NT5C, PGM2, and XDH abundances, and the decrease of growth rate could be overcome by increasing the abundance of ribosomal proteins from E19 to the hatching day. The levels of certain proteins were coordinated with each other to regulate the changes in metabolic pathways to satisfy the requirement for growth and development at different stages of chicken embryo development. Importantly, ACAA2, CPT1A, and ACOX1 might be key factors to control fat deposition during chicken embryonic development. These results provided information showing that chicken is a useful model to further investigate the mechanism of obesity and insulin resistance in humans.

  10. Gene-chip studies of adipogenesis-regulated microRNAs in mouse primary adipocytes and human obesity

    Directory of Open Access Journals (Sweden)

    Gallagher Iain J

    2011-03-01

    Full Text Available Abstract Background Adipose tissue abundance relies partly on the factors that regulate adipogenesis, i.e. proliferation and differentiation of adipocytes. While components of the transcriptional program that initiates adipogenesis is well-known, the importance of microRNAs in adipogenesis is less well studied. We thus set out to investigate whether miRNAs would be actively modulated during adipogenesis and obesity. Methods Several models exist to study adipogenesis in vitro, of which the cell line 3T3-L1 is the most well known, albeit not the most physiologically appropriate. Thus, as an alternative, we produced EXIQON microarray of brown and white primary murine adipocytes (prior to and following differentiation to yield global profiles of miRNAs. Results We found 65 miRNAs regulated during in vitro adipogenesis in primary adipocytes. We evaluated the similarity of our responses to those found in non-primary cell models, through literature data-mining. When comparing primary adipocyte profiles, with those of cell lines reported in the literature, we found a high degree of difference in 'adipogenesis' regulated miRNAs suggesting that the model systems may not be accurately representing adipogenesis. The expression of 10 adipogenesis-regulated miRNAs were studied using real-time qPCR and then we selected 5 miRNAs, that showed robust expression, were profiled in subcutaneous adipose tissue obtained from 20 humans with a range of body mass indices (BMI, range = 21-48, and all samples have U133+2 Affymetrix profiles provided. Of the miRNAs tested, mir-21 was robustly expressed in human adipose tissue and positively correlated with BMI (R2 = 0.49, p Conclusion In conclusion, we provide a preliminary analysis of miRNAs associated with primary cell in vitro adipogenesis and demonstrate that the inflammation-associated miRNA, mir-21 is up-regulated in subcutaneous adipose tissue in human obesity. Further, we provide a novel transcriptomics database of

  11. Obesity and physical activity.

    NARCIS (Netherlands)

    Westerterp, K.R.

    1999-01-01

    Department of Human Biology, Maastricht University, The Netherlands. k.westerterp@hb.unimaas.nl OBJECTIVES: Three aspects of obesity and physical activity are reviewed: whether the obese are inactive; how the activity level can be increased; and which are the effects of an increase in physical

  12. Oral insulin (human, murine, or porcine) does not prevent diabetes in the non-obese diabetic mouse.

    Science.gov (United States)

    Pham, Minh N; Gibson, Claire; Rydén, Anna K E; Perdue, Nikole; Boursalian, Tamar E; Pagni, Philippe P; Coppieters, Ken; Skonberg, Christian; Porsgaard, Trine; von Herrath, Matthias; Vela, Jose Luis

    2016-03-01

    Studies have shown oral insulin prevents type 1 diabetes (T1D) in mouse models, however human trials were inconclusive. We tested the ability of different insulins to prevent T1D in non-obese diabetic mice. Mice received oral insulin or PBS twice weekly and disease was monitored. Contrary to previous studies, no insulin tested showed significant ability to prevent T1D, nor did testing of linked suppression in a delayed type hypersensitivity model have reproducible effect. To investigate delivery of antigen within the GI tract, blue dye was fed to mice. Dye traveled 5-8 cm from stomach to small intestine within 10s, suggesting orally administered antigen may not get digested in the stomach in mice. Insulin incubated with jejunum extracts was instantly digested. Thus, in humans large doses of insulin may be required to achieve tolerance as antigen may be more vulnerable to digestion in the stomach even before reaching the small intestine. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Lansoprazole enhances the antidiabetic effect of sitagliptin in mice with diet-induced obesity and healthy human subjects.

    Science.gov (United States)

    Hao, ShaoJun; Sun, JianHua; Tian, XiKui; Sun, Xu; Zhang, ZhenXing; Gao, Yuan

    2014-08-01

    Proton pump inhibitors as adjunctive therapy would improve diabetes control and could enhance the hypoglycaemic activity of DPP-4 inhibitors. The aim of the study was to investigate the short-term effects of lansoprazole (LPZ), sitagliptin (SITA) and their combination therapy on glucose regulation and gut peptide secretion. Glucose and gut peptide were determined and compared after short-term administration of LPZ or SITA, or in combination to mice with diet-induced obesity (DIO) and to healthy human subjects (n = 16) in a 75 g oral glucose tolerance test (OGTT) by a crossover design. In DIO mice, LPZ significantly improve glucose metabolism, increase plasma C-peptide and insulin compared with vehicle treatment. Furthermore, the combination of LPZ and SITA improved glucose tolerance additively, with higher plasma insulin and C-peptide levels compared with SITA-treated mice. Similarly, in human in the OGTT, the combination showed significant improvement in glucose-lowering and insulin increase vs SITA-treated group. However, no significant differences in area under curve (AUC) of insulin, glucose and C-peptide between the LPZ-treated group and baseline, except that mean AUCgastrin was significantly increased by LPZ. LPZ and SITA combination therapy appears to have complementary mechanisms of action and additive antidiabetic effect. © 2014 Royal Pharmaceutical Society.

  14. Sexually dimorphic functional connectivity in response to high vs. low energy-dense food cues in obese humans: an fMRI study.

    Science.gov (United States)

    Atalayer, Deniz; Pantazatos, Spiro P; Gibson, Charlisa D; McOuatt, Haley; Puma, Lauren; Astbury, Nerys M; Geliebter, Allan

    2014-10-15

    Sexually-dimorphic behavioral and biological aspects of human eating have been described. Using psychophysiological interaction (PPI) analysis, we investigated sex-based differences in functional connectivity with a key emotion-processing region (amygdala, AMG) and a key reward-processing area (ventral striatum, VS) in response to high vs. low energy-dense (ED) food images using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in obese persons in fasted and fed states. When fed, in response to high vs. low-ED food cues, obese men (vs. women) had greater functional connectivity with AMG in right subgenual anterior cingulate, whereas obese women had greater functional connectivity with AMG in left angular gyrus and right primary motor areas. In addition, when fed, AMG functional connectivity with pre/post-central gyrus was more associated with BMI in women (vs. men). When fasted, obese men (vs. women) had greater functional connectivity with AMG in bilateral supplementary frontal and primary motor areas, left precuneus, and right cuneus, whereas obese women had greater functional connectivity with AMG in left inferior frontal gyrus, right thalamus, and dorsomedial prefrontal cortex. When fed, greater functional connectivity with VS was observed in men in bilateral supplementary and primary motor areas, left postcentral gyrus, and left precuneus. These sex-based differences in functional connectivity in response to visual food cues may help partly explain differential eating behavior, pathology prevalence, and outcomes in men and women. Published by Elsevier Inc.

  15. Caloric Restriction and Diet-Induced Weight Loss Do Not Induce Browning of Human Subcutaneous White Adipose Tissue in Women and Men with Obesity

    Directory of Open Access Journals (Sweden)

    Valentin Barquissau

    2018-01-01

    Full Text Available Caloric restriction (CR is standard lifestyle therapy in obesity management. CR-induced weight loss improves the metabolic profile of individuals with obesity. In mice, occurrence of beige fat cells in white fat depots favors a metabolically healthy phenotype, and CR promotes browning of white adipose tissue (WAT. Here, human subcutaneous abdominal WAT samples were analyzed in 289 individuals with obesity following a two-phase dietary intervention consisting of an 8 week very low calorie diet and a 6-month weight-maintenance phase. Before the intervention, we show sex differences and seasonal variation, with higher expression of brown and beige markers in women with obesity and during winter, respectively. The very low calorie diet resulted in decreased browning of subcutaneous abdominal WAT. During the whole dietary intervention, evolution of body fat and insulin resistance was independent of changes in brown and beige fat markers. These data suggest that diet-induced effects on body fat and insulin resistance are independent of subcutaneous abdominal WAT browning in people with obesity.

  16. Evaluating the evidence for macrophage presence in skeletal muscle and its relation to insulin resistance in obese mice and humans: a systematic review protocol.

    Science.gov (United States)

    Bhatt, Meha; Rudrapatna, Srikesh; Banfield, Laura; Bierbrier, Rachel; Wang, Pei-Wen; Wang, Kuan-Wen; Thabane, Lehana; Samaan, M Constantine

    2017-08-08

    The current global rates of obesity and type 2 diabetes are staggering. In order to implement effective management strategies, it is imperative to understand the mechanisms of obesity-induced insulin resistance and diabetes. Macrophage infiltration and inflammation of the adipose tissue in obesity is a well-established paradigm, yet the role of macrophages in muscle inflammation, insulin resistance and diabetes is not adequately studied. In this systematic review, we will examine the evidence for the presence of macrophages in skeletal muscle of obese humans and mice, and will assess the association between muscle macrophages and insulin resistance. We will identify published studies that address muscle macrophage content and phenotype, and its association with insulin resistance. We will search MEDLINE/PubMed, EMBASE, and Web of Science for eligible studies. Grey literature will be searched in ProQuest. Quality assessment will be conducted using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias Tool for animal studies. The findings of this systematic review will shed light on immune-metabolic crosstalk in obesity, and allow the consideration of targeted therapies to modulate muscle macrophages in the treatment and prevention of diabetes. The review will be published in a peer-reviewed journal and presented at conferences.

  17. Asymmetric dimethylarginine (ADMA) elevation and arginase up-regulation contribute to endothelial dysfunction related to insulin resistance in rats and morbidly obese humans.

    Science.gov (United States)

    El Assar, Mariam; Angulo, Javier; Santos-Ruiz, Marta; Ruiz de Adana, Juan Carlos; Pindado, María Luz; Sánchez-Ferrer, Alberto; Hernández, Alberto; Rodríguez-Mañas, Leocadio

    2016-06-01

    The presence of insulin resistance (IR) is determinant for endothelial dysfunction associated with obesity. Although recent studies have implicated the involvement of mitochondrial superoxide and inflammation in the defective nitric oxide (NO)-mediated responses and subsequent endothelial dysfunction in IR, other mechanisms could compromise this pathway. In the present study, we assessed the role of asymmetric dimethylarginine (ADMA) and arginase with respect to IR-induced impairment of endothelium-dependent vasodilatation in human morbid obesity and in a non-obese rat model of IR. We show that both increased ADMA and up-regulated arginase are determinant factors in the alteration of the l-arginine/NO pathway associated with IR in both models and also that acute treatment of arteries with arginase inhibitor or with l-arginine significantly alleviate endothelial dysfunction. These results help to expand our knowledge regarding the mechanisms of endothelial dysfunction that are related to obesity and IR and establish potential therapeutic targets for intervention. Insulin resistance (IR) is determinant for endothelial dysfunction in human obesity. Although we have previously reported the involvement of mitochondrial superoxide and inflammation, other mechanisms could compromise NO-mediated responses in IR. We evaluated the role of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) and arginase with respect to IR-induced impairment of l-arginine/NO-mediated vasodilatation in human morbid obesity and in a non-obese rat model of IR. Bradykinin-induced vasodilatation was evaluated in microarteries derived from insulin-resistant morbidly obese (IR-MO) and non-insulin-resistant MO (NIR-MO) subjects. Defective endothelial vasodilatation in IR-MO was improved by l-arginine supplementation. Increased levels of ADMA were detected in serum and adipose tissue from IR-MO. Serum ADMA positively correlated with IR score and negatively with pD2 for bradykinin. Gene

  18. Asymmetric dimethylarginine (ADMA) elevation and arginase up‐regulation contribute to endothelial dysfunction related to insulin resistance in rats and morbidly obese humans

    Science.gov (United States)

    El Assar, Mariam; Angulo, Javier; Santos‐Ruiz, Marta; Ruiz de Adana, Juan Carlos; Pindado, María Luz; Sánchez‐Ferrer, Alberto; Hernández, Alberto

    2016-01-01

    Key points The presence of insulin resistance (IR) is determinant for endothelial dysfunction associated with obesity.Although recent studies have implicated the involvement of mitochondrial superoxide and inflammation in the defective nitric oxide (NO)‐mediated responses and subsequent endothelial dysfunction in IR, other mechanisms could compromise this pathway.In the present study, we assessed the role of asymmetric dimethylarginine (ADMA) and arginase with respect to IR‐induced impairment of endothelium‐dependent vasodilatation in human morbid obesity and in a non‐obese rat model of IR.We show that both increased ADMA and up‐regulated arginase are determinant factors in the alteration of the l‐arginine/NO pathway associated with IR in both models and also that acute treatment of arteries with arginase inhibitor or with l‐arginine significantly alleviate endothelial dysfunction.These results help to expand our knowledge regarding the mechanisms of endothelial dysfunction that are related to obesity and IR and establish potential therapeutic targets for intervention. Abstract Insulin resistance (IR) is determinant for endothelial dysfunction in human obesity. Although we have previously reported the involvement of mitochondrial superoxide and inflammation, other mechanisms could compromise NO‐mediated responses in IR. We evaluated the role of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) and arginase with respect to IR‐induced impairment of l‐arginine/NO‐mediated vasodilatation in human morbid obesity and in a non‐obese rat model of IR. Bradykinin‐induced vasodilatation was evaluated in microarteries derived from insulin‐resistant morbidly obese (IR‐MO) and non‐insulin‐resistant MO (NIR‐MO) subjects. Defective endothelial vasodilatation in IR‐MO was improved by l‐arginine supplementation. Increased levels of ADMA were detected in serum and adipose tissue from IR‐MO. Serum ADMA positively correlated with

  19. Pediatric Obesity: Etiology and Treatment

    OpenAIRE

    Crocker, Melissa K.; Yanovski, Jack A.

    2009-01-01

    This paper reviews factors that contribute to excessive weight gain in children and outlines current knowledge regarding approaches for treating pediatric obesity. Virtually all of the known genetic causes of obesity primarily increase energy intake. Genes regulating the leptin signaling pathway are particularly important for human energy homeostasis. Obesity is a chronic disorder that requires long-term strategies for management. The foundation for all treatments for pediatric obesity remain...

  20. Bofu-tsu-shosan, an oriental herbal medicine, exerts a combinatorial favorable metabolic modulation including antihypertensive effect on a mouse model of human metabolic disorders with visceral obesity.

    Directory of Open Access Journals (Sweden)

    Kengo Azushima

    Full Text Available Accumulating evidence indicates that metabolic dysfunction with visceral obesity is a major medical problem associated with the development of hypertension, type 2 diabetes (T2DM and dyslipidemia, and ultimately severe cardiovascular and renal disease. Therefore, an effective anti-obesity treatment with a concomitant improvement in metabolic profile is important for the treatment of metabolic dysfunction with visceral obesity. Bofu-tsu-shosan (BOF is one of oriental herbal medicine and is clinically available to treat obesity in Japan. Although BOF is a candidate as a novel therapeutic strategy to improve metabolic dysfunction with obesity, the mechanism of its beneficial effect is not fully elucidated. Here, we investigated mechanism of therapeutic effects of BOF on KKAy mice, a model of human metabolic disorders with obesity. Chronic treatment of KKAy mice with BOF persistently decreased food intake, body weight gain, low-density lipoprotein cholesterol and systolic blood pressure. In addition, both tissue weight and cell size of white adipose tissue (WAT were decreased, with concomitant increases in the expression of adiponectin and peroxisome proliferator-activated receptors genes in WAT as well as the circulating adiponectin level by BOF treatment. Furthermore, gene expression of uncoupling protein-1, a thermogenesis factor, in brown adipose tissue and rectal temperature were both elevated by BOF. Intriguingly, plasma acylated-ghrelin, an active form of orexigenic hormone, and short-term food intake were significantly decreased by single bolus administration of BOF. These results indicate that BOF exerts a combinatorial favorable metabolic modulation including antihypertensive effect, at least partially, via its beneficial effect on adipose tissue function and its appetite-inhibitory property through suppression on the ghrelin system.

  1. Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection.

    LENUS (Irish Health Repository)

    O'Shea, D

    2013-02-26

    Dendritic cells (DCs) are key immune sentinels linking the innate and adaptive immune systems. DCs recognise danger signals and initiate T-cell tolerance, memory and polarisation. They are critical cells in responding to a viral illness. Obese individuals have been shown to have an impaired response to vaccinations against virally mediated conditions and to have an increased susceptibility to multi-organ failure in response to viral illness. We investigated if DCs are altered in an obese cohort (mean body mass index 51.7±7.3 kg m(-2)), ultimately resulting in differential T-cell responses. Circulating DCs were found to be significantly decreased in the obese compared with the lean cohort (0.82% vs 2.53%). Following Toll-like receptor stimulation, compared with lean controls, DCs generated from the obese cohort upregulated significantly less CD83 (40% vs 17% mean fluorescence intensity), a molecule implicated in the elicitation of T-cell responses, particularly viral responses. Obese DCs produced twofold more of the immunosuppressive cytokine interleukin (IL)-10 than lean controls, and in turn stimulated fourfold more IL-4-production from allogenic naive T cells. We conclude that obesity negatively impacts the ability of DCs to mature and elicit appropriate T-cell responses to a general stimulus. This may contribute to the increased susceptibility to viral infection observed in severe obesity.International Journal of Obesity advance online publication, 26 February 2013; doi:10.1038\\/ijo.2013.16.

  2. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans

    NARCIS (Netherlands)

    Timmers, Silvie; Konings, Ellen; Bilet, Lena; Houtkooper, Riekelt H.; van de Weijer, Tineke; Goossens, Gijs H.; Hoeks, Joris; van der Krieken, Sophie; Ryu, Dongryeol; Kersten, Sander; Moonen-Kornips, Esther; Hesselink, Matthijs K. C.; Kunz, Iris; Schrauwen-Hinderling, Vera B.; Blaak, Ellen E.; Auwerx, Johan; Schrauwen, Patrick

    2011-01-01

    Resveratrol is a natural compound that affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here, we treated 11 healthy, obese men with placebo and 150 mg/day resveratrol (resVida) in a randomized double-blind

  3. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans

    NARCIS (Netherlands)

    Timmers, Silvie; Konings, Ellen; Bilet, Lena; Houtkooper, Riekelt H.; Weijer, van de Tineke; Hoeks, Joris; Krieken, van der Sophie; Ryu, Dongryeol; Kersten, Sander; Moonen-Kornips, Esther; Goossens, Gijs H.; Hesselink, Matthijs K.; Kunz, Iris; Schrauwen-Hinderling, Vera B.; Blaak, Ellen E.; Auwerx, Johan; Schrauwen, Patrick

    2011-01-01

    Resveratrol is a naturally occurring compound that profoundly affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here we treated 10 healthy, obese men with placebo and 150 mg/day resveratrol in a randomized

  4. Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans

    NARCIS (Netherlands)

    Timmers, S.; Konings, E.; Bilet, L.; Houtkooper, R.H.; Weijer, van de T.; Goossens, G.H.; Hoeks, J.; Krieken, van der S.; Ryu, D.; Kersten, A.H.; Moonen-Kornips, E.; Hesselink, M.K.C.; Kunz, I.; Schrauwen-Hinderling, V.B.; Blaak, E.E.; Auwerx, J.; Schrauwen, P.

    2011-01-01

    Resveratrol is a natural compound that affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here, we treated 11 healthy, obese men with placebo and 150 mg/day resveratrol (resVida) in a randomized double-blind

  5. Lipid mobilization in subcutaneous adipose tissue during exercise in lean and obese humans. Roles of insulin and natriuretic peptides

    DEFF Research Database (Denmark)

    Koppo, Katrien; Larrouy, Dominique; Marques, Marie A

    2010-01-01

    The aim of this study was to evaluate the relative contributions of various hormones involved in the regulation of lipid mobilization in subcutaneous adipose tissue (SCAT) during exercise and to assess the impact of obesity on this regulation. Eight lean and eight obese men performed a 60-min cyc...

  6. The influence of obesity on the effects of spirulina supplementation in the human metabolic response of Korean elderly.

    Science.gov (United States)

    Park, Hee-Jung; Lee, Hyun-Sook

    2016-08-01

    Spirulina, a blue-green alga, is widely produced and commercialized as a dietary supplement with bio- and immune-modulatory functions. We have previously shown that spirulina had favorable effects on lipid profiles, immune functions, and antioxidant capacity in healthy Korean elderly. Despite favorable effect of spirulina supplementation, some sub-populations have shown a poor response to supplementation. Obesity is a factor related to poor-response. Therefore, the purpose of this study was to determine the immuno-modulation, antioxidant capacity, and lipid-lowering effect of spirulina in obese and non-obese Korean elderly. The subjects were 78 elderly aged 60-87 years. In a randomized double blind, placebo-controlled study, subjects were fed either placebo or spirulina daily, at 8 g for 12 weeks. Subjects were divided into the non-obese group and the obese group based on body mass index (BMI) criteria for Asians suggested by the International Obesity Task Force: BMI effect on plasma concentration of total cholesterol and LDL-cholesterol, a significant increase in interleukin (IL)-2 concentration (P effects were not observed in the obese group. These results demonstrated that blood lipid lowering and immune and antioxidant improving response for spirulina supplement was affected by obesity in Korean elderly.

  7. “Infectobesity: viral infections (especially with human adenovirus-36: Ad-36) may be a cause of obesity

    NARCIS (Netherlands)

    Ginneken, van V.J.T.; Sitnyakowsky, L.; Jeffery, J.E.

    2009-01-01

    In recent years viral infections have been recognized as possible cause of obesity, alongside the traditionally recognized causes (genetic inheritance, and behaviour/environmental causes such as diet exercise, cultural practices and stress). Although four viruses have been reported to induce obesity

  8. Treating Diet-Induced Diabetes and Obesity with Human Embryonic Stem Cell-Derived Pancreatic Progenitor Cells and Antidiabetic Drugs

    Directory of Open Access Journals (Sweden)

    Jennifer E. Bruin

    2015-04-01

    Full Text Available Human embryonic stem cell (hESC-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported. An immunodeficient model of type 2 diabetes was generated by high-fat diet (HFD feeding in SCID-beige mice. Exposure to HFDs did not impact the maturation of macroencapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in HFD-fed transplant recipients after 24 weeks. However, since diet-induced hyperglycemia and obesity were not fully ameliorated by transplantation alone, a second cohort of HFD-fed mice was treated with pancreatic progenitor cells combined with one of three antidiabetic drugs. All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks. Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs.

  9. Genome-wide Linkage Disequilibrium Linkage Analysis (LDLA) of Body Fat Traits in an F2 Porcine Model for Human Obesity

    DEFF Research Database (Denmark)

    Pant, Sameer Dinkar; Karlskov-Mortensen, Peter; Cirera Salicio, Susanna

    , body composition was determined at about two months of age (64 ± 11 days) via dual-energy xray absorptiometry (DXA) scanning. All pigs were genotyped using Illumina Porcine 60k SNP Beadchip and a combined LDLA approach was used to perform genomewide linkage and association analysis for body fat traits...... provide novel insights that may further the current understanding of the molecular mechanisms underlying human obesity....

  10. Reduced UCP-1 content in in vitro differentiated beige/brite adipocytes derived from preadipocytes of human subcutaneous white adipose tissues in obesity.

    Directory of Open Access Journals (Sweden)

    Andrew L Carey

    Full Text Available Brown adipose tissue (BAT is a potential therapeutic target to reverse obesity. The purpose of this study was to determine whether primary precursor cells isolated from human adult subcutaneous white adipose tissue (WAT can be induced to differentiate in-vitro into adipocytes that express key markers of brown or beige adipose, and whether the expression level of such markers differs between lean and obese young adult males.Adipogenic precursor cells were isolated from lean and obese individuals from subcutaneous abdominal WAT biopsies. Cells were grown to confluence, differentiated for 2.5 weeks then harvested for measurement of gene expression and UCP1 protein.There was no difference between groups with respect to differentiation into adipocytes, as indicated by oil red-O staining, rates of lipolysis, and expression of adipogenic genes (FABP4, PPARG. WAT genes (HOXC9, RB1 were expressed equally in the two groups. Post differentiation, the beige adipose specific genes CITED1 and CD137 were significantly increased in both groups, but classic BAT markers ZIC1 and LHX8 decreased significantly. Cell lines from both groups also equally increased post-differentiation expression of the thermogenic-responsive gene PPARGC1A (PGC-1α. UCP1 gene expression was undetectable prior to differentiation, however after differentiation both gene expression and protein content were increased in both groups and were significantly greater in cultures from lean compared with obese individuals (p<0.05.Human subcutaneous WAT cells can be induced to attain BAT characteristics, but this capacity is reduced in WAT cells from obese individuals.

  11. Obesity and infection: reciprocal causality.

    Science.gov (United States)

    Hainer, V; Zamrazilová, H; Kunešová, M; Bendlová, B; Aldhoon-Hainerová, I

    2015-01-01

    Associations between different infectious agents and obesity have been reported in humans for over thirty years. In many cases, as in nosocomial infections, this relationship reflects the greater susceptibility of obese individuals to infection due to impaired immunity. In such cases, the infection is not related to obesity as a causal factor but represents a complication of obesity. In contrast, several infections have been suggested as potential causal factors in human obesity. However, evidence of a causal linkage to human obesity has only been provided for adenovirus 36 (Adv36). This virus activates lipogenic and proinflammatory pathways in adipose tissue, improves insulin sensitivity, lipid profile and hepatic steatosis. The E4orf1 gene of Adv36 exerts insulin senzitizing effects, but is devoid of its pro-inflammatory modalities. The development of a vaccine to prevent Adv36-induced obesity or the use of E4orf1 as a ligand for novel antidiabetic drugs could open new horizons in the prophylaxis and treatment of obesity and diabetes. More experimental and clinical studies are needed to elucidate the mutual relations between infection and obesity, identify additional infectious agents causing human obesity, as well as define the conditions that predispose obese individuals to specific infections.

  12. Different effects of hyperlipidic diets in human lactation and adulthood: growth versus the development of obesity

    Directory of Open Access Journals (Sweden)

    Alemany Marià

    2011-07-01

    Full Text Available Abstract After birth, the body shifts from glucose as primary energy substrate to milk-derived fats, with sugars from lactose taking a secondary place. At weaning, glucose recovers its primogeniture and dietary fat role decreases. In spite of human temporary adaptation to a high-fat (and sugars and protein diet during lactation, the ability to thrive on this type of diet is lost irreversibly after weaning. We could not revert too the lactating period metabolic setting because of different proportions of brain/muscle metabolism in the total energy budget, lower thermogenesis needs and capabilities, and absence of significant growth in adults. A key reason for change was the limited availability of foods with high energy content at weaning and during the whole adult life of our ancestors, which physiological adaptations remain practically unchanged in our present-day bodies. Humans have evolved to survive with relatively poor diets interspersed by bouts of scarcity and abundance. Today diets in many societies are largely made up from choice foods, responding to our deeply ingrained desire for fats, protein, sugars, salt etc. Consequently our diets are not well adjusted to our physiological needs/adaptations but mainly to our tastes (another adaptation to periodic scarcity, and thus are rich in energy roughly comparable to milk. However, most adult humans cannot process the food ingested in excess because our cortical-derived craving overrides the mechanisms controlling appetite. This is produced not because we lack the biochemical mechanisms to use this energy, but because we are unprepared for excess, and wholly adapted to survive scarcity. The thrifty mechanisms compound the effects of excess nutrients and damage the control of energy metabolism, developing a pathologic state. As a consequence, an overflow of energy is generated and the disease of plenty develops.

  13. Accurate identification of neutralizing antibodies to adenovirus Ad36, -a putative contributor of obesity in humans.

    Science.gov (United States)

    Dubuisson, Olga; Day, Rena Sue; Dhurandhar, Nikhil V

    2015-01-01

    In children and adults, human adenovirus serotype 36 (Ad36) is linked with increased adiposity, and important metabolic alterations. Since this property is not shared by many other human adenovirus serotypes, it is imperative to specifically identify exposure to Ad36. Although serum neutralization assay (SNA) is the gold standard to specifically detect neutralizing antibodies (NA) to Ad36, it requires 2-weeks to complete and considerable training to interpret the results. Whereas, an enzyme-immuno assay (EIA) may provide a quicker and objective determination. Evaluate the accuracy of commercially available EIA kits to detect NA to Ad36. Modify SNA to reduce time and increase objectivity. Sera of 15 seropositive or 16 seronegative subjects confirmed by SNA were used to test: 1) reproducibility of SNA to detect Ad36 exposure, by repeating assays twice; 2) an EIA that detects antibodies to all human adenovirus serotypes (NS-EIA) (Abcam-108705); 3) an EIA supposedly specific for Ad36 antibody (Ad36-EIA) (MyBioSource,#MBS705802), and 4) the concordance of SNA with a novel combination of SNA and immune-staining (SN-IS) kit (Cell BioLabs,#VPK-111). The SNA showed exact reproducibility. NS-EIA detected adenovirus antibodies in 94% samples, confirming the non-specificity of the assay for Ad36 serotype. All seronegative samples (as determined by SNA) were false positive by Ad36-EIA. In 97% samples, SN-IS showed fidelity with Ad36-antibody status as determined by SNA. The available EIA kits are not specific for detecting NA to Ad36. The modified SNA with immune-staining reduces assay time and increases accuracy of detecting by reducing subjectivity. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Short-chain fructo-oligosaccharides modulate intestinal microbiota and metabolic parameters of humanized gnotobiotic diet induced obesity mice.

    Directory of Open Access Journals (Sweden)

    Frederique Respondek

    Full Text Available Prebiotic fibres like short-chain fructo-oligosaccharides (scFOS are known to selectively modulate the composition of the intestinal microbiota and especially to stimulate Bifidobacteria. In parallel, the involvement of intestinal microbiota in host metabolic regulation has been recently highlighted. The objective of the study was to evaluate the effect of scFOS on the composition of the faecal microbiota and on metabolic parameters in an animal model of diet-induced obesity harbouring a human-type microbiota. Forty eight axenic C57BL/6J mice were inoculated with a sample of faecal human microbiota and randomly assigned to one of 3 diets for 7 weeks: a control diet, a high fat diet (HF, 60% of energy derived from fat or an isocaloric HF diet containing 10% of scFOS (HF-scFOS. Mice fed with the two HF gained at least 21% more weight than mice from the control group. Addition of scFOS partially abolished the deposition of fat mass but significantly increased the weight of the caecum. The analysis of the taxonomic composition of the faecal microbiota by FISH technique revealed that the addition of scFOS induced a significant increase of faecal Bifidobacteria and the Clostridium coccoides group whereas it decreased the Clostridium leptum group. In addition to modifying the composition of the faecal microbiota, scFOS most prominently affected the faecal metabolome (e.g. bile acids derivatives, hydroxyl monoenoic fatty acids as well as urine, plasma hydrophilic and plasma lipid metabolomes. The increase in C. coccoides and the decrease in C. leptum, were highly correlated to these metabolic changes, including insulinaemia, as well as to the weight of the caecum (empty and full but not the increase in Bifidobacteria. In conclusion scFOS induce profound metabolic changes by modulating the composition and the activity of the intestinal microbiota, that may partly explain their effect on the reduction of insulinaemia.

  15. Biology of Obesity: Lessons from Animal Models of Obesity

    Directory of Open Access Journals (Sweden)

    Keizo Kanasaki

    2011-01-01

    problems, including diabetes, cardiovascular disease, respiratory failure, muscle weakness, and cancer. The precise molecular mechanisms by which obesity induces these health problems are not yet clear. To better understand the pathomechanisms of human disease, good animal models are essential. In this paper, we will analyze animal models of obesity and their use in the research of obesity-associated human health conditions and diseases such as diabetes, cancer, and obstructive sleep apnea syndrome.

  16. Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects—A Narrative Review of Human and Animal Evidence

    Directory of Open Access Journals (Sweden)

    Michelle Harvie

    2017-01-01

    Full Text Available Intermittent energy restriction (IER has become popular as a means of weight control amongst people who are overweight and obese, and is also undertaken by normal weight people hoping spells of marked energy restriction will optimise their health. This review summarises randomised comparisons of intermittent and isoenergetic continuous energy restriction for weight loss to manage overweight and obesity. It also summarises the potential beneficial or adverse effects of IER on body composition, adipose stores and metabolic effects from human studies, including studies amongst normal weight subjects and relevant animal experimentation. Six small short term (<6 month studies amongst overweight or obese individuals indicate that intermittent energy restriction is equal to continuous restriction for weight loss, with one study reporting greater reductions in body fat, and two studies reporting greater reductions in HOMA insulin resistance in response to IER, with no obvious evidence of harm. Studies amongst normal weight subjects and different animal models highlight the potential beneficial and adverse effects of intermittent compared to continuous energy restriction on ectopic and visceral fat stores, adipocyte size, insulin resistance, and metabolic flexibility. The longer term benefits or harms of IER amongst people who are overweight or obese, and particularly amongst normal weight subjects, is not known and is a priority for further investigation.

  17. Sun Exposure and Its Effects on Human Health: Mechanisms through Which Sun Exposure Could Reduce the Risk of Developing Obesity and Cardiometabolic Dysfunction

    Science.gov (United States)

    Fleury, Naomi; Geldenhuys, Sian; Gorman, Shelley

    2016-01-01

    Obesity is a significant burden on global healthcare due to its high prevalence and associations with chronic health conditions. In our animal studies, ongoing exposure to low dose ultraviolet radiation (UVR, found in sunlight) reduced weight gain and the development of signs of cardiometabolic dysfunction in mice fed a high fat diet. These observations suggest that regular exposure to safe levels of sunlight could be an effective means of reducing the burden of obesity. However, there is limited knowledge around the nature of associations between sun exposure and the development of obesity and cardiometabolic dysfunction, and we do not know if sun exposure (independent of outdoor activity) affects the metabolic processes that determine obesity in humans. In addition, excessive sun exposure has strong associations with a number of negative health consequences such as skin cancer. This means it is very important to “get the balance right” to ensure that we receive benefits without increasing harm. In this review, we detail the evidence around the cardiometabolic protective effects of UVR and suggest mechanistic pathways through which UVR could be beneficial. PMID:27727191

  18. Gastric emptying of solids in humans: improved evaluation by Kaplan-Meier plots, with special reference to obesity and gender

    International Nuclear Information System (INIS)

    Grybaeck, P.; Naeslund, E.; Hellstroem, P.M.; Jacobsson, H.; Backman, L.

    1996-01-01

    It has been suggested that obesity is associated with an altered rate of gastric emptying, and that there are also sex differences in gastric emptying. The results of earlier studies examining gastric emptying rates in obesity and in males and females have proved inconsistent. The aim of this study was to investigate the influence of obesity and gender on gastric emptying, by extending conventional evaluation methods with Kaplan-Meier plots, in order to assess whether these factors have to be accounted for when interpreting results of scintigraphic gastric emptying tests. Twenty-one normal-weight volunteers and nine obese subjects were fed a standardised technetium-99m labelled albumin omelette. Imaging data were acquired at 5- and 10-min intervals in both posterior and anterior projections with the subjects in the sitting position. The half-emptying time, analysed by Kaplan-Meier plot (log-rank test), were shorter in obese subjects compared to normal-weight subjects and later in females compared to males. Also, the lag-phase and half-emptying time were shorter in obese females than in normal females. This study shows an association between different gastric emptying rates and obesity and gender. Therefore, body mass index and gender have to be accounted for when interpreting results of scintigraphic gastric emptying studies. (orig.). With 6 figs., 4 tabs

  19. Gastric emptying of solids in humans: improved evaluation by Kaplan-Meier plots, with special reference to obesity and gender

    Energy Technology Data Exchange (ETDEWEB)

    Grybaeck, P. [Department of Diagnostic Radiology, Karolinska Hospital, Stockholm (Sweden); Naeslund, E. [Department of Surgery, Karolinska Institute at Danderyd Hospital, Stockholm (Sweden); Hellstroem, P.M. [Department of Internal Medicine, Karolinska Hospital, Stockholm (Sweden); Jacobsson, H. [Department of Diagnostic Radiology, Karolinska Hospital, Stockholm (Sweden)]|[Department of Nuclear Medicine, Karolinska Hospital, Stockholm (Sweden); Backman, L. [Department of Surgery, Karolinska Institute at Danderyd Hospital, Stockholm (Sweden)

    1996-12-01

    It has been suggested that obesity is associated with an altered rate of gastric emptying, and that there are also sex differences in gastric emptying. The results of earlier studies examining gastric emptying rates in obesity and in males and females have proved inconsistent. The aim of this study was to investigate the influence of obesity and gender on gastric emptying, by extending conventional evaluation methods with Kaplan-Meier plots, in order to assess whether these factors have to be accounted for when interpreting results of scintigraphic gastric emptying tests. Twenty-one normal-weight volunteers and nine obese subjects were fed a standardised technetium-99m labelled albumin omelette. Imaging data were acquired at 5- and 10-min intervals in both posterior and anterior projections with the subjects in the sitting position. The half-emptying time, analysed by Kaplan-Meier plot (log-rank test), were shorter in obese subjects compared to normal-weight subjects and later in females compared to males. Also, the lag-phase and half-emptying time were shorter in obese females than in normal females. This study shows an association between different gastric emptying rates and obesity and gender. Therefore, body mass index and gender have to be accounted for when interpreting results of scintigraphic gastric emptying studies. (orig.). With 6 figs., 4 tabs.

  20. Personalized nutrition and obesity.

    Science.gov (United States)

    Qi, Lu

    2014-08-01

    The past few decades have witnessed a rapid rise in nutrition-related disorders such as obesity in the United States and over the world. Traditional nutrition research has associated various foods and nutrients with obesity. Recent advances in genomics have led to identification of the genetic variants determining body weight and related dietary factors such as intakes of energy and macronutrients. In addition, compelling evidence has lent support to interactions between genetic variations and dietary factors in relation to obesity and weight change. Moreover, recently emerging data from other 'omics' studies such as epigenomics and metabolomics suggest that more complex interplays between the global features of human body and dietary factors may exist at multiple tiers in affecting individuals' susceptibility to obesity; and a concept of 'personalized nutrition' has been proposed to integrate this novel knowledge with traditional nutrition research, with the hope ultimately to endorse person-centric diet intervention to mitigate obesity and related disorders.

  1. Nanotechnology in elevation of the worldwide impact of obesity and obesity-related diseases: potential roles in human health and disease.

    Science.gov (United States)

    Eldaw, Abdellatif

    2011-07-01

    Current worldwide data show epidemics of obesity and type 2 diabetes with no real solutions apart from continuous calls to changing lifestyle and food habits. Despite health messages that are communicated by health authorities, the epidemic is growing. More people are affected with health consequences that are usually frightening as more resources are wasted, especially in areas where health care and resources are lacking. Nanotechnology applications in food industry present practical approaches that help produce more tasty food with little calories, functional foods, and nutritional supplements and alter the fats and sugar contents of our foods with potential for many more applications. Consequently, this opens more windows to better control of many nutritional deficiencies as well as obesity and type 2 diabetes, especially among children and young adults who are addicted to fast food. With such potential, food producers, policy makers, health authorities, food scientists, and governments need to collaborate and make all possible efforts to fund and support research in different areas of food produced using nanotechnology. So far, consumers are not prepared to accept food produced using nanotechnology, mainly because information on the safety of such products are not enough. This issue needs to be addressed and researched well using suitable risk assessment methodologies. Consumers need to be assured, and involved as well, to avoid the "refusal state" that still exists against many safe products such as genetically modified organisms and irradiated food. There is the possibility that consumers could perceive that they will bear the potential risks posed by nanotechnology applications while the benefits will accrue mainly to others, such as food processors or farmers. © 2011 Diabetes Technology Society.

  2. Growth hormone signaling in muscle and adipose tissue of obese human subjects: associations with measures of body composition and interaction with resveratrol treatment.

    Science.gov (United States)

    Clasen, Berthil F; Poulsen, Morten M; Escande, Carlos; Pedersen, Steen B; Møller, Niels; Chini, Eduardo N; Jessen, Niels; Jørgensen, Jens O L

    2014-12-01

    Growth hormone (GH) secretion is reduced in obesity, despite normal serum insulin-like growth factor I (IGF-1) levels, but the association between obesity and the GH signaling is unknown. Furthermore, SIRT1, an nicotinamide adenine dinucleotide-dependent protein deacetylase, reduces hepatic IGF-1 production in mice via blunting of GH-induced STAT5 signaling. To study GH signaling in muscle and fat in obese subjects and the interaction with concomitant administration of the putative SIRT1 activator resveratrol, and to assess the effects of inhibiting or knocking down SIRT1 on GH regulated genes in vitro. Twenty-four obese males were examined in a randomized, double blinded, parallel-group study with resveratrol or placebo treatment for 5 weeks followed by a GH bolus. Muscle and fat biopsies were collected before and after GH. Body composition was assessed by DEXA and MRI. (1) Effect of body composition and age on GH-stimulated STAT5b phosphorylation and IGF-1, SOCS2, and CISH mRNA in muscle and fat. (2) The impact of resveratrol treatment on GH activity. (3) Impact of inhibiting or knocking down SIRT1 on effects of GH in vitro. Significant GH-induced STAT5b phosphorylation in muscle and fat in obese subjects was recorded together with increased CISH and SOCS2 mRNA. GH-induced STAT5b phosphorylation in muscle correlated positively with age [r = 0.53, p body composition. Resveratrol administration had no impact on body composition, serum IGF-1, or GH signaling in vivo, and SIRT1 knock down or inhibition did not affect GH signaling in vitro. (1) GH induced STAT5b phosphorylation is detectable in muscle and fat in adult males with simple obesity, but is not determined by body composition. (2) Resveratrol supplementation does not impact circulating IGF-1 levels or GH signaling in human muscle and fat. (3) Our data speak against a major impact of SIRT1on GH action in human subjects.

  3. Genome-wide association study reveals genetic architecture of eating behavior in pigs and its implications for humans obesity by comparative mapping

    DEFF Research Database (Denmark)

    Do, Duy Ngoc; Strathe, Anders Bjerring; Ostersen, Tage

    2013-01-01

    This study was aimed at identifying genomic regions controlling feeding behavior in Danish Duroc boars and its potential implications for eating behavior in humans. Data regarding individual daily feed intake (DFI), total daily time spent in feeder (TPD), number of daily visits to feeder (NVD......1, PTPN4, MTMR4 and RNGTT) and positive regulation of peptide secretion genes (GHRH, NNAT and TCF7L2) were highly significantly associated with feeding behavior traits. This is the first GWAS to identify genetic variants and biological mechanisms for eating behavior in pigs and these results...... are important for genetic improvement of pig feed efficiency. We have also conducted pig-human comparative gene mapping to reveal key genomic regions and/or genes on the human genome that may influence eating behavior in human beings and consequently affect the development of obesity and metabolic syndrome...

  4. Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.

    Science.gov (United States)

    Tamboli, Robyn A; Antoun, Joseph; Sidani, Reem M; Clements, Austin; Harmata, Emily E; Marks-Shulman, Pam; Gaylinn, Bruce D; Williams, Brandon; Clements, Ronald H; Albaugh, Vance L; Abumrad, Naji N

    2017-09-01

    Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg -1  min -1 ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp. Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion. These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB. © 2017 John Wiley & Sons Ltd.

  5. Obesity or Overweight, a Chronic Inflammatory Status in Male Reproductive System, Leads to Mice and Human Subfertility

    Directory of Open Access Journals (Sweden)

    Weimin Fan

    2018-01-01

    Full Text Available Obesity is frequently accompanied with chronic inflammation over the whole body and is always associated with symptoms that include those arising from metabolic and vascular alterations. On the other hand, the chronic inflammatory status in the male genital tract may directly impair spermatogenesis and is even associated with male subfertility. However, it is still unclear if the chronic inflammation induced by obesity damages spermatogenesis in the male genital tract. To address this question, we used a high fat diet (HFD induced obese mouse model and recruited obese patients from the clinic. We detected increased levels of tumor necrosis factor (TNF-α, interleukin-6 (IL-6, and NOD-like receptor family pyrin domain containing-3 (NLRP3 in genital tract tissues including testis, epididymis, seminal vesicle, prostate, and serum from obese mice. Meanwhile, the levels of immunoglobulin G (IgG and corticosterone were significantly higher than those in the control group in serum. Moreover, signal factors regulated by TNF-α, i.e., p38, nuclear factor-κB (NF-κB, Jun N-terminal kinase (JNK, extracellular signal-regulated kinase (ERK, and their phosphorylated status, and inflammasome protein NLRP3 were expressed at higher levels in the testis. For overweight and obese male patients, the increased levels of TNF-α and IL-6 were also observed in their seminal plasma. Furthermore, there was a positive correlation between the TNF-α and IL-6 levels and BMI whereas they were inversely correlated with the sperm concentration and motility. In conclusion, impairment of male fertility may stem from a chronic inflammatory status in the male genital tract of obese individuals.

  6. Effects of Probiotics and Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Review of Human Clinical Trials.

    Science.gov (United States)

    Sáez-Lara, Maria Jose; Robles-Sanchez, Candido; Ruiz-Ojeda, Francisco Javier; Plaza-Diaz, Julio; Gil, Angel

    2016-06-13

    The use of probiotics and synbiotics in the prevention and treatment of different disorders has dramatically increased over the last decade. Both probiotics and synbiotics are well known ingredients of functional foods and nutraceuticals and may provide beneficial health effects because they can influence the intestinal microbial ecology and immunity. The present study reviews the effects of probiotics and synbiotics on obesity, insulin resistance syndrome (IRS), type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) in human randomized clinical trials. Select probiotics and synbiotics provided beneficial effects in patients with obesity, mainly affecting the body mass index and fat mass. Some probiotics had beneficial effects on IRS, decreasing the cell adhesion molecule-1 levels, and the synbiotics decreased the insulin resistance and plasma lipid levels. Moreover, select probiotics improved the carbohydrate metabolism, fasting blood glucose, insulin sensitivity and antioxidant status and also reduced metabolic stress in subjects with T2D. Some probiotics and synbiotics improved the liver and metabolic parameters in patients with NAFLD. The oral intake of probiotics and synbiotics as co-adjuvants for the prevention and treatment of obesity, IRS, T2D and NAFLD is partially supported by the data shown in the present review. However, further studies are required to understand the precise mechanism of how probiotics and synbiotics affect these metabolic disorders.

  7. Effects of Probiotics and Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Review of Human Clinical Trials

    Directory of Open Access Journals (Sweden)

    Maria Jose Sáez-Lara

    2016-06-01

    Full Text Available The use of probiotics and synbiotics in the prevention and treatment of different disorders has dramatically increased over the last decade. Both probiotics and synbiotics are well known ingredients of functional foods and nutraceuticals and may provide beneficial health effects because they can influence the intestinal microbial ecology and immunity. The present study reviews the effects of probiotics and synbiotics on obesity, insulin resistance syndrome (IRS, type 2 diabetes (T2D and non-alcoholic fatty liver disease (NAFLD in human randomized clinical trials. Select probiotics and synbiotics provided beneficial effects in patients with obesity, mainly affecting the body mass index and fat mass. Some probiotics had beneficial effects on IRS, decreasing the cell adhesion molecule-1 levels, and the synbiotics decreased the insulin resistance and plasma lipid levels. Moreover, select probiotics improved the carbohydrate metabolism, fasting blood glucose, insulin sensitivity and antioxidant status and also reduced metabolic stress in subjects with T2D. Some probiotics and synbiotics improved the liver and metabolic parameters in patients with NAFLD. The oral intake of probiotics and synbiotics as co-adjuvants for the prevention and treatment of obesity, IRS, T2D and NAFLD is partially supported by the data shown in the present review. However, further studies are required to understand the precise mechanism of how probiotics and synbiotics affect these metabolic disorders.

  8. Childhood Obesity

    Science.gov (United States)

    Yuca, Sevil Ari, Ed.

    2012-01-01

    This book aims to provide readers with a general as well as an advanced overview of the key trends in childhood obesity. Obesity is an illness that occurs due to a combination of genetic, environmental, psychosocial, metabolic and hormonal factors. The prevalence of obesity has shown a great rise both in adults and children in the last 30 years.…

  9. GLP-1 and Calcitonin Concentration in Humans: Lack of Evidence of Calcitonin Release from Sequential Screening in over 5000 Subjects with Type 2 Diabetes or Nondiabetic Obese Subjects Treated with the Human GLP-1 Analog, Liraglutide

    DEFF Research Database (Denmark)

    Hegedüs, Laszlo; Moses, Alan C; Zdravkovic, Milan

    2011-01-01

    to the GLP-1 receptor agonist liraglutide in subjects with type 2 diabetes mellitus or nondiabetic obese subjects. Methods: Unstimulated serum CT concentrations were measured at 3-month intervals for no more than 2 yr in a series of trials in over 5000 subjects receiving liraglutide or control therapy....... There are no longitudinal studies measuring CT in humans without medullary thyroid carcinoma or a family history of medullary thyroid carcinoma and no published studies on the effect of GLP-1 receptor agonists on human serum CT concentrations. Aim: The aim of the study was to determine serum CT response over time...

  10. Superparamagnetic iron oxide nanoparticles alter expression of obesity and T2D-associated risk genes in human adipocytes

    NARCIS (Netherlands)

    Sharifi, S.; Daghighi, S.; Motazacker, M. M.; Badlou, B.; Sanjabi, B.; Akbarkhanzadeh, A.; Rowshani, A. T.; Laurent, S.; Peppelenbosch, M. P.; Rezaee, F.

    2013-01-01

    Adipocytes hypertrophy is the main cause of obesity and its affliction such as type 2 diabetes (T2D). Since superparamagnetic iron oxide nanoparticles (SPIONs) are used for a wide range of biomedical/medical applications, we aimed to study the effect of SPIONs on 22 and 29 risk genes (Based on gene

  11. Do nutrient-gut-microbiota interactions play a role in human obesity, insulin resistance and type 2 diabetes?

    NARCIS (Netherlands)

    Diamant, M.; Blaak, E.E; Vos, W.M.

    2011-01-01

    The current obesity and type 2 diabetes pandemics have causes beyond changes in eating and exercise habits against a susceptible genetic background. Gut bacteria seem to additionally contribute to the differences in body weight, fat distribution, insulin sensitivity and glucose- and

  12. Modulation of natriuretic peptide receptors in human adipose tissue: molecular mechanisms behind the "natriuretic handicap" in morbidly obese patients.

    Science.gov (United States)

    Gentili, Alessandra; Frangione, Maria Rosaria; Albini, Elisa; Vacca, Carmine; Ricci, Maria Anastasia; De Vuono, Stefano; Boni, Marcello; Rondelli, Fabio; Rotelli, Luciana; Lupattelli, Graziana; Orabona, Ciriana

    2017-08-01

    The B-type natriuretic peptide (BNP) hormone plays a crucial role in the regulation of cardiovascular and energy homeostasis. Obesity is associated with low circulating levels of BNP, a condition known as "natriuretic handicap." Recent evidences suggest an altered expression of BNP receptors-both the signaling natriuretic peptide receptors (NPR)-A and the clearance NPR-C receptor-in adipose tissue (AT) as one of the putative causes of natriuretic handicap. The current study aims at clarifying the molecular mechanisms behind the natriuretic handicap, focusing on NPR modulation in the AT of obese and control subjects. The study enrolled 34 obese and 20 control subjects undergoing bariatric or abdominal surgery, respectively. The main clinical and biochemical parameters, including circulating BNP, were assessed. In visceral (VAT) and subcutaneous AT (SAT) samples, collected during surgery, the adipocytes and stromal vascular fraction (SVF) expression of NPR-A and NPR-C and the SVF secretion of interleukin 6 (IL-6) were determined. Both VAT and SAT from obese patients expressed a lower NPR-A/NPR-C ratio in adipocytes and the SVF secreted a higher level of IL-6, compared with the controls. Moreover, NPR-A/NPR-C ratio expressed by VAT and SAT adipocytes negatively correlated with body mass index, insulin, the Homeostasis Model Assessment of Insulin resistance, and IL-6 secreted by SVF, and the expression of the clearance receptor NPR-C, in both the VAT and SAT adipocytes, showed a negative correlation with circulating BNP. Overall, insulin resistance/hyperinsulinemia and AT inflammation (ie, high level of IL-6) are the major determinants of the lower NPR-A/NPR-C ratio in adipocytes, thus contributing to the natriuretic handicap in obese subjects. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Characterization of stromal vascular fraction and adipose stem cells from subcutaneous, preperitoneal and visceral morbidly obese human adipose tissue depots.

    Science.gov (United States)

    Silva, Karina Ribeiro; Côrtes, Isis; Liechocki, Sally; Carneiro, João Regis Ivar; Souza, Antônio Augusto Peixoto; Borojevic, Radovan; Maya-Monteiro, Clarissa Menezes; Baptista, Leandra Santos

    2017-01-01

    The pathological condition of obesity is accompanied by a dysfunctional adipose tissue. We postulate that subcutaneous, preperitoneal and visceral obese abdominal white adipose tissue depots could have stromal vascular fractions (SVF) with distinct composition and adipose stem cells (ASC) that would differentially account for the pathogenesis of obesity. In order to evaluate the distribution of SVF subpopulations, samples of subcutaneous, preperitoneal and visceral adipose tissues from morbidly obese women (n = 12, BMI: 46.2±5.1 kg/m2) were collected during bariatric surgery, enzymatically digested and analyzed by flow cytometry (n = 12). ASC from all depots were evaluated for morphology, surface expression, ability to accumulate lipid after induction and cytokine secretion (n = 3). A high content of preadipocytes was found in the SVF of subcutaneous depot (p = 0.0178). ASC from the three depots had similar fibroblastoid morphology with a homogeneous expression of CD34, CD146, CD105, CD73 and CD90. ASC from the visceral depot secreted the highest levels of IL-6, MCP-1 and G-CSF (p = 0.0278). Interestingly, preperitoneal ASC under lipid accumulation stimulus showed the lowest levels of all the secreted cytokines, except for adiponectin that was enhanced (p = 0.0278). ASC from preperitoneal adipose tissue revealed the less pro-inflammatory properties, although it is an internal adipose depot. Conversely, ASC from visceral adipose tissue are the most pro-inflammatory. Therefore, ASC from subcutaneous, visceral and preperitoneal adipose depots could differentially contribute to the chronic inflammatory scenario of obesity.

  14. Interactions between Obesity Status and Dietary Intake of Monounsaturated and Polyunsaturated Oils on Human Gut Microbiome Profiles in the Canola Oil Multicenter Intervention Trial (COMIT

    Directory of Open Access Journals (Sweden)

    Shuaihua Pu

    2016-10-01

    Full Text Available Long-term dietary fatty acid intake is believed to induce changes in the human gut microbiome which might be associated with human health or obesity status; however, considerable debate remains regarding the most favorable ratios of fatty acids to optimize these processes. The objective of this sub-study of a double-blinded randomized crossover clinical study, the canola oil multi-center intervention trial (COMIT, was to investigate effects of five different novel oil blends fed for 30 days each on the intestinal microbiota in 25 volunteers with risk of metabolic syndrome. The 60 g treatments included three MUFA-rich diets: 1 conventional canola oil (Canola; 2 DHA-enriched high oleic canola oil (CanolaDHA; 3 high oleic canola oil (CanolaOleic; and two PUFA-rich diets: 4 a blend of corn/safflower oil (25:75 (CornSaff; and 5 a blend of flax/safflower oil (60:40 (FlaxSaff. Stool samples were collected at the end of each period. DNA was extracted and amplified for pyrosequencing. A total of 17 phyla and 187 genera were identified. While five novel oil treatments failed to alter bacterial phyla composition, obese participants produced a higher proportion of Firmicutes to Bacteroidetes than overweight or normal weight groups (P = 0.01. Similarly at the genus level, overall bacterial distribution was highly associated with subjects’ body mass index (BMI. Treatment effects were observed between MUFA- and PUFA-rich diets, with the three MUFA diets elevating Parabacteroides, Prevotella, Turicibacter, and Enterobacteriaceae (F’s populations, while the two PUFA-rich diets favored the abundance of Isobaculum. High MUFA content feedings also resulted in an increase of Parabacteroides and a decrease of Isobaculum in obese, but not overweight subjects. Data suggest that BMI is a predominant factor in characterization of human gut microbiota profiles, and that MUFA-rich and PUFA-rich diets impact the composition of gut microbiota at lower taxonomical levels

  15. The biological control of voluntary exercise, spontaneous physical activity and daily energy expenditure in relation to obesity: human and rodent perspectives.

    Science.gov (United States)

    Garland, Theodore; Schutz, Heidi; Chappell, Mark A; Keeney, Brooke K; Meek, Thomas H; Copes, Lynn E; Acosta, Wendy; Drenowatz, Clemens; Maciel, Robert C; van Dijk, Gertjan; Kotz, Catherine M; Eisenmann, Joey C

    2011-01-15

    Mammals expend energy in many ways, including basic cellular maintenance and repair, digestion, thermoregulation, locomotion, growth and reproduction. These processes can vary tremendously among species and individuals, potentially leading to large variation in daily energy expenditure (DEE). Locomotor energy costs can be substantial for large-bodied species and those with high-activity lifestyles. For humans in industrialized societies, locomotion necessary for daily activities is often relatively low, so it has been presumed that activity energy expenditure and DEE are lower than in our ancestors. Whether this is true and has contributed to a rise in obesity is controversial. In humans, much attention has centered on spontaneous physical activity (SPA) or non-exercise activity thermogenesis (NEAT), the latter sometimes defined so broadly as to include all energy expended due to activity, exclusive of volitional exercise. Given that most people in Western societies engage in little voluntary exercise, increasing NEAT may be an effective way to maintain DEE and combat overweight and obesity. One way to promote NEAT is to decrease the amount of time spent on sedentary behaviours (e.g. watching television). The effects of voluntary exercise on other components of physical activity are highly variable in humans, partly as a function of age, and have rarely been studied in rodents. However, most rodent studies indicate that food consumption increases in the presence of wheels; therefore, other aspects of physical activity are not reduced enough to compensate for the energetic cost of wheel running. Most rodent studies also show negative effects of wheel access on body fat, especially in males. Sedentary behaviours per se have not been studied in rodents in relation to obesity. Several lines of evidence demonstrate the important role of dopamine, in addition to other neural signaling networks (e.g. the endocannabinoid system), in the control of voluntary exercise. A

  16. Robust anti-obesity and metabolic effects of a dual GLP-1/glucagon receptor peptide agonist in rodents and non-human primates.

    Science.gov (United States)

    Henderson, S J; Konkar, A; Hornigold, D C; Trevaskis, J L; Jackson, R; Fritsch Fredin, M; Jansson-Löfmark, R; Naylor, J; Rossi, A; Bednarek, M A; Bhagroo, N; Salari, H; Will, S; Oldham, S; Hansen, G; Feigh, M; Klein, T; Grimsby, J; Maguire, S; Jermutus, L; Rondinone, C M; Coghlan, M P

    2016-12-01

    To characterize the pharmacology of MEDI0382, a peptide dual agonist of glucagon-like peptide-1 (GLP-1) and glucagon receptors. MEDI0382 was evaluated in vitro for its ability to stimulate cAMP accumulation in cell lines expressing transfected recombinant or endogenous GLP-1 or glucagon receptors, to potentiate glucose-stimulated insulin secretion (GSIS) in pancreatic β-cell lines and stimulate hepatic glucose output (HGO) by primary hepatocytes. The ability of MEDI0382 to reduce body weight and improve energy balance (i.e. food intake and energy expenditure), as well as control blood glucose, was evaluated in mouse models of obesity and healthy cynomolgus monkeys following single and repeated daily subcutaneous administration for up to 2 months. MEDI0382 potently activated rodent, cynomolgus and human GLP-1 and glucagon receptors and exhibited a fivefold bias for activation of GLP-1 receptor versus the glucagon receptor. MEDI0382 produced superior weight loss and comparable glucose lowering to the GLP-1 peptide analogue liraglutide when administered daily at comparable doses in DIO mice. The additional fat mass reduction elicited by MEDI0382 probably results from a glucagon receptor-mediated increase in energy expenditure, whereas food intake suppression results from activation of the GLP-1 receptor. Notably, the significant weight loss elicited by MEDI0382 in DIO mice was recapitulated in cynomolgus monkeys. Repeated administration of MEDI0382 elicits profound weight loss in DIO mice and non-human primates, produces robust glucose control and reduces hepatic fat content and fasting insulin and glucose levels. The balance of activities at the GLP-1 and glucagon receptors is considered to be optimal for achieving weight and glucose control in overweight or obese Type 2 diabetic patients. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  17. Obesity Prevalence Maps

    Science.gov (United States)

    ... Obesity Causes & Consequences CDC Reports Improvement in Childhood Obesity among Young Children Participating in WIC Data & Statistics Adult Obesity Facts Childhood Obesity Facts Data, Trends and ...

  18. Phthalate exposure and childhood obesity

    Directory of Open Access Journals (Sweden)

    Shin Hye Kim

    2014-06-01

    Full Text Available Phthalates are commonly used as plasticizers and vehicles for cosmetic ingredients. Phthalate metabolites have documented biochemical activity including activating peroxisome proliferator-activated receptor and antiandrogenic effects, which may contribute to the development of obesity. In vitro and in vivo studies suggest that phthalates have significant effects on the development of obesity, especially after prenatal exposure at low doses. Although few studies have examined the effects of phthalate on obesity development in humans, some work has shown that phthalates affect humans and animals similarly. In this paper, we review the possible mechanisms of phthalate-induced obesity, and discuss evidence supporting the role of phthalates in the development of obesity in humans.

  19. Investigations of the human endocannabinoid system in two subcutaneous adipose tissue depots in lean subjects and in obese subjects before and after weight loss

    DEFF Research Database (Denmark)

    Bennetzen, Marianne Faurholt; Wellner, Niels; Ahmed, Syed Sayeem Uddin

    2011-01-01

    Endocannabinoids (ECs) have a role in obesity by affecting appetite and through peripheral effects. Obesity is associated with a dysregulation of the endocannabinoid system (ECS).......Endocannabinoids (ECs) have a role in obesity by affecting appetite and through peripheral effects. Obesity is associated with a dysregulation of the endocannabinoid system (ECS)....

  20. Relationship of tumor necrosis factor alpha genotypes with various biochemical parameters of normal, over weight and obese human subjects

    International Nuclear Information System (INIS)

    Raza, M.; Chaudhary, B.; Shakoori, A.R.

    2008-01-01

    Tumor Necrosis Factor (TNF-alpha) is expressed primarily in adipocytes and elevated levels of this cytokine have been associated with obesity. The purpose of this investigation was to test whether the TNF-alpha -308 polymorphism were associated with insulin resistance or obesity related traits in non-diabetic and diabetic patients visiting Sheikh Zayed Hospital, Lahore, Fatima Hospital and Irfan Clinic in Sargodha. In non diabetic subjects the AA allele carriers, compared with homozygous G allele carriers had significantly lower (28%) triglyceride values and 15% higher HDL yal ues, whereas other parameters tested 81id not show any significant variation. In diabetic patients the AA allele carriers, compared with GG allele carriers, besides having 31 % higher FBS and 26% higher creatinine, had 20% higher cholesterol and 34% higher triglycerides. The HDL values were 14% less, compared to GG allele carriers. In normal subjects (BMI 22.85:1:0.25 kgim2), the AA allele carriers showed 132%, 125%, 65% and 112% higher triglycerides, cholesterol and LDL values compared with GG allele carriers. The HDL and creatinine did not show any significant change. In the overweight subjects (BMI: 27.17+-0.17 kgim/sup 2/) all these values were lower than in AA allele carriers compared with GG allele carriers. The AA allele carries had FBS, triglycerides, cholesterol and LDL 28%, 48%, 14% and 14% lower than in the GG allele' carriers, respectively. In obese subjects, (BMI: 36.73+-0.78kgm/sup 2/), however, the FBS, triglycerides, cholesterol and creatinine values were 5%, 8%, 7% and 14% higher in AA allele carries compared to GG allele carriers, respectively. The LDL content was 8% lower in AA allele carrier as compared with the respective GG allele carriers, It is concluded that replacement of G at -308 with A leads to reduced risk for cardiovascular disease in non-diabetic subject, whereas in diabetic patients this mutation-increases the risk of CVD. Using BMI as index of obesity, it was

  1. Latest data on obesity

    Directory of Open Access Journals (Sweden)

    Evangelos Fousteris

    2017-01-01

    Full Text Available Obesity is a chronic and morbid disease which has reached epidemic dimensions nowadays, becoming the springboard for the emergence of other unfavorable metabolic diseases such as type 2 diabetes mellitus. In 2014 overweight and obese people in the world were estimated at 2.022 billion while prediction for 2025 is to reach 2.693 billion. Regarding the statistical data from Greece, we should note that overweight and obese individuals are estimated at 5.266 million for 2014. Obesity is a systemic disease with significant impact on human health, such as increased incidence of type 2 diabetes, osteoarthritis ( knee, hip, cancers (mostly breast and endometrium for women and colon and kidney for men, cognitive disorders (dementia, Alzheimer's, mood disorders (anxiety, depression, emotional eating disorders, sleep apnea syndrome, cardiovascular disease (myocardial infarction, stroke and increased incidence of all-cause mortality, reducing in this patern the overall life expectancy. The underlying pathophysiological disorders of obesity are complex and mostly not understood well. The main disorder is the disturbance of the human energy balance when intake calories are more than the calories consumed, thus an excess of energy is generated daily, which is stored by the body in the form of triglycerides in adipose tissue of the body. On the other hand, weight loss is very important since even moderate weight loss significantly reduces the comorbidities of obesity. For the treatment of obesity, we have dietary interventions (hypocaloric diets, very low calorie diets, special diets, exercise interventions, pharmacological interventions (Orlistat, Liraglutide, Naltrexone / Boupropion, Phentermine / Topiramate, Lorcaserin and bariatric surgery (gastric banding, gastric Roux-en-Y by pass, sleeve gastrectomy. Despite all these, obesity remains an unsolved problem of our time with unmet needs that need combined global awareness from both the scientific community

  2. Preadipocytes from obese humans with type 2 diabetes are epigenetically reprogrammed at genes controlling adipose tissue function

    DEFF Research Database (Denmark)

    Andersen, Emil; Ingerslev, Lars Roed; Fabre, Odile

    2018-01-01

    BACKGROUND: Deterioration of the adipogenic potential of preadipocytes may contribute to adipose tissue dysfunction in obesity and type 2 diabetes (T2D). Here, we hypothesized that extracellular factors in obesity epigenetically reprogram adipogenesis potential and metabolic function...... and CD36) were associated with DNA methylation remodelling at genes controlling insulin sensitivity and adipocytokine signalling pathways. Prior incubation of 3T3-L1 preadipocytes with TNF-α or palmitate markedly altered insulin responsiveness and metabolic function in the differentiated adipocytes......, and remodelled DNA methylation and gene expression at specific genes, notably related to PPAR signalling. CONCLUSIONS: Our findings that preadipocytes retain the memory of the donor in culture and can be reprogrammed by extracellular factors support a mechanism by which adipocyte precursors are epigenetically...

  3. Childhood obesity.

    Science.gov (United States)

    Reinehr, Thomas; Wabitsch, Martin

    2011-02-01

    As childhood obesity is associated with premature death in adults, a research is critical. This review focuses on the recent proceedings concerning genesis, prevention, and treatment. Identifying genetic variants in well phenotyped small cohorts of extremely obese children (e.g., the search for copy number variants in obesity-associated large chromosomal deletions) confirmed afterwards in large population-based studies is a new promising genetic approach to understand the disposition to obesity. A further important finding is that obesity of mothers predisposes their offsprings to obesity by epigenetic, prenatal effects. Therefore, prevention programs targeting parents even before pregnancy should be developed. Prevention programs in kindergarten and schools without involving the parents failed to fight against the obesity epidemic. A new promising prevention approach is to change the environment (e.g., ban on sugar drinks in schools). Therapy of choice in already obese children is lifestyle intervention. Again, including their parents is crucial for success. However, this kind of intervention is only suitable for families motivated to change their lifestyle habits. Especially in extremely obese adolescents, additional therapeutic approaches such as drugs and bariatric surgery have to be considered. Even if of knowledge of childhood obesity improves every year, many questions concerning prevention and treatment remain still open. Future longitudinal research has to focus on which children will benefit from which kind of intervention to develop specific therapies.

  4. The influence of obesity on the effects of spirulina supplementation in the human metabolic response of Korean elderly

    OpenAIRE

    Park, Hee-Jung; Lee, Hyun-Sook

    2016-01-01

    BACKGROUND/OBJECTIVES Spirulina, a blue-green alga, is widely produced and commercialized as a dietary supplement with bio- and immune-modulatory functions. We have previously shown that spirulina had favorable effects on lipid profiles, immune functions, and antioxidant capacity in healthy Korean elderly. Despite favorable effect of spirulina supplementation, some sub-populations have shown a poor response to supplementation. Obesity is a factor related to poor-response. Therefore, the purpo...

  5. Proteomics reveals changes in hepatic proteins during chicken embryonic development: an alternative model to study human obesity

    OpenAIRE

    Peng, Mengling; Li, Shengnan; He, Qianian; Zhao, Jinlong; Li, Longlong; Ma, Haitian

    2018-01-01

    Background Chicken embryos are widely used as a model for studies of obesity; however, no detailed information is available about the dynamic changes of proteins during the regulation of adipose biology and metabolism. Thus, the present study used an isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic approach to identify the changes in protein abundance at different stages of chicken embryonic development. Results In this study, the abundances of 293 hepatic proteins...

  6. Human-specific SNP in obesity genes, adrenergic receptor beta2 (ADRB2, Beta3 (ADRB3, and PPAR γ2 (PPARG, during primate evolution.

    Directory of Open Access Journals (Sweden)

    Akiko Takenaka

    Full Text Available UNLABELLED: Adrenergic-receptor beta2 (ADRB2 and beta3 (ADRB3 are obesity genes that play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. The Glu27 allele in ADRB2 and the Arg64 allele in ADRB3 are associated with abdominal obesity and early onset of non-insulin-dependent diabetes mellitus (NIDDM in many ethnic groups. Peroxisome proliferator-activated receptor γ (PPARG is required for adipocyte differentiation. Pro12Ala mutation decreases PPARG activity and resistance to NIDDM. In humans, energy-expense alleles, Gln27 in ADRB2 and Trp64 in ADRB3, are at higher frequencies than Glu27 and Arg64, respectively, but Ala12 in PPARG is at lower frequency than Pro12. Adaptation of humans for lipolysis, thermogenesis, and reduction of fat accumulation could be considered by examining which alleles in these genes are dominant in non-human primates (NHP. All NHP (P. troglodytes, G. gorilla, P. pygmaeus, H. agilis and macaques had energy-thrifty alleles, Gly16 and Glu27 in ADRB2, and Arg64 in ADRB3, but did not have energy-expense alleles, Arg16, Gln27 and Trp64 alleles. In PPARG gene, all NHP had large adipocyte accumulating type, the Pro12 allele. CONCLUSIONS: These results indicate that a tendency to produce much more heat through the energy-expense alleles developed only in humans, who left tropical rainforests for savanna and developed new features in their heat-regulation systems, such as reduction of body hair and increased evaporation of water, and might have helped the protection of entrails from cold at night, especially in glacial periods.

  7. Obesity vaccines

    OpenAIRE

    Monteiro, Mariana P

    2013-01-01

    Obesity is one of the largest and fastest growing public health problems in the world. Last century social changes have set an obesogenic milieu that calls for micro and macro environment interventions for disease prevention, while treatment is mandatory for individuals already obese. The cornerstone of overweight and obesity treatment is diet and physical exercise. However, many patients find lifestyle modifications difficult to comply and prone to failure in the long-term; therefore many pa...

  8. Butyricimonas phoceensis sp. nov., a new anaerobic species isolated from the human gut microbiota of a French morbidly obese patient.

    Science.gov (United States)

    Togo, A H; Diop, A; Dubourg, G; Nguyen, T T; Andrieu, C; Caputo, A; Couderc, C; Fournier, P-E; Maraninchi, M; Valero, R; Raoult, D; Million, M

    2016-11-01

    Butyricimonas phoceensis strain AT9 (= CSUR 1981 = DSM 100664) was isolated from a stool sample from a morbidly obese French patient living in Marseille using the culturomics approach. The genome of this Gram-negative-staining, anaerobic and non-spore forming rod bacillus is 4 736 949 bp long and contains 3947 protein-coding genes. Genomic analysis identified 173 genes as ORFans (4.5%) and 1650 orthologous proteins (42%) not shared with the closest phylogenetic species, Butyricimonas virosa. Its major fatty acid was the branched acid iso-C15:0 (62.3%).

  9. Butyricimonas phoceensis sp. nov., a new anaerobic species isolated from the human gut microbiota of a French morbidly obese patient

    Directory of Open Access Journals (Sweden)

    A.H. Togo

    2016-11-01

    Full Text Available Butyricimonas phoceensis strain AT9 (= CSUR 2478 = DSM 100838 was isolated from a stool sample from a morbidly obese French patient living in Marseille using the culturomics approach. The genome of this Gram-negative-staining, anaerobic and non–spore forming rod bacillus is 4 736 949 bp long and contains 3947 protein-coding genes. Genomic analysis identified 173 genes as ORFans (4.5% and 1650 orthologous proteins (42% not shared with the closest phylogenetic species, Butyricimonas virosa. Its major fatty acid was the branched acid iso-C15:0 (62.3%.

  10. Bariatric surgery in morbidly obese insulin resistant humans normalises insulin signalling but not insulin-stimulated glucose disposal.

    Directory of Open Access Journals (Sweden)

    Mimi Z Chen

    Full Text Available Weight-loss after bariatric surgery improves insulin sensitivity, but the underlying molecular mechanism is not clear. To ascertain the effect of bariatric surgery on insulin signalling, we examined glucose disposal and Akt activation in morbidly obese volunteers before and after Roux-en-Y gastric bypass surgery (RYGB, and compared this to lean volunteers.The hyperinsulinaemic euglycaemic clamp, at five infusion rates, was used to determine glucose disposal rates (GDR in eight morbidly obese (body mass index, BMI=47.3 ± 2.2 kg/m(2 patients, before and after RYGB, and in eight lean volunteers (BMI=20.7 ± 0.7 kg/m2. Biopsies of brachioradialis muscle, taken at fasting and insulin concentrations that induced half-maximal (GDR50 and maximal (GDR100 GDR in each subject, were used to examine the phosphorylation of Akt-Thr308, Akt-473, and pras40, in vivo biomarkers for Akt activity.Pre-operatively, insulin-stimulated GDR was lower in the obese compared to the lean individuals (P<0.001. Weight-loss of 29.9 ± 4 kg after surgery significantly improved GDR50 (P=0.004 but not GDR100 (P=0.3. These subjects still remained significantly more insulin resistant than the lean individuals (p<0.001. Weight loss increased insulin-stimulated skeletal muscle Akt-Thr308 and Akt-Ser473 phosphorylation, P=0.02 and P=0.03 respectively (MANCOVA, and Akt activity towards the substrate PRAS40 (P=0.003, MANCOVA, and in contrast to GDR, were fully normalised after the surgery (obese vs lean, P=0.6, P=0.35, P=0.46, respectively.Our data show that although Akt activity substantially improved after surgery, it did not lead to a full restoration of insulin-stimulated glucose disposal. This suggests that a major defect downstream of, or parallel to, Akt signalling remains after significant weight-loss.

  11. Genetics of obesity

    African Journals Online (AJOL)

    Rabah M. Shawky

    2011-12-09

    Dec 9, 2011 ... Body weight regulation and stability depends upon an axis with three interrelated components: food intake, energy expen- diture and adipogenesis, although there are still many un- known features concerning fuel homoeostasis and energy balance. There are 358 studies on obese humans reporting po-.

  12. Invariant NKT cells and CD1d(+) cells amass in human omentum and are depleted in patients with cancer and obesity.

    LENUS (Irish Health Repository)

    Lynch, Lydia

    2012-02-01

    Invariant NKT (iNKT) cells recognize lipid antigens presented by CD1d and respond rapidly by killing tumor cells and release cytokines that activate and regulate adaptive immune responses. They are essential for tumor rejection in various mouse models, but clinical trials in humans involving iNKT cells have been less successful, partly due to their rarity in humans compared with mice. Here we describe an accumulation of functional iNKT cells in human omentum, a migratory organ with healing properties. Analysis of 39 omental samples revealed that T cells are the predominant lymphoid cell type and of these, 10% expressed the invariant Valpha24Jalpha18 TCR chain, found on iNKT cells, higher than in any other human organ tested to date. About 15% of omental hematopoietic cells expressed CD1d, compared with 1% in blood (p<0.001). Enriched omental iNKT cells killed CD1d(+) targets and released IFN-gamma and IL-4 upon activation. Omental iNKT-cell frequencies were lower in patients with severe obesity (p=0.005), and with colorectal carcinoma (p=0.004) compared with lean healthy subjects. These data suggest a novel role for the omentum in immune regulation and tumor immunity and identify it as a potential source of iNKT cells for therapeutic use.

  13. FA1 Induces Pro-Inflammatory and Anti-Adipogenic Pathways/Markers in Human Myotubes Established from Lean, Obese, and Type 2 Diabetic Subjects but Not Insulin Resistance

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Beck-Nielsen, Henning; Gaster, Michael

    2013-01-01

    /FA1 in insulin resistance and type 2 diabetes in human subjects, we studied the effects of chronic FA1 on the intermediary metabolism in myotubes established from lean, obese, and type 2 diabetic (T2D) subjects. Methods: Myotube cultures were established from lean and obese control subjects......Aims: Delta like 1/fetal antigen 1 (Dlk1/FA1) is a protein secreted by hormone producing cells in adult human and mice that is known to inhibit adipogenesis. Recent studies demonstrated the role of Dlk1/FA1 in inducing insulin resistance in mice. To investigate the involvement of circulating Dlk1......, and obese T2D subjects and treated with soluble FA1 for 4 days supplemented with/without palmitate (PA). Lipid- and glucose metabolism were studied with labeled precursors while quantitative expression of genes was analyzed using real-time PCR. Results: Diabetic myotubes express significantly reduced...

  14. Preclinical models for obesity research

    Directory of Open Access Journals (Sweden)

    Perry Barrett

    2016-11-01

    Full Text Available A multi-dimensional strategy to tackle the global obesity epidemic requires an in-depth understanding of the mechanisms that underlie this complex condition. Much of the current mechanistic knowledge has arisen from preclinical research performed mostly, but not exclusively, in laboratory mouse and rat strains. These experimental models mimic certain aspects of the human condition and its root causes, particularly the over-consumption of calories and unbalanced diets. As with human obesity, obesity in rodents is the result of complex gene–environment interactions. Here, we review the traditional monogenic models of obesity, their contemporary optogenetic and chemogenetic successors, and the use of dietary manipulations and meal-feeding regimes to recapitulate the complexity of human obesity. We critically appraise the strengths and weaknesses of these different models to explore the underlying mechanisms, including the neural circuits that drive behaviours such as appetite control. We also discuss the use of these models for testing and screening anti-obesity drugs, beneficial bio-actives, and nutritional strategies, with the goal of ultimately translating these findings for the treatment of human obesity.

  15. Similarities between obesity in pets and children : the addiction model

    NARCIS (Netherlands)

    Pretlow, Robert A; Corbee, Ronald J

    2016-01-01

    Obesity in pets is a frustrating, major health problem. Obesity in human children is similar. Prevailing theories accounting for the rising obesity rates - for example, poor nutrition and sedentary activity - are being challenged. Obesity interventions in both pets and children have produced modest

  16. OVERWEIGHT/OBESITY AND HUMAN CAPITAL FORMATION FROM INFANCY TO ADOLESCENCE: EVIDENCE FROM TWO LARGE US COHORTS.

    Science.gov (United States)

    Murasko, Jason E

    2015-03-01

    Body mass index (BMI) levels in US children and adolescents have increased over the past several decades. The negative health effects of this trend are well-documented. Recent work has evaluated the potential effects on skills formation. Studies are mixed on whether there is an association between high BMI and skills outcomes, and those that estimate causal effects find none. This paper offers estimates on the causal effect of BMI-defined overweight and obesity on skills formation using two large cohorts of contemporary US children followed from infancy to 5 years and from kindergarten (6 years) to the eighth grade (14 years). Significant negative associations were observed in the random effects models for males in early life with respect to a mental skills assessment, for females during the pre-school years for reading and maths assessments, for both males and females during the schooling years for reading assessments and for females during the schooling years for maths assessments. Fixed effects models yielded a significant negative association only with respect to the latter. The implication of these findings is that any improvement in skills outcomes that may accompany reductions in obesity prevalence may depend on whether interventions are general to overall health productivity or whether they are specific to dietary and exercise behaviours.

  17. [Pathophysiology and genetics of obesity].

    Science.gov (United States)

    Oberkofler, Hannes; Krempler, Franz; Patsch, Wolfgang

    2002-01-01

    Obesity has become the most prevalent nutritional disorder in post-industrialised societies and it is associated with the development of severe and costly complications such as type 2 diabetes mellitus and coronary heart disease or cancer. A large proportion of the risk of obesity is determined by the genetic susceptibility of an individual, but environmental factors conducive for the disorder play an important role in its phenotypic expression. Several candidate genes emerged from studies in animal models of obesity, but human pathophysiology is likely to be more complex. Thus, most cases of human obesity probably result from subtle interactions of susceptibility genes with environmental factors favouring deposition of excess calories as fat. The recent surge of obesity may relate to past evolutionary pressure which favoured selection of mechanisms defending body-weight against caloric restriction rather than against caloric excess. Rapidly developing new techniques in quantitative genetics and growing information from functional genomics will help to understand the interaction of environmental factors with signalling networks that regulate energy metabolism. The role of previously unknown pathways in the aetiology of obesity will be uncovered. The typing of numerous genetic variants will become possible and allow individual risk assessment for obesity and/or its associated disorders. Thus, rational and individually tailored therapies may be developed to combat obesity and its associated disorders.

  18. Morbidly obese human subjects have increased peripheral blood CD4 + T cells with skewing toward a Treg- and Th2-dominated phenotype

    NARCIS (Netherlands)

    K. van der Weerd (Kim); W.A. Dik (Willem); B. Schrijver (Benjamin); D.H. Schweitzer (Dave ); A.W. Langerak (Anton); H.A. Drexhage (Hemmo); R.M. Kiewiet-Kemper (Rosalie); M.O. van Aken (Maarten); A. van Huisstede (Astrid); J.J.M. van Dongen (Jacques); A.J. van der Lelij (Aart Jan); F.J.T. Staal (Frank); P.M. van Hagen (Martin)

    2012-01-01

    textabstractObesity is associated with local T-cell abnormalities in adipose tissue. Systemic obesity-related abnormalities in the peripheral blood T-cell compartment are not well defined. In this study, we investigated the peripheral blood T-cell compartment of morbidly obese and lean subjects. We

  19. Macrophages and Adipocytes in Human Obesity Adipose Tissue Gene Expression and Insulin Sensitivity During Calorie Restriction and Weight Stabilization

    DEFF Research Database (Denmark)

    Capel, F.; Klimcakova, E.; Viguerie, N.

    2009-01-01

    OBJECTIVE-We investigated the regulation of adipose tissue gene expression during different phases of a dietary weight loss program and its relation with insulin sensitivity. RESEARCH DESIGN AND METHODS-Twenty-two obese women followed a dietary intervention program composed of an energy restriction...... macrophages and adipocytes show distinct patterns of gene regulation and association with insulin sensitivity during the various phases of a dietary weight loss program. Diabetes 58:1558-1567, 2009...... phase with a 4-week very-low-calorie diet and a weight stabilization period composed of a 2-month low-calorie diet followed by 3-4 months of a weight maintenance diet. At each time point, a euglycemic-hyperinsulinemic clamp and subcutaneous adipose tissue biopsies were performed. Adipose tissue gene...

  20. Orlistat (Ro 18-0647), a lipase inhibitor, in the treatment of human obesity: a multiple dose study.

    Science.gov (United States)

    Drent, M L; Larsson, I; William-Olsson, T; Quaade, F; Czubayko, F; von Bergmann, K; Strobel, W; Sjöström, L; van der Veen, E A

    1995-04-01

    To evaluate efficacy and tolerability of the lipase inhibitor Orlistat (Ro 18-0647) in doses of 10, 60 and 120 mg three times a day in addition to a mild hypocaloric diet containing 30% of calories as fat. 4 week single-blind placebo run-in period of diet alone followed by a 12 week double-blind, placebo-controlled, randomized treatment period. Five European outpatient clinics specializing in endocrinology and/or the treatment of obesity, one central laboratory. Of 237 healthy obese subjects meeting the inclusion criteria, 188 showed compliance to the diet during the run-in period and were randomized for the treatment period. Primary efficacy criterion was the difference in weight loss after 12 weeks of treatment between the Orlistat treated groups and the diet alone group. Secondary efficacy criteria were changes in serum total, HDL- and LDL-cholesterol. Compared to placebo a mean (+/- s.e.) additional weight loss of 0.63 +/- 0.54 kg with 30 mg a day (P = 0.246), 0.71 +/- 0.55 kg with 180 mg a day (P = 0.190) and 1.75 +/- 0.54 kg with 360 mg a day was seen (P = 0.001) or Orlistat was observed. Overall data indicated dose-dependency. Small decreases were seen in total and LDL-cholesterol (significant in the 180 and 360 mg a day groups) and LDL- to HDL-cholesterol ratio (significant in the 360 mg a day group only). Mild, mostly gastrointestinal side effects were observed more frequently in the Orlistat groups and caused premature withdrawal from the study in only four patients. No marked laboratory abnormalities were shown, including the lipid-soluble vitamins A, D and E. Orlistat, in an apparently dose-dependent manner, leads to additional weight loss compared to diet alone and overall, is well tolerated.

  1. Childhood obesity.

    Science.gov (United States)

    Sabin, M A; Shield, J P H

    2008-01-01

    The prevalence of childhood obesity continues to increase worldwide. Its presence is associated with significant adverse effects on health including an increased propensity to type II diabetes, cardiovascular, respiratory, and liver disease. In the vast majority of children, obesity is lifestyle-related, yet there is a dearth of evidence on how to best develop effective prevention and treatment strategies. This review outlines the importance of childhood and adolescent growth on long-term health, the definitions used to define obesity in children (along with up-to-date prevalence data), causes and consequences, and aspects of prevention and management.

  2. Polymorphic human (CTAT)n microsatellite provides a conserved linkage marker for mouse mutants causing cleft palate, vestibular defects, obesity and ataxia

    Energy Technology Data Exchange (ETDEWEB)

    Griffith, A.J.; Burgess, D.L.; Kohrman, D. [Univ. of MIchigan, Ann Arbor, MI (United States)] [and others

    1994-09-01

    The Twirler mutation (Tw) causing cleft palate {plus_minus} cleft lip, vestibular defects and obesity is located within 0.5 cM of an ataxia locus (ax) on mouse chromosome 18. We identified a transgene-induced insertional mutation with vestibular and craniofacial defects that appears to be a new allele of Twirler. Mouse DNA flanking the transgene insertion site was isolated from a cosmid library. An evolutionarily conserved, zoo blot positive cosmid subclone was used to probe a human {lambda} genomic library. From the sequence of a highly homologous human {lambda} clone, we designed STS primers and screened a human P1 library. DNA from two positive P1 clones was hybridized with simple sequence probes, and a (CTAT){sub 12} repeat was detected. Analysis of 62 CEPH parents with primers flanking the repeat identified six alleles containing 9 to 14 copies of the repeat, at frequencies of 0.17, 0.17, 0.17, 0.27, 0.15 and 0.07, respectively. The observed heterozygosity was 49/62 with a calculated PIC value of 0.76. This polymorphic microsatellite marker, designated Umi3, was mapped to the predicted conserved human linkage group by analysis of somatic cell hybrid panels. The anticipated short distance between Umi3 and the disease genes will facilitate detection of linkage in small families. We would like to type appropriate human pedigrees with Umi3 in order to identify patients with inherited disorders homologous to the mouse mutations Twirler and ataxia.

  3. Mood, food, and obesity.

    Science.gov (United States)

    Singh, Minati

    2014-01-01

    Food is a potent natural reward and food intake is a complex process. Reward and gratification associated with food consumption leads to dopamine (DA) production, which in turn activates reward and pleasure centers in the brain. An individual will repeatedly eat a particular food to experience this positive feeling of gratification. This type of repetitive behavior of food intake leads to the activation of brain reward pathways that eventually overrides other signals of satiety and hunger. Thus, a gratification habit through a favorable food leads to overeating and morbid obesity. Overeating and obesity stems from many biological factors engaging both central and peripheral systems in a bi-directional manner involving mood and emotions. Emotional eating and altered mood can also lead to altered food choice and intake leading to overeating and obesity. Research findings from human and animal studies support a two-way link between three concepts, mood, food, and obesity. The focus of this article is to provide an overview of complex nature of food intake where various biological factors link mood, food intake, and brain signaling that engages both peripheral and central nervous system signaling pathways in a bi-directional manner in obesity.

  4. Mood, food, and obesity

    Directory of Open Access Journals (Sweden)

    Minati eSingh

    2014-09-01

    Full Text Available Food is a potent natural reward and food intake is a complex process. Reward and gratification associated with food consumption leads to dopamine (DA production, which in turn activates reward and pleasure centers in the brain. An individual will repeatedly eat a particular food to experience this positive feeling of gratification. This type of repetitive behavior of food intake leads to the activation of brain reward pathways that eventually overrides other signals of satiety and hunger. Thus, a gratification habit through a favorable food leads to overeating and morbid obesity. Overeating and obesity stems from many biological factors engaging both central and peripheral systems in a bi-directional manner involving mood and emotions. Emotional eating and altered mood can also lead to altered food choice and intake leading to overeating and obesity. Research findings from human and animal studies support a two-way link between three concepts, mood, food, and obesity. The focus of this article is to provide an overview of complex nature of food intake where various biological factors link mood, food intake, and brain signaling that engages both peripheral and central nervous system signaling pathways in a bi-directional manner in obesity.

  5. Mood, food, and obesity

    Science.gov (United States)

    Singh, Minati

    2014-01-01

    Food is a potent natural reward and food intake is a complex process. Reward and gratification associated with food consumption leads to dopamine (DA) production, which in turn activates reward and pleasure centers in the brain. An individual will repeatedly eat a particular food to experience this positive feeling of gratification. This type of repetitive behavior of food intake leads to the activation of brain reward pathways that eventually overrides other signals of satiety and hunger. Thus, a gratification habit through a favorable food leads to overeating and morbid obesity. Overeating and obesity stems from many biological factors engaging both central and peripheral systems in a bi-directional manner involving mood and emotions. Emotional eating and altered mood can also lead to altered food choice and intake leading to overeating and obesity. Research findings from human and animal studies support a two-way link between three concepts, mood, food, and obesity. The focus of this article is to provide an overview of complex nature of food intake where various biological factors link mood, food intake, and brain signaling that engages both peripheral and central nervous system signaling pathways in a bi-directional manner in obesity. PMID:25225489

  6. Obesity and female infertility: potential mediators of obesity's impact.

    Science.gov (United States)

    Broughton, Darcy E; Moley, Kelle H

    2017-04-01

    The worldwide upward trend in obesity has been dramatic, now affecting more than 20% of American women of reproductive age. Obesity is associated with many adverse maternal and fetal effects prenatally, but it also exerts a negative influence on female fertility. Obese women are more likely to have ovulatory dysfunction due to dysregulation of the hypothalamic-pituitary-ovarian axis. Women with polycystic ovarian syndrome who are also obese demonstrate a more severe metabolic and reproductive phenotype. Obese women have reduced fecundity even when eumenorrheic and demonstrate poorer outcomes with the use of in vitro fertilization. Obesity appears to affect the oocyte and the preimplantation embryo, with disrupted meiotic spindle formation and mitochondrial dynamics. Excess free fatty acids may have a toxic effect in reproductive tissues, leading to cellular damage and a chronic low-grade inflammatory state. Altered levels of adipokines, such as leptin, in the obese state can affect steroidogenesis and directly affect the developing embryo. The endometrium is also susceptible, with evidence of impaired stromal decidualization in obese women. This may explain subfecundity due to impaired receptivity, and may lead to placental abnormalities as manifested by higher rates of miscarriage, stillbirth, and preeclampsia in the obese population. Many interventions have been explored to mitigate the effect of obesity on infertility, including weight loss, physical activity, dietary factors, and bariatric surgery. These data are largely mixed, with few high quality studies to guide us. As we improve our understanding of the pathophysiology of obesity in human reproduction we hope to identify novel treatment strategies. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  7. Obesity: genome and environment interactions.

    Science.gov (United States)

    Bašić, Martina; Butorac, Ana; Landeka Jurčević, Irena; Bačun-Družina, Višnja

    2012-09-01

    Obesity has become one of the major threats for public health in industrialised world among adults, but also among adolescents and children. It is influenced by the interaction of genes, nutrition, environment, and lifestyle. Environmental and lifestyle risk factors include foetal and lifelong environment, nutrient quality, chemical and microbial exposure, and psychical stress, all of which are important contributing influences. Removing or limiting chemical and pharmaceutical obesogens from human environment could make a difference in the growing epidemic of obesity. Additionally, nutrigenomics describes how modifications in individual diets can improve health and prevent chronic diseases, as well as obesity, by understanding the effects of a genetic profile in the interaction between food and increase in body weight. Furthermore, individual genetic variations in genome represent an individual's predisposition for obesity. Therefore, the use of individual genetic information, avoiding obesogens, and a healthy lifestyle could help to improve the management of obesity and maintain a healthy weight.

  8. Obese people=Animals? Investigating the implicit “animalization” of obese people

    Directory of Open Access Journals (Sweden)

    Bernard, P.

    2015-01-01

    Full Text Available Integrating a dehumanization perspective with the literature on stereotyping of obesity, this paper investigated whether obese people are implicitly categorized as animals rather than humans. Sixty participants were asked to complete an Implicit Association Test in which they had to associate images of thin and obese faces with animal or human characteristics. As predicted, people were more likely to categorize images of obese faces as animal-like and this tendency was more acute amongst thinner participants. Implications of our results for future on research on dehumanization and negative stereotyping of obesity are discussed.

  9. Obesity-Related Metabolomic Analysis of Human Subjects in Black Soybean Peptide Intervention Study by Ultraperformance Liquid Chromatography and Quadrupole-Time-of-Flight Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Min Jung Kim

    2013-01-01

    Full Text Available The present study aimed to identify key metabolites related to weight reduction in humans by studying the metabolic profiles of sera obtained from 34 participants who underwent dietary intervention with black soybean peptides (BSP for 12 weeks. This research is a sequel to our previous work in which the effects of BSP on BMI and blood composition of lipid were investigated. Sera of the study were subjected to ultra performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS, and the data were analyzed using partial least-squares discriminate analysis (PLS-DA score plots. Body mass index and percent body fat of the test group were reduced. Levels of betaine, benzoic acid, pyroglutamic acid, pipecolic acid, N-phenylacetamide, uric acid, l-aspartyl-l-phenylalanine, and lysophosphatidyl cholines (lysoPCs (C18:1, C18:2, C20:1, and C20:4 showed significant increases. Levels of l-proline, valine, l-leucine/isoleucine, hypoxanthine, glutamine, l-methionine, phenylpyruvic acid, several carnitine derivatives, and lysoPCs (C14:0, PC16:0, C15:0, C16:0, C17:1, C18:0, and C22:0 were significantly decreased. In particular, lysoPC 16:0 with a VIP value of 12.02 is esteemed to be the most important metabolite for evaluating the differences between the 2 serum samples. Our result confirmed weight-lowering effects of BSP, accompanied by favorable changes in metabolites in the subjects’ blood. Therefore, this research enables us to better understand obesity and increases the predictability of the obesity-related risk by studying metabolites present in the blood.

  10. Cancer and Obesity

    Science.gov (United States)

    ... Kit Read the MMWR Science Clips Cancer and obesity Overweight and obesity are associated with cancer Language: ... a cancer associated with overweight and obesity. Problem Obesity is a leading cancer risk factor. What’s happening? ...

  11. The effects of soy isoflavones on obesity

    DEFF Research Database (Denmark)

    Ørgaard, Anne; Jensen, Lotte

    2008-01-01

    Over the last decades, the prevalence of obesity and related diseases has increased rapidly in the Western world. Obesity is a disorder of energy balance and is associated with hyper-insulinemia, insulin resistance, and abnormalities in lipid metabolism, and it is one of the most important risk...... and daidzein can be obtained in high levels in humans under certain nutritional conditions, and epidemiologic and laboratory data suggest that these compounds could have health benefits in human obesity. This review will focus on the latest results of research on isoflavones and their effect on obesity in cell...

  12. A whey-protein supplement increases fat loss and spares lean muscle in obese subjects: a randomized human clinical study

    Directory of Open Access Journals (Sweden)

    Ward Loren S

    2008-03-01

    reduce the risk of obesity related disease, the results have practical significance.

  13. Childhood obesity

    DEFF Research Database (Denmark)

    Heitmann, Berit L; Koplan, Jeffrey; Lissner, Lauren

    2009-01-01

    Despite progress toward assuring the health of today's young population, the 21(st) century began with an epidemic of childhood obesity. There is general agreement that the situation must be addressed by means of primary prevention, but relatively little is known about how to intervene effectively....... The evidence behind the assumption that childhood obesity can be prevented was discussed critically in this roundtable symposium. Overall, there was general agreement that action is needed and that the worldwide epidemic itself is sufficient evidence for action. As the poet, writer, and scholar Wittner Bynner...

  14. Randomized trial on the effects of a 7-d low-glycemic diet and exercise intervention on insulin resistance in older obese humans

    DEFF Research Database (Denmark)

    Solomon, Thomas; Haus, Jacob M; Kelly, Karen R

    2009-01-01

    The optimal combination of diet and exercise that produces the greatest reversal of obesity-related insulin resistance is unknown.......The optimal combination of diet and exercise that produces the greatest reversal of obesity-related insulin resistance is unknown....

  15. Satellite cells derived from obese humans with type 2 diabetes and differentiated into myocytes in vitro exhibit abnormal response to IL-6

    DEFF Research Database (Denmark)

    Scheele, Camilla; Nielsen, Søren; Broholm, Christa

    2012-01-01

    a resistance to IL-6. By utilizing western blot analysis, we demonstrate that IL-6Rα protein was down regulated in skeletal muscle biopsies from obese persons with and without type 2 diabetes. To further investigate the status of IL-6 signaling in skeletal muscle in obesity-associated type 2 diabetes, we...

  16. Role of Macrophage Migration Inhibitory Factor in Obesity, Insulin Resistance, Type 2 Diabetes, and Associated Hepatic Co-Morbidities: A Comprehensive Review of Human and Rodent Studies

    NARCIS (Netherlands)

    Morrison, M.C.; Kleemann, R.

    2015-01-01

    Obesity is associated with a chronic low-grade inflammatory state that drives the -development of obesity-related co-morbidities such as insulin resistance/type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. This metabolic inflammation is thought to originate in

  17. Obesity and Insulin Resistance: Management in Diabetes

    OpenAIRE

    Suhel Ashraff; Muhammad A. Siddiqui; Thomas E. Carline

    2013-01-01

    Obesity today, is a major public health problem across the world. The rapid increase in the incidence of obesity and associated co-morbidities presents a major challenge to health care globally. Insulin resistance is commonly associated with obesity and other life style diseases. However, much uncertainty remains about the mechanism regarding the association between insulin resistance and human disease mainly because of the difficulties of defining insulin resistance in clinical terms and of ...

  18. Sirtuins 1-7 expression in human adipose-derived stem cells from subcutaneous and visceral fat depots: influence of obesity and hypoxia.

    Science.gov (United States)

    Mariani, Stefania; Di Rocco, Giuliana; Toietta, Gabriele; Russo, Matteo A; Petrangeli, Elisa; Salvatori, Luisa

    2017-09-01

    The sirtuin family comprises seven NAD + -dependent deacetylases which control the overall health of organisms through the regulation of pleiotropic metabolic pathways. Sirtuins are important modulators of adipose tissue metabolism and their expression is higher in lean than obese subjects. At present, the role of sirtuins in adipose-derived stem cells has not been investigated yet. Therefore, in this study, we evaluated the expression of the complete panel of sirtuins in adipose-derived stem cells isolated from both subcutaneous and visceral fat of non-obese and obese subjects. We aimed at investigating the influence of obesity on sirtuins' levels, their role in obesity-associated inflammation, and the relationship with the peroxisome proliferator-activated receptor delta, which also plays functions in adipose tissue metabolism. The mRNA levels in the four types of adipose-derived stem cells were evaluated by quantitative polymerase chain reaction, in untreated cells and also after 8 h of hypoxia exposure. Correlations among sirtuins' expression and clinical and molecular parameters were also analyzed. We found that sirtuin1-6 exhibited significant higher mRNA expression in visceral adipose-derived stem cells compared to subcutaneous adipose-derived stem cells of non-obese subjects. Sirtuin1-6 levels were markedly reduced in visceral adipose-derived stem cells of obese patients. Sirtuins' expression in visceral adipose-derived stem cells correlated negatively with body mass index and C-reactive protein and positively with peroxisome proliferator-activated receptor delta. Finally, only in the visceral adipose-derived stem cells of obese patients hypoxia-induced mRNA expression of all of the sirtuins. Our results highlight that sirtuins' levels in adipose-derived stem cells are consistent with protective effects against visceral obesity and inflammation, and suggest a transcriptional mechanism through which acute hypoxia up-regulates sirtuins in the visceral

  19. Potentiation of response to insulin and anti-insulin action by two human pituitary peptides in lean agouti A/a, obese yellow Avy/A, and C57BL/6J-ob/ob mice.

    Science.gov (United States)

    Salem, M A; Wolff, G L

    1989-06-01

    Insulin-like and anti-insulin effects of human growth hormone (hGH) were examined by determining the effects of two peptides representing portions of the hGH molecule in lean agouti A/a and obese yellow Avy/A and ob/ob mice. The peptides were the amino terminal segment, residue 1-43 (hGH1-43), which has been shown to potentiate the response to insulin and another peptide, hyperglycemic peptide (HP), with unknown structure, which has anti-insulin activity. The anti-insulin component is an acidic low molecular weight peptide which co-purifies with hGH but was not recognized by antibodies to intact hGH and did not cross-react with anti-hGH1-43 antiserum. The purpose of these studies was to further understand the multiple actions of hGH and its acute and chronic effects on response to insulin. Injections of hGH1-43 dramatically enhanced the effect of insulin on glucose clearance of obese yellow Avy/A and ob/ob mice and increased the insulin-stimulated glucose oxidation in adipose tissue of yellow mice, but had no direct effect on blood glucose or insulin levels of either genotype. Administration of HP to obese yellow mice produced hyperglycemia and suppressed serum insulin concentrations. Tissues from lean agouti and obese yellow mice treated with HP in vitro showed decreased basal and insulin-stimulated glucose oxidation as well as decreased 14C incorporation into lipids. Chronic treatment of obese yellow and ob/ob mice with HP increased fasting blood glucose and impaired glucose tolerance. The effect of HP was more pronounced in obese yellow mice and the ob/ob mice were more sensitive to the diabetogenic actions of intact hGH. These data provide further evidence for the existence of two opposing biologic activities derived from disparate amino acid sequences in hGH. Additionally, the data indicate that assays using obese yellow Avy/A mice can distinguish the effects of hGH from those of the individual peptides to a greater degree than assays using obese ob/ob mice.

  20. A narrative review of physical activity, nutrition, and obesity to cognition and scholastic performance across the human lifespan.

    Science.gov (United States)

    Burkhalter, Toni M; Hillman, Charles H

    2011-03-01

    We reviewed studies that examine the relationship of energy consumption, storage, and expenditure to cognition and scholastic performance. Specifically, the literature base on nutrient intake, body mass, and physical activity is described relative to cognitive development and academic achievement. The review of literature regarding the overconsumption of energy and excess body mass suggests poorer academic achievement during development and greater decay of brain structure and function accompanied by increased cognitive aging during older adulthood. The review of literature regarding energy expenditure through the adoption of increased physical activity participation suggests increased cognitive health and function. Although this area of study is in its infancy, the preliminary data are promising and matched with the declining physical health of industrialized nations; this area of science could provide insight aimed at improving brain health and cognitive function across the human lifespan.

  1. The gut microbiota, obesity and insulin resistance

    Science.gov (United States)

    The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflam...

  2. Are there healthy obese?

    Science.gov (United States)

    Griera Borrás, José Luis; Contreras Gilbert, José

    2014-01-01

    It is currently postulated that not all obese individuals have to be considered as pathological subjects. From 10% to 20% of obese people studied do not show the metabolic changes common in obese patients. The term "healthy obese" has been coined to refer to these patients and differentiate them from the larger and more common group of pathological obese subjects. However, the definition of "healthy obese" is not clear. Use of "healthy obese" as a synonym for obese without metabolic complications is risky. Clinical markers such as insulin resistance are used to identify this pathology. It is not clear that healthy obese subjects have lower morbidity and mortality than pathologically obese patients. According to some authors, healthy obese would represent an early stage in evolution towards pathological obesity. There is no agreement as to the need to treat healthy obese subjects. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  3. Elevated NF-κB activation is conserved in human myocytes cultured from obese type 2 diabetic patients and attenuated by AMP-activated protein kinase

    DEFF Research Database (Denmark)

    Green, Charlotte Jane; Pedersen, Maria; Pedersen, Bente K

    2011-01-01

    To examine whether the inflammatory phenotype found in obese and diabetic individuals is preserved in isolated, cultured myocytes and to assess the effectiveness of pharmacological AMP-activated protein kinase (AMPK) activation upon the attenuation of inflammation in these myocytes....

  4. Caloric restriction and diet-induced weight loss do not induce browning of human subcutaneous white adipose tissue in women and men with obesity

    DEFF Research Database (Denmark)

    Barquissau, Valentin; Léger, Benjamin; Beuzelin, Diane

    2018-01-01

    Caloric restriction (CR) is standard lifestyle therapy in obesity management. CR-induced weight loss improves the metabolic profile of individuals with obesity. In mice, occurrence of beige fat cells in white fat depots favors a metabolically healthy phenotype, and CR promotes browning of white...... variation, with higher expression of brown and beige markers in women with obesity and during winter, respectively. The very low calorie diet resulted in decreased browning of subcutaneous abdominal WAT. During the whole dietary intervention, evolution of body fat and insulin resistance was independent...... of changes in brown and beige fat markers. These data suggest that diet-induced effects on body fat and insulin resistance are independent of subcutaneous abdominal WAT browning in people with obesity....

  5. Ovarian hormones and obesity.

    Science.gov (United States)

    Leeners, Brigitte; Geary, Nori; Tobler, Philippe N; Asarian, Lori

    2017-05-01

    central action of estrogens to increase the satiating potency of the gastrointestinal hormone cholecystokinin. Another mechanism involves a decrease in the preference for sweet foods during the follicular phase. Genetic defects in brain α-melanocycte-stimulating hormone-melanocortin receptor (melanocortin 4 receptor, MC4R) signaling lead to a syndrome of overeating and obesity that is particularly pronounced in women and in female animals. The syndrome appears around puberty in mice with genetic deletions of MC4R, suggesting a role of ovarian hormones. Emerging functional brain-imaging data indicates that fluctuations in ovarian hormones affect eating by influencing striatal dopaminergic processing of flavor hedonics and lateral prefrontal cortex processing of cognitive inhibitory controls of eating. There is a dearth of research on the neuroendocrine control of eating after menopause. There is also comparatively little research on the effects of ovarian hormones on EE, although changes in ovarian hormone levels during the menstrual cycle do affect resting EE. The markedly greater obesity burden in women makes understanding the diverse effects of ovarian hormones on eating, EE and body adiposity urgent research challenges. A variety of research modalities can be used to investigate these effects in women, and most of the mechanisms reviewed are accessible in animal models. Therefore, human and translational research on the roles of ovarian hormones in women's obesity and its causes should be intensified to gain further mechanistic insights that may ultimately be translated into novel anti-obesity therapies and thereby improve women's health. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  6. Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects—A Narrative Review of Human and Animal Evidence

    OpenAIRE

    Howell, Anthony; Harvie, Michelle

    2017-01-01

    Intermittent energy restriction (IER) has become popular as a means of weight control amongst people who are overweight and obese, and is also undertaken by normal weight people hoping spells of marked energy restriction will optimise their health. This review summarises randomised comparisons of intermittent and isoenergetic continuous energy restriction for weight loss to manage overweight and obesity. It also summarises the potential beneficial or adverse effects of IER on body composition...

  7. Human hepatic lipase overexpression in mice induces hepatic steatosis and obesity through promoting hepatic lipogenesis and white adipose tissue lipolysis and fatty acid uptake.

    Directory of Open Access Journals (Sweden)

    Lídia Cedó

    Full Text Available Human hepatic lipase (hHL is mainly localized on the hepatocyte cell surface where it hydrolyzes lipids from remnant lipoproteins and high density lipoproteins and promotes their hepatic selective uptake. Furthermore, hepatic lipase (HL is closely associated with obesity in multiple studies. Therefore, HL may play a key role on lipid homeostasis in liver and white adipose tissue (WAT. In the present study, we aimed to evaluate the effects of hHL expression on hepatic and white adipose triglyceride metabolism in vivo. Experiments were carried out in hHL transgenic and wild-type mice fed a Western-type diet. Triglyceride metabolism studies included β-oxidation and de novo lipogenesis in liver and WAT, hepatic triglyceride secretion, and adipose lipoprotein lipase (LPL-mediated free fatty acid (FFA lipolysis and influx. The expression of hHL promoted hepatic triglyceride accumulation and de novo lipogenesis without affecting triglyceride secretion, and this was associated with an upregulation of Srebf1 as well as the main genes controlling the synthesis of fatty acids. Transgenic mice also exhibited more adiposity and an increased LPL-mediated FFA influx into the WAT without affecting glucose tolerance. Our results demonstrate that hHL promoted hepatic steatosis in mice mainly by upregulating de novo lipogenesis. HL also upregulated WAT LPL and promoted triglyceride-rich lipoprotein hydrolysis and adipose FFA uptake. These data support the important role of hHL in regulating hepatic lipid homeostasis and confirm the broad cardiometabolic role of HL.

  8. Leptin, obesity and cardiovascular disease.

    Science.gov (United States)

    Correia, Marcelo Lima de Gusmao; Haynes, William Geoffrey

    2004-03-01

    Obesity is a risk factor for cardiovascular diseases. Leptin levels are increased in obesity and leptin exhibits cardiovascular actions that may contribute to increased cardiovascular risk. We review the sympathetic, renal and vascular actions of leptin and their relevance to cardiovascular disease. Leptin possesses cardio-renal actions potentially contributing to obesity-related hypertension including generalized sympathoactivation. However, given that leptin resistance occurs in obesity, it has been difficult to link hyperleptinemia with hypertension. One possibility is that leptin resistance is confined to the metabolic effects of leptin, with preservation of its sympathoexcitatory actions. Other mechanisms may contribute to the pressor effects of leptin. For instance, angiotensin II induces leptin generation. Leptin also potentiates the pressor effect of insulin. Therefore, interactions between angiotensin II and insulin with leptin could have deleterious cardiovascular effects in obesity. Additionally, leptin appears to stimulate vascular inflammation, oxidative stress and hypertophy. These actions may contribute to the pathogenesis of hypertension, atherosclerosis, and left ventricular hypertrophy. The potential actions of leptin in the pathophysiology of cardiovascular complications of obesity are diverse, despite evidence of leptin resistance to its metabolic actions. However, most information about cardiovascular actions of leptin derives from in-vitro and animal studies. Future research in humans is widely awaited.

  9. Hormones and Obesity

    Science.gov (United States)

    ... Weight Loss Featured Resource Find an Endocrinologist Search Obesity September 2017 Download PDFs English Espanol Editors Durga ... Resources Mayo Clinic MedlinePlus NIDDK (NIH) What is obesity? Obesity is a chronic (long-term) medical problem ...

  10. Obesity Hypoventilation Syndrome

    Science.gov (United States)

    ... Home / Obesity Hypoventilation Syndrome Obesity Hypoventilation Syndrome Also known as Pickwickian Syndrome What ... your neck is larger than normal. Complications of Obesity Hypoventilation Syndrome When left untreated, OHS can cause ...

  11. Cancers Associated with Overweight and Obesity Infographic

    Science.gov (United States)

    Overweight and obesity are linked to an increased risk of 13 types of cancer. See a diagram of the human body highlighting the organs or tissues at increased cancer risk, including the breast, colon and rectum, kidney, and liver.

  12. Childhood Overweight and Obesity

    Science.gov (United States)

    ... Wellness Food and Nutrition Healthy Food Choices Childhood Overweight and Obesity: Helping Your Child Achieve a Healthy Weight Childhood Overweight and Obesity: Helping Your Child Achieve a Healthy ...

  13. Why Obesity?

    Science.gov (United States)

    Bray, George A

    2015-01-01

    As Erwin Chargaff observed, "Scientific autobiography belongs to a most awkward literary genre," and mine is no exception. In reviewing my scientific life, I contrast the nutritional influences that would have existed had I been born 100 or 200 years earlier than I actually was. With this background, I trace the influences on my formative years in science beginning in high school and ending as a postdoctoral fellow in Professor E.B. Astwood's laboratory, when my directional sails were set and obesity was the compass heading. With this heading, the need for organized national and international meetings on obesity and the need for a scientific journal dealing with obesity as its subject matter became evident and occupied considerable energy over the next 30 years. The next section of this memoir traces the wanderings of an itinerant academic who moved from Boston to Los Angeles and finally to Baton Rouge. The influence of Sir William Osler's idea that there is a time for education, a time for scholarship, a time for teaching, and time to retire has always been a guide to allocating time ever since I was an intern at Johns Hopkins Hospital. It was in Baton Rouge that the final phase began: I agreed to become the first full-time executive director of the Pennington Biomedical Research Center, a decision that changed my life. The article ends with a quotation from Tennessee Williams that reflects the theater, which has given me so much pleasure over the years: "There is a time for departure even when there's no certain place to go."

  14. Past and future corollaries of theories on causes of metabolic syndrome and obesity related co-morbidities part 2: a composite unifying theory review of human-specific co-adaptations to brain energy consumption.

    Science.gov (United States)

    McGill, Anne-Thea

    2014-01-01

    Metabolic syndrome (MetS) predicts type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer, and their rates have escalated over the last few decades. Obesity related co-morbidities also overlap the concept of the metabolic syndrome (MetS). However, understanding of the syndrome's underlying causes may have been misapprehended. The current paper follows on from a theory review by McGill, A-T in Archives of Public Health, 72: 30. This accompanying paper utilises research on human evolution and new biochemistry to theorise on why MetS and obesity arise and how they affect the population. The basis of this composite unifying theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A 'dual system' is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals. In humans who consume a nutritious diet, the NRF2 system has become highly energy efficient. Other relevant human-specific co-adaptations are explored. In order to 'test' this composite unifying theory it is important to show that the hypothesis and sub-theories pertain throughout the whole of human evolution and history up till the current era. Corollaries of the composite unifying theory of MetS are examined with respect to past under-nutrition and malnutrition since agriculture began 10,000 years ago. The effects of man-made pollutants on degenerative change are examined. Projections are then made from current to future patterns on the state of 'insufficient micronutrient and/or unbalanced high energy malnutrition with central obesity and metabolic dysregulation' or 'malnubesity'. Forecasts

  15. Paradoxical Effects of Fruit on Obesity

    Directory of Open Access Journals (Sweden)

    Satya P. Sharma

    2016-10-01

    Full Text Available Obesity is exponentially increasing regardless of its preventable characteristics. The current measures for preventing obesity have failed to address the severity and prevalence of obesity, so alternative approaches based on nutritional and diet changes are attracting attention for the treatment of obesity. Fruit contains large amounts of simple sugars (glucose, fructose, sucrose, etc., which are well known to induce obesity. Thus, considering the amount of simple sugars found in fruit, it is reasonable to expect that their consumption should contribute to obesity rather than weight reduction. However, epidemiological research has consistently shown that most types of fruit have anti-obesity effects. Thus, due to their anti-obesity effects as well as their vitamin and mineral contents, health organizations are suggesting the consumption of fruit for weight reduction purposes. These contradictory characteristics of fruit with respect to human body weight management motivated us to study previous research to understand the contribution of different types of fruit to weight management. In this review article, we analyze and discuss the relationships between fruit and their anti-obesity effects based on numerous possible underlying mechanisms, and we conclude that each type of fruit has different effects on body weight.

  16. Role of the Gut Microbiome in the Pathogenesis of Obesity and Obesity-Related Metabolic Dysfunction

    NARCIS (Netherlands)

    Bouter, Kristien E.; van Raalte, Daniel H.; Groen, Albert K.; Nieuwdorp, Max

    The potential role of intestinal microbiota in the etiology of various human diseases has attracted massive attention in the last decade. As such, the intestinal microbiota has been advanced as an important contributor in the development of obesity and obesity-related metabolic dysfunctions, amongst

  17. Role of the Gut Microbiome in the Pathogenesis of Obesity and Obesity-Related Metabolic Dysfunction

    NARCIS (Netherlands)

    Bouter, Kristien E.; van Raalte, Daniël H.; Groen, Albert K.; Nieuwdorp, Max

    2017-01-01

    The potential role of intestinal microbiota in the etiology of various human diseases has attracted massive attention in the last decade. As such, the intestinal microbiota has been advanced as an important contributor in the development of obesity and obesity-related metabolic dysfunctions, amongst

  18. Lithium Chloride Dependent Glycogen Synthase Kinase 3 Inactivation Links Oxidative DNA Damage, Hypertrophy and Senescence in Human Articular Chondrocytes and Reproduces Chondrocyte Phenotype of Obese Osteoarthritis Patients.

    Directory of Open Access Journals (Sweden)

    Serena Guidotti

    Full Text Available Recent evidence suggests that GSK3 activity is chondroprotective in osteoarthritis (OA, but at the same time, its inactivation has been proposed as an anti-inflammatory therapeutic option. Here we evaluated the extent of GSK3β inactivation in vivo in OA knee cartilage and the molecular events downstream GSK3β inactivation in vitro to assess their contribution to cell senescence and hypertrophy.In vivo level of phosphorylated GSK3β was analyzed in cartilage and oxidative damage was assessed by 8-oxo-deoxyguanosine staining. The in vitro effects of GSK3β inactivation (using either LiCl or SB216763 were evaluated on proliferating primary human chondrocytes by combined confocal microscopy analysis of Mitotracker staining and reactive oxygen species (ROS production (2',7'-dichlorofluorescin diacetate staining. Downstream effects on DNA damage and senescence were investigated by western blot (γH2AX, GADD45β and p21, flow cytometric analysis of cell cycle and light scattering properties, quantitative assessment of senescence associated β galactosidase activity, and PAS staining.In vivo chondrocytes from obese OA patients showed higher levels of phosphorylated GSK3β, oxidative damage and expression of GADD45β and p21, in comparison with chondrocytes of nonobese OA patients. LiCl mediated GSK3β inactivation in vitro resulted in increased mitochondrial ROS production, responsible for reduced cell proliferation, S phase transient arrest, and increase in cell senescence, size and granularity. Collectively, western blot data supported the occurrence of a DNA damage response leading to cellular senescence with increase in γH2AX, GADD45β and p21. Moreover, LiCl boosted 8-oxo-dG staining, expression of IKKα and MMP-10.In articular chondrocytes, GSK3β activity is required for the maintenance of proliferative potential and phenotype. Conversely, GSK3β inactivation, although preserving chondrocyte survival, results in functional impairment via

  19. Obesity, adipokines, and lung disease.

    Science.gov (United States)

    Sood, Akshay

    2010-03-01

    This review summarizes the state of the current literature relating to the associations of lung disease on obesity and adipokines (proteins produced by adipose tissue) in humans. Obesity is an independent risk factor for asthma. Recent studies suggest that obesity is also an independent risk factor for chronic airflow obstruction, as is seen with chronic obstructive pulmonary disease (COPD). The mechanistic basis for these associations in humans is not established, although a possible role for adipokines has been invoked. Leptin, a proinflammatory adipokine, and adiponectin, an anti-inflammatory adipokine, are causally associated with asthma in mice. Although human studies are currently inconclusive, high-serum leptin and low-serum adiponectin concentrations predict asthma, independent of obesity, in select population groups, such as premenopausal women in the United States. In contradistinction, low-serum leptin and high-serum adiponectin concentrations are associated with stable COPD, although these associations are likely confounded by fat mass. Interestingly, leptin may promote systemic and airway inflammation in stable COPD patients. On the other hand, COPD may upregulate systemic and lung adiponectin expression. The precise mechanism and significance of the associations between these adipokines and lung disease at the current stage is confusing and frankly paradoxical in places. This area of research needs additional study that may open up novel therapeutic strategies for these lung diseases.

  20. Obesity, diabetes and leptin: lessons learned from obese hyperglycemic mice

    Directory of Open Access Journals (Sweden)

    Meftun Ahmed

    2008-07-01

    Full Text Available The recent epidemic nature of obesity and association of obesity with the development of type 2 diabetes demands dissection of the pathophysiology of this morbid disorder which is essential for better understanding of the process of evolution of insulin resistance. Different animal models have been used to explore the mechanism linking obesity to insulin resistance and type 2 diabetes. The discovery of ob gene and its product, leptin, has revealed the signaling system regulating energy balance in rodents. The mice lacking this ob gene, ob/ob mice, display obesity, hyperglycemia and hyperinsulinemia and has been extensively used for the study of type 2 diabetes and for potential drug development. In this review, the features and development of obese hyperglycemic syndrome, the role of leptin in the pathogenesis of the syndrome and finally the applicability of the findings in rodents to body weight regulation and pathogenesis of insulin resistance in humans have been summarized. Ibrahim Med. Coll. J. 2008; 2(2: 72-84

  1. Dissociation of GLP-1 and insulin association with food processing in the brain: GLP-1 sensitivity despite insulin resistance in obese humans

    Directory of Open Access Journals (Sweden)

    Martin Heni

    2015-12-01

    Conclusions: The postprandial release of GLP-1 might alter reward processes in the orbitofrontal cortex and might thereby support the termination of food intake and reduce hunger. While obese persons showed brain insulin resistance, no GLP-1 resistance was observed. Our study provides novel insight into the central regulation of food intake by the incretin hormone GLP-1.

  2. Reduced Systemic Levels of IL-10 Are Associated with the Severity of Obstructive Sleep Apnea and Insulin Resistance in Morbidly Obese Humans

    Directory of Open Access Journals (Sweden)

    Sonia Leon-Cabrera

    2015-01-01

    Full Text Available Obstructive sleep apnea (OSA has been related to elevation of inflammatory cytokines and development of insulin resistance in morbidly obese (MO subjects. However, it is still unclear whether the systemic concentration of anti-inflammatory mediators is also affected in MO subjects directly related to the severity of OSA and level of insulin resistance. Normal weight and MO subjects were subjected to overnight polysomnography in order to establish the severity of OSA, according to the apnea-hypopnea index (AHI. Blood samples were obtained for estimation of total cholesterol and triglycerides, insulin, glucose, insulin resistance, tumor necrosis factor alpha (TNF-α, interleukin 12 (IL12, and interleukin 10 (IL-10. Serum levels of IL-10 were significantly lower in MO subjects with OSA than in MO and control individuals without OSA. Besides being inversely associated with serum TNF-α and IL-12, decreased IL-10 levels were significantly related to increased AHI, hyperinsulinemia, and insulin resistance. Serum IL-10 is significantly reduced in morbidly obese subjects with severe OSA while also showing a clear relationship with a state of hyperinsulinemia and insulin resistance probably regardless of obesity in the present sample. It may be of potential clinical interest to identify the stimulatory mechanisms of IL-10 in obese individuals with OSA.

  3. Effects of exercise training and diet on lipid kinetics during free fatty acid-induced insulin resistance in older obese humans with impaired glucose tolerance

    DEFF Research Database (Denmark)

    Solomon, Thomas; Haus, Jacob M; Marchetti, Christine M

    2009-01-01

    the effect of 12 wk of exercise training with and without caloric restriction on FFA turnover and oxidation (FFA(ox)) during acute FFA-induced insulin resistance. Sixteen obese subjects with impaired glucose tolerance were randomized to either a hypocaloric (n = 8; -598 +/- 125 kcal/day, 66 +/- 1 yr, 32...

  4. The snacking rat as model of human obesity: effects of a free-choice high-fat high-sugar diet on meal patterns

    NARCIS (Netherlands)

    La Fleur, S. E.; Luijendijk, M. C. M.; van der Zwaal, E. M.; Brans, M. A. D.; Adan, R. A. H.

    2014-01-01

    Rats subjected to a free-choice high-fat high-sugar (fcHFHS) diet persistently overeat, exhibit increased food-motivated behavior and become overtly obese. Conversely, several studies using a non-choice (nc) high-energy diet showed only an initial increase in food intake with unaltered or reduced

  5. Utilizing health records to characterize obesity, comorbidities, and health-care services in one human service agency in the United States.

    Science.gov (United States)

    Fisher, Kathleen; Hardie, Thomas L; Ranjan, Sobhana; Peterson, Justin

    2017-12-01

    US surveys report higher prevalence of obesity in adults with intellectual disability. Health records of 40 adults with intellectual disability were retrospectively reviewed for data on health status, problem lists with International Classification of Diseases, Ninth Revision codes, medication lists, and health encounters over 18 months. Mean age was 49.5 years, 53% were males. Prevalence of overweight, obese, and morbidly obese was 28%, 58%, and 23%, respectively. Primary diagnosis was intellectual disability (50% mild, 33% moderate, 10% severe, and 8% profound), 85% had mental health disorders (67.5% with affective or mood and 42.5% had anxiety disorders). On average, residents consumed 2.63 psychotropic medications daily with additional 5.75 medications for axis 3 diagnoses and made 39.2 health visits over past 18 months. Our analysis supports increased prevalence of overweight/obesity, higher comorbidities, dual psychiatric diagnosis, substantial medication consumption, and higher utilization of health-care services in adults with intellectual disabilities. Targeted health interventions are therefore essential to improve their health and quality of life.

  6. Obesity and dermatology.

    Science.gov (United States)

    Scheinfeld, Noah S

    2004-01-01

    Obesity is associated with a number of dermatoses. It affects cutaneous sensation, temperature regulation, foot shape, and vasculature. Acanthosis nigricans is the most common dermatological manifestation of obesity. Skin tags are more commonly associated with diabetes than with obesity. Obesity increases the incidence of cutaneous infections that include: candidiasis, intertigo, candida folliculitis, furunculosis, erythrasma, tinea cruris, and folliculitis. Less common infections include cellulitis, necrotizing fasciitis, and gas gangrene. Leg ulcerations, lymphedema, plantar hyperkeratosis, and striae are more common with obesity. Hormonal abnormalities and genetic syndromes (Prader-Willi) are related to obesity and its dermatoses; however, cellulite is not related to obesity.

  7. Chronodisruption and Obesity

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2015-12-01

    Full Text Available BACKGROUND: Attempts to understand the causes of obesity and develop new therapeutic strategies have mostly focused on caloric intake and energy expenditure. Recent studies have shown that the circadian clock controls energy homeostasis by regulating circadian expression and/or activity of enzymes, hormones, and transport systems involved in metabolism. Moreover, disruption of circadian rhythms leads to obesity and metabolic disorders. CONTENT:Regularly alternating periods of light and darkness, such as normally occur with the rising and the setting of the sun, are essential for the maintenance of undisturbed circadian rhythms in all organisms including humans. The light-dark environment, as detected by specialized photoreceptors in the retinas, impacts the endogenous circadian clock in the anterior hypothalamus, the suprachiasmatic nuclei. These nuclei, via both neural and humoral signals, communicate with cells throughout the organism to establish regular circadian rhythms. The introduction of artificial sources of light roughly 150 years ago has significantly undermined the naturally occurring light-dark environment and, likewise, has disturbed circadian rhythms since light is now available at unusual times, i.e., at night. Light at night is known to cause circadian disruption and melatonin suppression. Many potentially pathophysiological consequences of these artificial light-mediated changes, include cancer, cardiovascular diseases, insomnia, metabolic syndrome, diabetes, and cognitive disorders may be aggravated by the increased exposure to light at night, which is inevitable in well-developed societies that have undergone extensive electrification. SUMMARY: Therefore, it is plausible that resetting of the circadian clock can be used as a new approach to attenuate obesity. Feeding regimens, such as restricted feeding, calorie restriction and intermittent fasting, provide a time cue and reset the circadian clock and

  8. Psychological perspectives in obesity

    OpenAIRE

    Roldus Andy Bunga

    2018-01-01

    Abstract Obesity has become a leading public health concern. Over 1 billion people are now overweight or obese, and the prevalence of these conditions is rising rapidly. Psychological aspects of obesity are so important, psychological assessments and interventions have become an integral part of a multidisciplinary approach to treating obesity. Multiple environmental, genetic, neuro-endocrinological, and psychosocial factors contribute to the development of obesity. Though there are many d...

  9. Future of obesity prevention and treatment.

    Science.gov (United States)

    Ness-Abramof, Rosane; Apovian, Caroline M

    2009-01-01

    The prevalence of obesity has risen sharply during the last 4 decades imposing a serious health burden to modern society. Obesity is known to cause and exacerbate many chronic diseases such as diabetes, hypertension, dyslipidemia, coronary heart disease, stroke, obstructive sleep apnea and certain cancers, among many others. The rise in obesity prevalence is mainly caused by overconsumption of energy, coupled to a sedentary life in susceptible individuals. Weight homeostasis is paramount for survival and its control is coordinated by neural and endocrine signals emanating from the fat tissue, digestive system and brain. During thousands of years humans were challenged by nutrient deprivation, developing an efficient mechanism to store energy. It explains the difficulty in losing weight, making obesity prevention the main effective health approach to halt the obesity epidemic.

  10. Obesity as disruptor of the female fertility.

    Science.gov (United States)

    Silvestris, Erica; de Pergola, Giovanni; Rosania, Raffaele; Loverro, Giuseppe

    2018-03-09

    Both obesity and overweight are increasing worldwide and have detrimental influences on several human body functions including the reproductive health. In particular, obese women undergo perturbations of the 'hypothalamic pituitary ovarian axis', and frequently suffer of menstrual dysfunction leading to anovulation and infertility. Besides the hormone disorders and subfertility that are common in the polycystic ovary syndrome (PCOS), in obesity the adipocytes act as endocrine organ. The adipose tissue indeed, releases a number of bioactive molecules, namely adipokines, that variably interact with multiple molecular pathways of insulin resistance, inflammation, hypertension, cardiovascular risk, coagulation, and oocyte differentiation and maturation. Moreover, endometrial implantation and other reproductive functions are affected in obese women with complications including delayed conceptions, increased miscarriage rate, reduced outcomes in assisted conception treatments.On the contrary, weight loss programs through lifestyle modification in obese women, have been proven to restore menstrual cyclicity and ovulation and improve the likelihood of conception.

  11. Melanocortin 4 receptor mutations in obese Czech children

    DEFF Research Database (Denmark)

    Hainerová, Irena; Larsen, Lesli H; Holst, Birgitte

    2007-01-01

    Mutations in the melanocortin 4 receptor gene (MC4R) represent the most common known cause of monogenic human obesity.......Mutations in the melanocortin 4 receptor gene (MC4R) represent the most common known cause of monogenic human obesity....

  12. The Role of the Gut Microbiota in Childhood Obesity

    DEFF Research Database (Denmark)

    Pihl, Andreas Friis; Fonvig, Cilius Esmann; Stjernholm, Theresa

    2016-01-01

    BACKGROUND: Childhood and adolescent obesity has reached epidemic proportions worldwide. The pathogenesis of obesity is complex and multifactorial, in which genetic and environmental contributions seem important. The gut microbiota is increasingly documented to be involved in the dysmetabolism...... component of the human gut microbiota in childhood and adolescent-onset obesity, with a special focus on the factors involved in the early development of the gut bacterial ecosystem, and how modulation of this microbial community might serve as a basis for new therapeutic strategies in combating childhood...... the role of the gut microbiota in the development of childhood obesity may potentially reveal new strategies for obesity prevention and treatment....

  13. Assessment of obesity in pigtailed monkeys (Macaca nemestrina).

    Science.gov (United States)

    Walike, B C; Goodner, C J; Koerker, D J; Chideckel, E W; Kalnasy, L W

    1977-01-01

    Obesity was studied in a colony of 873 Macaca nemestrina to establish tools for epidemiologic studies, to examine a genetic form of obesity, to document age/sex relationships to obesity, and to compare metabolic profiles of obese and normal monkeys. Age/weight growth curves were analyzed to select the most obese monkeys and age- and sex-matched normal controls. Degree of adiposity was determined using tritiated water for estimation of lean body mass. Body weight, anterior trunk height, and abdominal and triceps skinfolds were measured. Fasting insulin, fasting free fatty acids, and glucose disappearance rate were determined. The results give evidence of similarities between macaque and human obestiy.

  14. Plasma sphingosine-1-phosphate is elevated in obesity.

    Directory of Open Access Journals (Sweden)

    Greg M Kowalski

    Full Text Available BACKGROUND: Dysfunctional lipid metabolism is a hallmark of obesity and insulin resistance and a risk factor for various cardiovascular and metabolic complications. In addition to the well known increase in plasma triglycerides and free fatty acids, recent work in humans and rodents has shown that obesity is associated with elevations in the bioactive class of sphingolipids known as ceramides. However, in obesity little is known about the plasma concentrations of sphinogsine-1-phosphate (S1P, the breakdown product of ceramide, which is an important signaling molecule in mammalian biology. Therefore, the purpose of this study was to examine the impact of obesity on circulating S1P concentration and its relationship with markers of glucose metabolism and insulin sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: Plasma S1P levels were determined in high-fat diet (HFD-induced and genetically obese (ob/ob mice along with obese humans. Circulating S1P was elevated in both obese mouse models and in obese humans compared with lean healthy controls. Furthermore, in humans, plasma S1P positively correlated with total body fat percentage, body mass index (BMI, waist circumference, fasting insulin, HOMA-IR, HbA1c (%, total and LDL cholesterol. In addition, fasting increased plasma S1P levels in lean healthy mice. CONCLUSION: We show that elevations in plasma S1P are a feature of both human and rodent obesity and correlate with metabolic abnormalities such as adiposity and insulin resistance.

  15. Effects of Probiotics and Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Review of Human Clinical Trials

    OpenAIRE

    S?ez-Lara, Maria Jose; Robles-Sanchez, Candido; Ruiz-Ojeda, Francisco Javier; Plaza-Diaz, Julio; Gil, Angel

    2016-01-01

    The use of probiotics and synbiotics in the prevention and treatment of different disorders has dramatically increased over the last decade. Both probiotics and synbiotics are well known ingredients of functional foods and nutraceuticals and may provide beneficial health effects because they can influence the intestinal microbial ecology and immunity. The present study reviews the effects of probiotics and synbiotics on obesity, insulin resistance syndrome (IRS), type 2 diabetes (T2D) and non...

  16. Sleep and Obesity: A focus on animal models

    Science.gov (United States)

    Mavanji, Vijayakumar; Billington, Charles J.; Kotz, Catherine M.; Teske, Jennifer A.

    2012-01-01

    The rapid rise in obesity prevalence in the modern world parallels a significant reduction in restorative sleep (Agras et al., 2004; Dixon et al., 2007; Dixon et al., 2001; Gangwisch and Heymsfield, 2004; Gupta et al., 2002; Sekine et al., 2002; Vioque et al., 2000; Wolk et al., 2003). Reduced sleep time and quality increases the risk for obesity, but the underlying mechanisms remain unclear (Gangwisch et al., 2005; Hicks et al., 1986; Imaki et al., 2002; Jennings et al., 2007; Moreno et al., 2006). A majority of the theories linking human sleep disturbances and obesity rely on self-reported sleep. However, studies with objective measurements of sleep/wake parameters suggest a U-shaped relationship between sleep and obesity. Studies in animal models are needed to improve our understanding of the association between sleep disturbances and obesity. Genetic and experimenter-induced models mimicking characteristics of human obesity are now available and these animal models will be useful in understanding whether sleep disturbances determine propensity for obesity, or result from obesity. These models exhibit weight gain profiles consistently different from control animals. Thus a careful evaluation of animal models will provide insight into the relationship between sleep disturbances and obesity in humans. In this review we first briefly consider the fundamentals of sleep and key sleep disturbances, such as sleep fragmentation and excessive daytime sleepiness (EDS), observed in obese individuals. Then we consider sleep deprivation studies and the role of circadian alterations in obesity. We describe sleep/wake changes in various rodent models of obesity and obesity resistance. Finally, we discuss possible mechanisms linking sleep disturbances with obesity. PMID:22266350

  17. Obesity: A Venusian story of Paleolithic proportions

    Directory of Open Access Journals (Sweden)

    Krishna G Seshadri

    2012-01-01

    Full Text Available Art through the ages has been a marker of societal trends and fashion. Obesity is proscribed by physicians and almost reviled by today′s society. While Venus (Aphrodite continues to be the role model for those to aspire to free themselves from the clutches of obesity, Paleolithic humans had a different view of the perfect female form. Whether the Venus of Willendorf was a fashion symbol will be never answered, but the fact is that she remains testimony to the fact that obesity has been with us for several millennia.

  18. Obesity Stigma and Bias.

    Science.gov (United States)

    Fruh, Sharon M; Nadglowski, Joe; Hall, Heather R; Davis, Sara L; Crook, Errol D; Zlomke, Kimberly

    2016-01-01

    Overweight and obesity are escalating in epidemic proportions in the United States. Individuals with overweight and obesity are often reluctant to seek medical help, not only for weight reduction but also for any health issue because of perceived provider discrimination. Providers who are biased against individuals with obesity can hinder our nation's effort to effectively fight the obesity epidemic. By addressing weight bias in the provider setting, individuals affected by obesity may be more likely to engage in a meaningful and productive discussion of weight. Providers need to be the go-to source for obesity-focused information on new and emerging treatments.

  19. Effects of testosterone supplementation on whole body and regional fat mass and distribution in human immunodeficiency virus-infected men with abdominal obesity.

    Science.gov (United States)

    Bhasin, Shalender; Parker, Robert A; Sattler, Fred; Haubrich, Richard; Alston, Beverly; Umbleja, Triin; Shikuma, Cecilia M

    2007-03-01

    Whole body and abdominal obesity are associated with increased risk of diabetes mellitus and heart disease. The effects of testosterone therapy on whole body and visceral fat mass in HIV-infected men with abdominal obesity are unknown. The objective of this study was to determine the effects of testosterone therapy on intraabdominal fat mass and whole body fat distribution in HIV-infected men with abdominal obesity. IN this multicenter, randomized, placebo-controlled, double-blind trial, 88 HIV-positive men with abdominal obesity (waist-to-hip ratio > 0.95 or mid-waist circumference > 100 cm) and total testosterone 125-400 ng/dl, or bioavailable testosterone less than 115 ng/dl, or free testosterone less than 50 pg/ml on stable antiretroviral regimen, and HIV RNA less than 10,000 copies per milliliter were randomized to receive 10 g testosterone gel or placebo daily for 24 wk. Fat mass and distribution were determined by abdominal computerized tomography and dual energy x-ray absorptiometry during wk 0, 12, and 24. We used an intention-to-treat approach and nonparametric statistical methods. Baseline characteristics were balanced between groups. In 75 subjects evaluated, median percent change from baseline to wk 24 in visceral fat did not differ significantly between groups (testosterone 0.3%, placebo 3.1%, P = 0.75). Total (testosterone -1.5%, placebo 4.3%, P = 0.04) and sc (testosterone-7.2%, placebo 8.1%, P fat mass decreased in testosterone-treated men, but increased in placebo group. Testosterone therapy was associated with significant decrease in whole body, trunk, and appendicular fat mass by dual energy x-ray absorptiometry (all P fat increased significantly in the placebo group. The percent of individuals reporting a decrease in abdomen (P = 0.01), neck (P = 0.08), and breast size (P = 0.01) at wk 24 was significantly greater in testosterone-treated than placebo-treated men. Testosterone-treated men had greater increase in lean body mass than placebo

  20. High-fat diet and maternal obesity-associated epigenetic regulation of bone development

    Science.gov (United States)

    Due to the worldwide epidemic in obesity, maternal obesity has recently seen an explosion in investigations in both animal models and humans on its effects on offspring phenotype and pathologies including diabetes, hyperlipidemia, cardiovascular disease, and cancer. Epigenetic mechanisms presumably ...

  1. Endocrine Disruptors and Obesity.

    Science.gov (United States)

    Darbre, Philippa D

    2017-03-01

    The purpose of this review was to summarise current evidence that some environmental chemicals may be able to interfere in the endocrine regulation of energy metabolism and adipose tissue structure. Recent findings demonstrate that such endocrine-disrupting chemicals, termed "obesogens", can promote adipogenesis and cause weight gain. This includes compounds to which the human population is exposed in daily life through their use in pesticides/herbicides, industrial and household products, plastics, detergents, flame retardants and as ingredients in personal care products. Animal models and epidemiological studies have shown that an especially sensitive time for exposure is in utero or the neonatal period. In summarising the actions of obesogens, it is noteworthy that as their structures are mainly lipophilic, their ability to increase fat deposition has the added consequence of increasing the capacity for their own retention. This has the potential for a vicious spiral not only of increasing obesity but also increasing the retention of other lipophilic pollutant chemicals with an even broader range of adverse actions. This might offer an explanation as to why obesity is an underlying risk factor for so many diseases including cancer.

  2. Immunometabolism in obese asthmatics: are we there yet?

    Science.gov (United States)

    Periyalil, Hashim A; Gibson, Peter G; Wood, Lisa G

    2013-09-10

    Obesity is now recognised as a worldwide epidemic. The recent International Association for the Study of Obesity/International Obesity Taskforce (IASO/IOTF) analysis estimates that approximately 1.0 billion adults are currently overweight and a further 475 million are obese. Obesity has huge psychosocial impact with obese children and adolescents facing discrimination and stigmatization in many areas of their lives leading to body dissatisfaction, low self-esteem and depression. Indeed, obesity is recognised as an important risk factor for the development of several chronic diseases such as hypertension, cancer, asthma and metabolic syndrome. Chronic low grade systemic inflammation is considered as a hallmark of obesity and may possibly explain the link between obesity and chronic disease, in particular the increased incidence, prevalence and severity of asthma in obese individuals. There is now strong evidence for infiltration of immune and inflammatory cells into adipose tissue that drives systemic inflammation and subsequent end organ damage. In addition to adipocytes, the key adipose tissue resident immune cells are macrophages and mast cells. Immunometabolism, as an emerging field of investigation, explores the pivotal role of these immune cells in translating immunological changes to metabolic effects in obesity. Abundance of free fatty acids, along with other inflammatory cytokines shift the balance of metabolic homeostasis to pro-inflammatory status by influencing the development of inflammatory cell lineage, which, further exhibits distinct functional phenotypes. There is emerging evidence for macrophage activation and functional polarization of an anti-inflammatory M2 phenotype towards a pro-inflammatory M1 phenotype of macrophages in obese adipose tissue. Similarly, studies in both obese humans and murine models reveal the pathognomic presence of an increased number of mast cells in visceral adipose tissue. These suggest a possible contribution of mast

  3. Immunometabolism in Obese Asthmatics: Are We There Yet?

    Directory of Open Access Journals (Sweden)

    Lisa G. Wood

    2013-09-01

    Full Text Available Obesity is now recognised as a worldwide epidemic. The recent International Association for the Study of Obesity/International Obesity Taskforce (IASO/IOTF analysis estimates that approximately 1.0 billion adults are currently overweight and a further 475 million are obese. Obesity has huge psychosocial impact with obese children and adolescents facing discrimination and stigmatization in many areas of their lives leading to body dissatisfaction, low self-esteem and depression. Indeed, obesity is recognised as an important risk factor for the development of several chronic diseases such as hypertension, cancer, asthma and metabolic syndrome. Chronic low grade systemic inflammation is considered as a hallmark of obesity and may possibly explain the link between obesity and chronic disease, in particular the increased incidence, prevalence and severity of asthma in obese individuals. There is now strong evidence for infiltration of immune and inflammatory cells into adipose tissue that drives systemic inflammation and subsequent end organ damage. In addition to adipocytes, the key adipose tissue resident immune cells are macrophages and mast cells. Immunometabolism, as an emerging field of investigation, explores the pivotal role of these immune cells in translating immunological changes to metabolic effects in obesity. Abundance of free fatty acids, along with other inflammatory cytokines shift the balance of metabolic homeostasis to pro-inflammatory status by influencing the development of inflammatory cell lineage, which, further exhibits distinct functional phenotypes. There is emerging evidence for macrophage activation and functional polarization of an anti-inflammatory M2 phenotype towards a pro-inflammatory M1 phenotype of macrophages in obese adipose tissue. Similarly, studies in both obese humans and murine models reveal the pathognomic presence of an increased number of mast cells in visceral adipose tissue. These suggest a possible

  4. Transcriptomic identification of ADH1B as a novel candidate gene for obesity and insulin resistance in human adipose tissue in Mexican Americans from the Veterans Administration Genetic Epidemiology Study (VAGES.

    Directory of Open Access Journals (Sweden)

    Deidre A Winnier

    Full Text Available Type 2 diabetes (T2D is a complex metabolic disease that is more prevalent in ethnic groups such as Mexican Americans, and is strongly associated with the risk factors obesity and insulin resistance. The goal of this study was to perform whole genome gene expression profiling in adipose tissue to detect common patterns of gene regulation associated with obesity and insulin resistance. We used phenotypic and genotypic data from 308 Mexican American participants from the Veterans Administration Genetic Epidemiology Study (VAGES. Basal fasting RNA was extracted from adipose tissue biopsies from a subset of 75 unrelated individuals, and gene expression data generated on the Illumina BeadArray platform. The number of gene probes with significant expression above baseline was approximately 31,000. We performed multiple regression analysis of all probes with 15 metabolic traits. Adipose tissue had 3,012 genes significantly associated with the traits of interest (false discovery rate, FDR ≤ 0.05. The significance of gene expression changes was used to select 52 genes with significant (FDR ≤ 10(-4 gene expression changes across multiple traits. Gene sets/Pathways analysis identified one gene, alcohol dehydrogenase 1B (ADH1B that was significantly enriched (P < 10(-60 as a prime candidate for involvement in multiple relevant metabolic pathways. Illumina BeadChip derived ADH1B expression data was consistent with quantitative real time PCR data. We observed significant inverse correlations with waist circumference (2.8 x 10(-9, BMI (5.4 x 10(-6, and fasting plasma insulin (P < 0.001. These findings are consistent with a central role for ADH1B in obesity and insulin resistance and provide evidence for a novel genetic regulatory mechanism for human metabolic diseases related to these traits.

  5. Core body temperature in obesity.

    Science.gov (United States)

    Heikens, Marc J; Gorbach, Alexander M; Eden, Henry S; Savastano, David M; Chen, Kong Y; Skarulis, Monica C; Yanovski, Jack A

    2011-05-01

    A lower core body temperature set point has been suggested to be a factor that could potentially predispose humans to develop obesity. We tested the hypothesis that obese individuals have lower core temperatures than those in normal-weight individuals. In study 1, nonobese [body mass index (BMI; in kg/m(2)) temperature-sensing capsules, and we measured core temperatures continuously for 24 h. In study 2, normal-weight (BMI of 18-25) and obese subjects swallowed temperature-sensing capsules to measure core temperatures continuously for ≥48 h and kept activity logs. We constructed daily, 24-h core temperature profiles for analysis. Mean (±SE) daily core body temperature did not differ significantly between the 35 nonobese and 46 obese subjects (36.92 ± 0.03°C compared with 36.89 ± 0.03°C; P = 0.44). Core temperature 24-h profiles did not differ significantly between 11 normal-weight and 19 obese subjects (P = 0.274). Women had a mean core body temperature ≈0.23°C greater than that of men (36.99 ± 0.03°C compared with 36.76 ± 0.03°C; P body temperature. It may be necessary to study individuals with function-altering mutations in core temperature-regulating genes to determine whether differences in the core body temperature set point affect the regulation of human body weight. These trials were registered at clinicaltrials.gov as NCT00428987 and NCT00266500.

  6. Gut Microbiome and Obesity: A Plausible Explanation for Obesity.

    Science.gov (United States)

    Sanmiguel, Claudia; Gupta, Arpana; Mayer, Emeran A

    2015-06-01

    Obesity is a multifactorial disorder that results in excessive accumulation of adipose tissue. Although obesity is caused by alterations in the energy consumption/expenditure balance, the factors promoting this disequilibrium are incompletely understood. The rapid development of new technologies and analysis strategies to decode the gut microbiota composition and metabolic pathways has opened a door into the complexity of the guest-host interactions between the gut microbiota and its human host in health and in disease. Pivotal studies have demonstrated that manipulation of the gut microbiota and its metabolic pathways can affect host's adiposity and metabolism. These observations have paved the way for further assessment of the mechanisms underlying these changes. In this review we summarize the current evidence for possible mechanisms underlying gut microbiota induced obesity. The review addresses some well-known effects of the gut microbiota on energy harvesting and changes in metabolic machinery, on metabolic and immune interactions and on possible changes in brain function and behavior. Although there is limited understanding on the symbiotic relationship between us and our gut microbiome, and how disturbances of this relationship affects our health, there is compelling evidence for an important role of the gut microbiota in the development and perpetuation of obesity.

  7. Gut Microbiome and Obesity: A Plausible Explanation for Obesity

    Science.gov (United States)

    Sanmiguel, Claudia; Gupta, Arpana; Mayer, Emeran A.

    2015-01-01

    Obesity is a multifactorial disorder that results in excessive accumulation of adipose tissue. Although obesity is caused by alterations in the energy consumption/expenditure balance, the factors promoting this disequilibrium are incompletely understood. The rapid development of new technologies and analysis strategies to decode the gut microbiota composition and metabolic pathways has opened a door into the complexity of the guest-host interactions between the gut microbiota and its human host in health and in disease. Pivotal studies have demonstrated that manipulation of the gut microbiota and its metabolic pathways can affect host’s adiposity and metabolism. These observations have paved the way for further assessment of the mechanisms underlying these changes. In this review we summarize the current evidence for possible mechanisms underlying gut microbiota induced obesity. The review addresses some well-known effects of the gut microbiota on energy harvesting and changes in metabolic machinery, on metabolic and immune interactions and on possible changes in brain function and behavior. Although there is limited understanding on the symbiotic relationship between us and our gut microbiome, and how disturbances of this relationship affects our health, there is compelling evidence for an important role of the gut microbiota in the development and perpetuation of obesity. PMID:26029487

  8. Obesity: Pathophysiology and Intervention

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    2014-11-01

    Full Text Available Obesity presents a major health hazard of the 21st century. It promotes co-morbid diseases such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Excessive energy intake, physical inactivity, and genetic susceptibility are main causal factors for obesity, while gene mutations, endocrine disorders, medication, or psychiatric illnesses may be underlying causes in some cases. The development and maintenance of obesity may involve central pathophysiological mechanisms such as impaired brain circuit regulation and neuroendocrine hormone dysfunction. Dieting and physical exercise offer the mainstays of obesity treatment, and anti-obesity drugs may be taken in conjunction to reduce appetite or fat absorption. Bariatric surgeries may be performed in overtly obese patients to lessen stomach volume and nutrient absorption, and induce faster satiety. This review provides a summary of literature on the pathophysiological studies of obesity and discusses relevant therapeutic strategies for managing obesity.

  9. Obesity and government.

    Science.gov (United States)

    Kahan, Scott; Zvenyach, Tracy

    2016-10-01

    Despite much effort, obesity prevalence and disease severity continues to worsen. The purpose of this review is to describe the leading government supported food and nutrition interventions and policies to prevent and address obesity in the USA. The review also summarizes obesity interventions and policies that the government plays a role in, but further development is warranted. The government's role in obesity has largely focused on interventions and policies such as national surveillance, obesity education and awareness, grant-based food subsidy programs, zoning for food access, school-based nutrition programs, dietary guidelines, nutrition labeling, and food marketing and pricing policies. The government has played a lesser role in obesity interventions and policies that provide access to evidence-based obesity care to people affected by the disease. Given the magnitude of the obesity epidemic, the government should explore multiple evidence-based interventions and policies across prevention and clinical care.

  10. Overweight and Obesity Statistics

    Science.gov (United States)

    ... of young children were considered to have extreme obesity. Among children and youth ages 6 to 11, about 1 ... Children and Adolescents 3,5 The prevalence of obesity among children and adolescents 2 to 19 years increased between ...

  11. Defining Overweight and Obesity

    Science.gov (United States)

    ... Micronutrient Malnutrition State and Local Programs Defining Adult Overweight and Obesity Recommend on Facebook Tweet Share Compartir ... weight for a given height is described as overweight or obese. Body Mass Index, or BMI, is ...

  12. Personality Characteristics And Obesity

    Directory of Open Access Journals (Sweden)

    Asthana Sunita

    1999-01-01

    Full Text Available Research question: Whether certain personality characteristics of obese women make them prone towards psychological problem? Objective: To assess certain personality characteristics of obese women. Study design: Cross-sectional community based study. Setting: Affluent localities of Varanasi city. Participants: Women above 15 years of age. Statistical Analysis: Mean, S.D and ‘t’ test. Results: On 16 PF scale obese women were found more reserved, critical, depressed, worried and troubled than the non-obese women. Obese also manifested subsequently less felling of contentment, happiness satisfaction with life experiences, low sense of achievement on PGI Well-Being. Obese women showed more distress and apprehension over their negative evaluation and distressed with day to day Conclusion: Obese women evidenced significantly more neurotic than non- obese women.

  13. Childhood obesity. Treatment options.

    Science.gov (United States)

    Steinbeck, Katharine

    2005-09-01

    The prevalence of child and adolescent overweight and obesity is rapidly increasing and is associated with morbidity, both medical and psychosocial. Obesity is unlikely to resolve spontaneously. It is important that health professionals can assess obesity and initiate an action plan. The evidence base for what works best in the management of child and adolescent overweight and obesity is limited. It is uncertain whether protocols from clinical research trials can be translated into primary care. Dietary change, with an emphasis on lower fat intake and smaller portion size, should be commenced. There should be an increase in physical activity and a decrease in sedentary behaviours, combined with behavioural change and parental involvement. These are the elements of a lifestyle intervention. In the severely obese adolescent with obesity-related co-morbidity, the use of very low-energy diets and anti-obesity agents could be considered. Bariatric surgery may be indicated in carefully selected, older, severely obese adolescents.

  14. Obesity hypoventilation syndrome (OHS)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000085.htm Obesity hypoventilation syndrome (OHS) To use the sharing features on this page, please enable JavaScript. Obesity hypoventilation syndrome (OHS) is a condition in some ...

  15. Obesity and health (image)

    Science.gov (United States)

    Obesity increases a person's risk of illness and death due to diabetes, stroke, heart disease, hypertension, high cholesterol, and kidney and gallbladder disease. Obesity may increase the risk for some types of ...

  16. [Epidemiology of obesity].

    Science.gov (United States)

    Möhr, M

    1977-05-15

    In the GDR about 20% of the males and 40% of the females were estimated to be obese. In the country obesity is more spread than in the town. Increased disablement of obese persons leads to reduction of the national income. With higher expenses for nutrition the frequency of obestiy increases. Hypophages and hyperphages are differently distributed in persons with normal weight and obese ones, so that the average establishments do not reflect the differentiated situation in nutrition. Obesity correlates with the type of structure; with increasing obesity dominate pyknomorphous tendencies of growth. Also in normal weight pyknomorphous persons have a higher proportion of fat. We should speak of obesity in such a case, when, taking into consideration biological differentiations, the normal proportion of the fat in the body is increased by more than 1/3. For epidemiological serial examinations the degrees of relative weight basing on optimum weight are a favourable basis for the classification of obesity.

  17. Disability and Obesity

    Science.gov (United States)

    ... About Us Information For… Media Policy Makers CDC Employees and Reasonable Accommodations (RA) Disability and Obesity Language: English (US) Español (Spanish) Recommend on Facebook Tweet Share Compartir Overweight and obesity are both ...

  18. Allegheny County Obesity Rates

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — Obesity rates for each Census Tract in Allegheny County were produced for the study “Developing small-area predictions for smoking and obesity prevalence in the...

  19. OPEN about obesity

    DEFF Research Database (Denmark)

    Lissner, L; Troiano, R P; Midthune, D

    2007-01-01

    frequency questionnaires (FFQ), doubly labelled water (DLW) and urinary nitrogen (UN) assessments. RESULTS: In obese and non-obese subgroups, FFQ yielded lower energy and protein intake estimates than 24HR, although biomarker-based information indicated under-reporting with both dietary instruments. Gender...... differences in obesity-related bias were noted. Among women, the DLW-based energy requirement was 378 kcal greater in obese than in non-obese groups; the FFQ was able to detect a statistically significant portion of this extra energy, while the 24HR was not. Among men, the DLW-based energy requirement was 485...... kcal greater in the obese group; however, neither FFQ nor 24HR detected this difference in energy requirement. Combining protein and energy estimates, obese men significantly over-reported the proportion of energy from protein using the 24HR, but not with the FFQ. In obese women, no significant...

  20. Ginseng and obesity

    Directory of Open Access Journals (Sweden)

    Zhipeng Li

    2018-01-01

    Full Text Available Although ginseng has been shown to have an antiobesity effect, antiobesity-related mechanisms are complex and have not been completely elucidated. In the present study, we evaluated ginseng’s effects on food intake, the digestion, and absorption systems, as well as liver, adipose tissue, and skeletal muscle in order to identify the mechanisms involved. A review of previous in vitro and in vivo studies revealed that ginseng and ginsenosides can increase energy expenditure by stimulating the adenosine monophosphate-activated kinase pathway and can reduce energy intake. Moreover, in high fat diet-induced obese and diabetic individuals, ginseng has shown a two-way adjustment effect on adipogenesis. Nevertheless, most of the previous studies into antiobesity effects of ginseng have been animal based, and there is a paucity of evidence supporting the suggestion that ginseng can exert an antiobesity effect in humans.

  1. OSTEOARTHRITIS AND OBESITY

    Directory of Open Access Journals (Sweden)

    E. A. Strebkova

    2015-01-01

    Full Text Available The review highlights the impact of obesity on the development, progression, and severity of osteoarthritis (OA and discusses treatments for obesity in this disease. Weight loss in obese patients with OA is shown to lead to a reduction in clinical manifestations. Despite a great deal of performed investigations of the impact of non-drug therapy for obesity (diet, physical activity, their results are contradictory and call for further investigation

  2. Anesthetizing the obese child

    DEFF Research Database (Denmark)

    Mortensen, Anette; Lenz, Katja; Abildstrøm, Hanne

    2011-01-01

    The prevalence of childhood obesity is increasing. The focus of this review is the special anesthetic considerations regarding the perioperative management of obese children. With obesity the risk of comorbidity such as asthma, obstructive sleep apnea, hypertension, and diabetes increases...... drugs. This has important implications on how to estimate the optimal drug dose. This article offers a review of the literature on definition, prevalence and the pathophysiology of childhood obesity and provides suggestions on preanesthetic evaluation, airway management and dosage of the anesthetic...

  3. Obesity and kidney disease

    OpenAIRE

    Silva Junior, Geraldo Bezerra da; Bentes, Ana Carla Sobral Novaes; Daher, Elizabeth De Francesco; Matos, Sheila Maria Alvim de

    2017-01-01

    Abstract Obesity has been pointed out as an important cause of kidney diseases. Due to its close association with diabetes and hypertension, excess weight and obesity are important risk factors for chronic kidney disease (CKD). Obesity influences CKD development, among other factors, because it predisposes to diabetic nephropathy, hypertensive nephrosclerosis and focal and segmental glomerulosclerosis. Excess weight and obesity are associated with hemodynamic, structural and histological rena...

  4. Economics and obesity policy.

    Science.gov (United States)

    Lusk, J L

    2017-06-01

    This paper elucidates the challenges surrounding the economics of some popular obesity-related policy proposals. Solid economic justifications for anti-obesity policies are often lacking, and evidence suggests policies like fat and soda taxes or restrictions on food stamp spending are unlikely to substantively affect obesity prevalence. In short, many of the same factors that make obesity such a complicated and multifaceted issue extend to the economic analysis of public health policies.

  5. Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis.

    LENUS (Irish Health Repository)

    Hogan, A E

    2011-11-01

    The innate immune cells, invariant natural killer T cells (iNKT cells), are implicated in the pathogenesis of psoriasis, an inflammatory condition associated with obesity and other metabolic diseases, such as diabetes and dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist. This was independent of change in glycaemic control. We proposed that this unexpected clinical outcome resulted from a direct effect of GLP-1 on iNKT cells.

  6. Childhood Obesity: An Overview

    Science.gov (United States)

    Reilly, John J.

    2007-01-01

    This article reviews recent research evidence, largely from systematic reviews, on a number of aspects of childhood obesity: its definition and prevalence; consequences; causes and prevention. The basis of the body mass index (BMI) as a means of defining obesity in children and adolescents is discussed: a high BMI for age constitutes obesity. In…

  7. Childhood environment and obesity

    Science.gov (United States)

    US children are at risk for developing childhood obesity. Currently, 23% of children ages 2–5 are overweight or obese, i.e., at or above the 85th percentile. This prevalence becomes even higher as children age, with 34% of children ages 6–11 being overweight or obese. Ethnic minority children are at...

  8. [Endocrine function in obesity].

    Science.gov (United States)

    Álvarez-Castro, Paula; Sangiao-Alvarellos, Susana; Brandón-Sandá, Iria; Cordido, Fernando

    2011-10-01

    Obesity is associated to significant disturbances in endocrine function. Hyper insulinemia and insulin resistance are the best known changes in obesity, but their mechanisms and clinical significance are not clearly established. Adipose tissue is considered to be a hormone-secreting endocrine organ; and increased leptin secretion from the adipocyte, a satiety signal, is a well-established endocrine change in obesity. In obesity there is a decreased GH secretion. Impairment of somatotropic function in obesity is functional and may be reversed in certain circumstances. The pathophysiological mechanism responsible for low GH secretion in obesity is probably multifactorial. There are many data suggesting that a chronic state of somatostatin hypersecretion results in inhibition of GH release. Increased FFA levels, as well as a deficient ghrelin secretion, probably contribute to the impaired GH secretion. In women, abdominal obesity is associated to hyperandrogenism and low sex hormone-binding globulin levels. Obese men, particularly those with morbid obesity, have decreased testosterone and gonadotropin levels. Obesity is associated to an increased cortisol production rate, which is compensated for by a higher cortisol clearance, resulting in plasma free cortisol levels that do not change when body weight increases. Ghrelin is the only known circulating orexigenic factor, and has been found to be decreased in obese people. In obesity there is also a trend to increased TSH and free T3 levels. Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.

  9. Childhood Obesity Facts

    Science.gov (United States)

    ... NCHS) data brief [PDF-705KB] The prevalence of obesity among children aged 2 to 5 years decreased significantly from ... 2292-9. Top of Page Prevalence of Childhood Obesity among Young Low-Income WIC Children in the United States, 2014 Obesity disproportionally affects ...

  10. Asthma and obesity

    DEFF Research Database (Denmark)

    Juel, Caroline Trunk-Black; Ali, Zarqa; Nilas, Lisbeth

    2012-01-01

    Obesity is a major health problem, and obesity is associated with a high incidence of asthma and poor asthma control. The aim of the present paper is to systematically review the current knowledge of the effect on overall asthma control of weight reduction in overweight and obese adults with asthma....

  11. Gut bacterial microbiota and obesity.

    Science.gov (United States)

    Million, M; Lagier, J-C; Yahav, D; Paul, M

    2013-04-01

    Although probiotics and antibiotics have been used for decades as growth promoters in animals, attention has only recently been drawn to the association between the gut microbiota composition, its manipulation, and obesity. Studies in mice have associated the phylum Firmicutes with obesity and the phylum Bacteroidetes with weight loss. Proposed mechanisms linking the microbiota to fat content and weight include differential effects of bacteria on the efficiency of energy extraction from the diet, and changes in host metabolism of absorbed calories. The independent effect of the microbiota on fat accumulation has been demonstrated in mice, where transplantation of microbiota from obese mice or mice fed western diets to lean or germ-free mice produced fat accumulation among recipients. The microbiota can be manipulated by prebiotics, probiotics, and antibiotics. Probiotics affect the microbiota directly by modulating its bacterial content, and indirectly through bacteriocins produced by the probiotic bacteria. Interestingly, certain probiotics are associated with weight gain both in animals and in humans. The effects are dependent on the probiotic strain, the host, and specific host characteristics, such as age and baseline nutritional status. Attention has recently been drawn to the association between antibiotic use and weight gain in children and adults. We herein review the studies describing the associations between the microbiota composition, its manipulation, and obesity. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

  12. Locus of Control and Obesity

    Directory of Open Access Journals (Sweden)

    Florence eNeymotin

    2014-10-01

    Full Text Available In the developed world, the hazards associated with obesity have largely outstripped the risk of starvation. Obesity remains a difficult public health issue to address, due in large part to the many disciplines involved. A full understanding requires knowledge in the fields of genetics, endocrinology, psychology, sociology, economics, and public policy – among others. In this short review, which serves as an introduction to the Frontiers in Endocrinology research topic, we address one cross-disciplinary relationship: the interaction between the hunger/satiation neural circuitry, an individual’s perceived locus of control, and the risk for obesity. Mammals have evolved a complex system for modulating energy intake. Overlaid on this, in humans, there exists a wide variation in perceived locus of control – that is, the extent to which an individual believes to be in charge of the events that affect them. Whether one has primarily an internal or external locus of control itself affects, and is affected by, external and physiological factors and has been correlated with the risk for obesity. Thus, the path from hunger and satiation to an individual’s actual behavior may often be moderated by psychological factors, included among which is locus of control.

  13. Locus of control and obesity.

    Science.gov (United States)

    Neymotin, Florence; Nemzer, Louis R

    2014-01-01

    In the developed world, the hazards associated with obesity have largely outstripped the risk of starvation. Obesity remains a difficult public health issue to address, due in large part to the many disciplines involved. A full understanding requires knowledge in the fields of genetics, endocrinology, psychology, sociology, economics, and public policy - among others. In this short review, which serves as an introduction to the Frontiers in Endocrinology research topic, we address one cross-disciplinary relationship: the interaction between the hunger/satiation neural circuitry, an individual's perceived locus of control, and the risk for obesity. Mammals have evolved a complex system for modulating energy intake. Overlaid on this, in humans, there exists a wide variation in "perceived locus of control" - that is, the extent to which an individual believes to be in charge of the events that affect them. Whether one has primarily an internal or external locus of control itself affects, and is affected by, external and physiological factors and has been correlated with the risk for obesity. Thus, the path from hunger and satiation to an individual's actual behavior may often be moderated by psychological factors, included among which is locus of control.

  14. Causes of metabolic syndrome and obesity-related co-morbidities Part 1: A composite unifying theory review of human-specific co-adaptations to brain energy consumption.

    Science.gov (United States)

    McGill, Anne-Thea

    2014-01-01

    The medical, research and general community is unable to effect significantly decreased rates of central obesity and related type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer. All conditions seem to be linked by the concept of the metabolic syndrome (MetS), but the underlying causes are not known. MetS markers may have been mistaken for causes, thus many treatments are destined to be suboptimal. The current paper aims to critique current paradigms, give explanations for their persistence, and to return to first principles in an attempt to determine and clarify likely causes of MetS and obesity related comorbidities. A wide literature has been mined, study concepts analysed and the basics of human evolution and new biochemistry reviewed. A plausible, multifaceted composite unifying theory is formulated. The basis of the theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A 'dual system' is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals, becoming highly energy efficient in humans. The still-evolving, complex human cortico-limbic-striatal system generates strong behavioural drives for energy dense food procurement, including motivating agricultural technologies and social system development. Addiction to such foods, leading to neglect of nutritious but less appetizing 'common or garden' food, appears to have occurred. Insufficient consumption of food micronutrients prevents optimal human NRF2 function. Inefficient oxidation of excess energy forces central and non-adipose cells to store excess toxic lipid. Oxidative stress and

  15. Gender and obesity specific MicroRNA expression in adipose tissue from lean and obese pigs

    DEFF Research Database (Denmark)

    Mentzel, Caroline M. Junker; Anthon, Christian; Jacobsen, Mette Juul

    2015-01-01

    Obesity is a complex condition that increases the risk of life threatening diseases such as cardiovascular disease and diabetes. Studying the gene regulation of obesity is important for understanding the molecular mechanisms behind the obesity derived diseases and may lead to better intervention...... and treatment plans. MicroRNAs (miRNAs) are short non-coding RNAs regulating target mRNA by binding to their 3'UTR. They are involved in numerous biological processes and diseases, including obesity. In this study we use a mixed breed pig model designed for obesity studies to investigate differentially...... expressed miRNAs in subcutaneous adipose tissue by RNA sequencing (RNAseq). Both male and female pigs are included to explore gender differences. The RNAseq study shows that the most highly expressed miRNAs are in accordance with comparable studies in pigs and humans. A total of six mi...

  16. Breastfeeding: a natural defence against obesity?

    Directory of Open Access Journals (Sweden)

    Gabriella D'Angelo

    2015-11-01

    Full Text Available Today, obesity represents one of the most serious health problems facing both children and adults. Childhood obesity has several causes, including genetic factors, dietary habits, personal behaviours, and interaction of all of these. It often leads to adult obesity, which causes health problems including heart disease, diabetes, and even early death. Thus, many studies have investigated possible measures to prevent childhood obesity, and breastfeeding is considered an important early preventive intervention. Despite the fact that several milk formulas have been demonstrated to be safe and effective for feeding both term and premature infants, for its immunological and nutritional qualitative advantages, human milk is nowadays universally recognized as the optimal feeding choice for healthy, sick and preterm infants. To date, it is however still unclear whether breastfeeding can prevent childhood obesity. In fact, literature data provide controversial results, probably due to several confounding factors, including maternal habits, age, level of education, lifestyle, race, parity, pregnancy complications, types of delivery, and infant health factors. Thus, whether breastfeeding protects against obesity is still unclear. Further researches, by reducing the influence of confounding factors and improving the accuracy of the effect estimate, are needed to confirm the validity of the role of breastfeeding in reducing the risk of developing childhood overweight. This review briefly summarizes what is known on the possible relationship between breastfeeding and prevention of obesity development.

  17. Applications of Systems Genetics and Biology for Obesity Using Pig Models

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Kadarmideen, Haja N.

    2016-01-01

    approach, a branch of systems biology. In this chapter, we will describe the state of the art of genetic studies on human obesity, using pig populations. We will describe the features of using the pig as a model for human obesity and briefly discuss the genetics of obesity, and we will focus on systems......In many biomedical research areas, animals have been used as a model to increase the understanding of molecular mechanisms involved in human diseases. One of those areas is human obesity, where porcine models are increasingly used. The pig shows genetic and physiological features that are very...... similar to humans and have shown to be an excellent model for human obesity. Using pig populations, many genetic studies have been performed to unravel the genetic architecture of human obesity. Most of them are pinpointing toward single genes, but more and more studies focus on a systems genetics...

  18. Neighborhoods and obesity.

    Science.gov (United States)

    Black, Jennifer L; Macinko, James

    2008-01-01

    This review critically summarizes the literature on neighborhood determinants of obesity and proposes a conceptual framework to guide future inquiry. Thirty-seven studies met all inclusion criteria and revealed that the influence of neighborhood-level factors appears mixed. Neighborhood-level measures of economic resources were associated with obesity in 15 studies, while the associations between neighborhood income inequality and racial composition with obesity were mixed. Availability of healthy versus unhealthy food was inconsistently related to obesity, while neighborhood features that discourage physical activity were consistently associated with increased body mass index. Theoretical explanations for neighborhood-obesity effects and recommendations for strengthening the literature are presented.

  19. NEURAXIAL ANESTHESIA and OBESITY

    Directory of Open Access Journals (Sweden)

    Aynur sahin

    2013-09-01

    Full Text Available Obesity is one of the serious condition that commonly effects health in modern age. It was reported that obesity was three-fold increased in the last three decades. According to the statement by World Health Organisation in 2005, 700 million people will be estimated obese in 2015. While neuraxial anesthesia is a commonly used technique in the worldwide, the process may have difficulties in obese patients. In this review, the pathophysiological changes and challenges in neuraxial anesthesia procedure in obesity were assessed with current literatures. [J Contemp Med 2013; 3(3.000: 234-236

  20. One Health Solutions to Obesity in People and Their Pets

    OpenAIRE

    Bartges, J.; Kushner, R.F.; Michel, K.E.; Sallis, R.; Day, M.J.

    2017-01-01

    Despite the high prevalence of overweight and obesity in the human and companion animal populations, and the global trends for increasing numbers of affected people and pets, there are few successful interventions that are proven to combat this complex multifactorial problem. One key strategy involves effective communication between human and veterinary healthcare professionals with patients and clients about obesity. In human healthcare, the focus of communication should be on physical activ...

  1. Obesity and nosocomial infections.

    Science.gov (United States)

    Huttunen, R; Karppelin, M; Syrjänen, J

    2013-09-01

    The prevention of healthcare-associated infections (HCAIs) is a major goal in modern healthcare. Intrinsic, patient-related factors may contribute to the risk of HCAIs. To review the association between obesity and the risk and outcome of HCAIs. A PubMed search of relevant studies on obesity and nosocomial infections and obesity and dosing of antimicrobials. Search terms were: 'obesity', 'infection', 'nosocomial infection', 'surgical site infection', 'critical care unit', 'bacteremia', 'urinary tract infection', 'health care associated infection'. Obesity has been shown to be associated with an increased risk of HCAIs in several studies. The association is most clear in cardiac, vascular, orthopaedic and gastrointestinal surgery. Body mass index (BMI) data are frequently recorded in patients undergoing surgical and invasive procedures. The recording of BMI data is not systematic in the literature and in many studies median BMI of the control group or reference group (normal weight) also indicates overweight or obesity. Thus, clear BMI cut-offs for increased infection risk cannot be determined. Obesity is frequently associated with underdosing of antimicrobials in both prophylaxis and treatment of HCAIs. Studies indicate that obesity affects the pharmacokinetics of antimicrobial drugs. However, there are no dosing recommendations for antimicrobial use in obesity. Obesity increases the risk of nosocomial infections and is frequently associated with underdosing of antimicrobials in both prophylaxis and treatment of HCAIs. A challenge in future hospital hygiene prevention lies in our capacity to combat obesity epidemics. © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  2. Hormonal contraception and obesity.

    Science.gov (United States)

    Simmons, Katharine B; Edelman, Alison B

    2016-11-01

    The rising rate of overweight and obesity is a public health crisis in the United States and increasingly around the globe. Rates of contraceptive use are similar among women of all weights, but because contraceptive development studies historically excluded women over 130% of ideal body weight, patients and providers have a gap in understanding of contraceptive efficacy for obese and overweight women. Because of a range of drug metabolism alterations in obesity, there is biologic plausibility for changes in hormonal contraception effectiveness in obese women. However, these pharmacokinetic changes are not linearly related to body mass index or weight, and it is unknown what degree of obesity begins to affect pharmacokinetic or pharmacodynamics processes. Overall, most studies of higher quality do not demonstrate a difference in oral contraceptive pill effectiveness in obese compared with non-obese women. However, data are scant for women in the highest categories of obesity, and differences by progestin type are incompletely understood. Effectiveness of most non-oral contraceptives does not seem to be compromised in obesity. Exceptions to this include the combined hormonal patch and oral levonorgestrel emergency contraception, which may have lower rates of effectiveness in obese women. The purpose of this review is to summarize evidence on contraceptive use in women with obesity, including differences in steroid hormone metabolism, contraceptive effectiveness, and safety, compared with women of normal weight or body mass index using the same methods. Copyright © 2016 American Society for Reproductive Medicine. All rights reserved.

  3. Obesity and kidney disease

    Directory of Open Access Journals (Sweden)

    Geraldo Bezerra da Silva Junior

    Full Text Available Abstract Obesity has been pointed out as an important cause of kidney diseases. Due to its close association with diabetes and hypertension, excess weight and obesity are important risk factors for chronic kidney disease (CKD. Obesity influences CKD development, among other factors, because it predisposes to diabetic nephropathy, hypertensive nephrosclerosis and focal and segmental glomerulosclerosis. Excess weight and obesity are associated with hemodynamic, structural and histological renal changes, in addition to metabolic and biochemical alterations that lead to kidney disease. Adipose tissue is dynamic and it is involved in the production of "adipokines", such as leptin, adiponectin, tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-β and angiotensin-II. A series of events is triggered by obesity, including insulin resistance, glucose intolerance, dyslipidemia, atherosclerosis and hypertension. There is evidence that obesity itself can lead to kidney disease development. Further studies are required to better understand the association between obesity and kidney disease.

  4. Comparison of thermogenic sympathetic response to food intake between obese and non-obese young women.

    Science.gov (United States)

    Matsumoto, T; Miyawaki, C; Ue, H; Kanda, T; Yoshitake, Y; Moritani, T

    2001-02-01

    Sympathetic nervous system abnormality in humans is still a matter of debate. The present study was designed to examine diet-induced autonomic nervous system activity and metabolic change in obese and non-obese young women. Sixteen age- and height-matched obese and non-obese young women participated in this study. Sympathovagal activities were assessed by means of our newly developed spectral analysis procedure of heart-rate variability during the resting condition and after mixed-food ingestion (480 kcal). Energy expenditure was also measured under these two conditions. There was no significant difference in any of the parameters of the heart-rate variability between the obese group and control group during the resting condition. In the control group, both absolute values (221.5 +/- 54.5 vs. 363.8 +/- 43.7 ms2, p frequency component and global sympathetic nervous system index (1.46 +/- 0.19 vs. 3.26 +/- 0.61, p food ingestion compared with the values obtained after resting condition. However, no such sympathetic response was found in the obese group. Energy expenditure increased in the two groups after the meal, but the magnitude of the increase above the preprandial resting condition was significantly greater in the control group than in the obese group (11.2 +/- 2.3 vs. 6.7 +/- 0.8%, p food intake, which might be related to lowered capacity of thermogenesis and the state of obesity.

  5. Human microbiomics

    OpenAIRE

    Rajendhran, J.; Gunasekaran, P.

    2010-01-01

    The sequencing of the human genome has driven the study of human biology in a significant way and enabled the genome-wide study to elucidate the molecular basis of complex human diseases. Recently, the role of microbiota on human physiology and health has received much attention. The influence of gut microbiome (the collective genomes of the gut microbiota) in obesity has been demonstrated, which may pave the way for new prophylactic and therapeutic strategies such as bacteriotherapy. The sig...

  6. The Financial Costs, Behaviour and Psychology of Obesity: A One Health Analysis.

    Science.gov (United States)

    Bomberg, E; Birch, L; Endenburg, N; German, A J; Neilson, J; Seligman, H; Takashima, G; Day, M J

    2017-05-01

    People who are overweight or have obesity are estimated to comprise 30% of the global population and up to 59% of companion dogs and cats are estimated to be above their optimal body weight. The prevalence of human and companion obesity is increasing. The direct and indirect costs of obesity and associated comorbidities are significant for human and veterinary healthcare. There are numerous similarities between obesity in people and companion animals, likely related to the shared environmental and lifestyle elements of this multifactorial disease. While the study of human obesity is relatively robust, research conducted in pets is generally limited to small studies, studies with cross-sectional designs or reports that have yet to be replicated. Greater understanding of human obesity may elucidate some of the factors driving the more recent rise in pet obesity. In particular, there are overlapping features of obesity in children and pets that are, in part, related to dependency on their 'parents' for care and feeding. When feeding is used in a coercive and controlling fashion, it may lead to undesirable feeding behaviour and increase the risk for obesity. A 'responsive parenting' intervention teaches parents to respond appropriately to hunger-satiety cues and to recognize and respond to others' distress. Such interventions may impact on childhood overweight and obesity and have the potential to be adapted for use with companion animals. Social behaviour towards people with obesity or owners of pets with obesity is often driven by beliefs about the cause of the obesity. Educating healthcare professionals and the public about the multifactorial nature of this complex disease process is a fundamental step in reducing the bias and stigma associated with obesity. Children living in low-income households have particularly high rates of obesity and as household income falls, rates of obesity also rise in pets and their owners. There are risk regulators (i.e. dynamic

  7. Could viruses contribute to the worldwide epidemic of obesity?

    Science.gov (United States)

    Atkinson, Richard L

    2008-01-01

    The prevalence of obesity in children increased rapidly starting about 1980 in both developed and developing countries. Studies of changes in diet and physical activity, television watching, and food advertisements on television suggest that these are not sufficient to explain the epidemic. The pattern of rapid spread is suggestive of an infectious origin. The concept of virus-induced obesity is not new. Eight viruses have been shown to cause obesity in animals and there is evidence for virus-induced obesity in humans. Recent evidence on animal and human adenoviruses suggests that these adenoviruses may infect adipocytes to alter enzymes and transcription factors resulting in accumulation of triglycerides and differentiation of preadipocytes into mature adipocytes. The E4orf1 gene of Ad-36 has been shown to be responsible for the adipogenic effect. It appears that a portion of the worldwide epidemic of obesity since 1980 could be due to infections with human adenoviruses.

  8. Upper gastrointestinal sensitivity to meal-related signals in adult humans - relevance to appetite regulation and gut symptoms in health, obesity and functional dyspepsia.

    Science.gov (United States)

    Feinle-Bisset, Christine

    2016-08-01

    Both the stomach and small intestine play important roles in sensing the arrival of a meal, and its physico-chemical characteristics, in the gastrointestinal lumen. The presence of a meal in the stomach provides a distension stimulus, and, as the meal empties into the small intestine, nutrients interact with small intestinal receptors, initiating the release of gut hormones, associated with feedback regulation of gastrointestinal functions, including gut motility, and signaling to the central nervous system, modulating eating behaviours, including energy intake. Lipid appears to have particularly potent effects, also in close interaction with, and modulating the effects of, gastric distension, and involving the action of gut hormones, particularly cholecystokinin (CCK). These findings have not only provided important, and novel, insights into how gastrointestinal signals interact to modulate subjective appetite perceptions, including fullness, but also laid the foundation for an increasing appreciation of the role of altered gastrointestinal sensitivities, e.g. as a consequence of excess dietary intake in obesity, or underlying the induction of gastrointestinal symptoms in functional dyspepsia (a condition characterized by symptoms, including bloating, nausea and early fullness, amongst others, after meals, particularly those high in fat, in the absence of any structural or functional abnormalities in the gastrointestinal tract). This paper will review the effects of dietary nutrients, particularly lipid, on gastrointestinal function, and associated effects on appetite perceptions and energy intake, effects of interactions of gastrointestinal stimuli, as well as the role of altered gastrointestinal sensitivities (exaggerated, or reduced) in eating-related disorders, particularly obesity and functional dyspepsia. Copyright © 2016. Published by Elsevier Inc.

  9. The Impact of Obesity on Developmental Coordination Disorder in Adolescence

    Science.gov (United States)

    Wagner, Matthias Oliver; Kastner, Julia; Petermann, Franz; Jekauc, Darko; Worth, Annette; Bos, Klaus

    2011-01-01

    Developmental coordination disorder (DCD) as well as overweight and obesity are of increasing importance in the study of human development. Data on the relation between DCD and obesity in adolescence are of particular interest because both phenomena are unlikely to disappear with age. The objective of this study was to determine the impact of…

  10. Obesity Risk Prediction among Women of Upper Egypt: The impact ...

    African Journals Online (AJOL)

    Obesity is one of the main threats to the human health. It is a major risk factor for hyperinsulinemia, hypertension, hyperlipidemia, type II diabetes mellitus, and atherosclerotic cardiovascular disease. FTO gene variants have been associated with obesity and diabetes mellitus in different populations, but its role in the ...

  11. Effects of Repeated Acute Stress in Obese and Non-Obese Rats

    Science.gov (United States)

    2008-04-02

    periphery, affecting the immune, cardiovascular , and metabolic systems . Effects of Stress In human and rodents, stress can result in negative emotions...Grunberg, N.E., Popp, K.A., & Winders, S.E. (1988). Effects of nicotine on body weight in rats with access to " junk " foods . Psychopharmacology, 94(4...examined effects of repeated acute stress on genetically obese and non-obese male and female rats. In Experiment I, stress: (1) decreased bland food

  12. Diet-induced obesity in zebrafish shares common pathophysiological pathways with mammalian obesity

    Directory of Open Access Journals (Sweden)

    Shimada Yasuhito

    2010-10-01

    Full Text Available Abstract Background Obesity is a multifactorial disorder influenced by genetic and environmental factors. Animal models of obesity are required to help us understand the signaling pathways underlying this condition. Zebrafish possess many structural and functional similarities with humans and have been used to model various human diseases, including a genetic model of obesity. The purpose of this study was to establish a zebrafish model of diet-induced obesity (DIO. Results Zebrafish were assigned into two dietary groups. One group of zebrafish was overfed with Artemia (60 mg dry weight/day/fish, a living prey consisting of a relatively high amount of fat. The other group of zebrafish was fed with Artemia sufficient to meet their energy requirements (5 mg dry weight/day/fish. Zebrafish were fed under these dietary protocols for 8 weeks. The zebrafish overfed with Artemia exhibited increased body mass index, which was calculated by dividing the body weight by the square of the body length, hypertriglyceridemia and hepatosteatosis, unlike the control zebrafish. Calorie restriction for 2 weeks was applied to zebrafish after the 8-week overfeeding period. The increased body weight and plasma triglyceride level were improved by calorie restriction. We also performed comparative transcriptome analysis of visceral adipose tissue from DIO zebrafish, DIO rats, DIO mice and obese humans. This analysis revealed that obese zebrafish and mammals share common pathophysiological pathways related to the coagulation cascade and lipid metabolism. Furthermore, several regulators were identified in zebrafish and mammals, including APOH, IL-6 and IL-1β in the coagulation cascade, and SREBF1, PPARα/γ, NR1H3 and LEP in lipid metabolism. Conclusion We established a zebrafish model of DIO that shared common pathophysiological pathways with mammalian obesity. The DIO zebrafish can be used to identify putative pharmacological targets and to test novel drugs for the

  13. Psychosocial aspects of obesity.

    Science.gov (United States)

    Vaidya, Varsha

    2006-01-01

    Obese patients have many physical limitations and much psychiatric burden to overcome. Several studies have shown that the prevalence of psychiatric morbidity in the obese is similar to those with normal weight. However, in obese patients seeking treatment there is an increased prevalence (40-60%) of psychiatric morbidity, most commonly depression. It is difficult to separate the effects of depression on obesity and, on the contrary, the neuroendocrine changes associated with stress and depression may cause metabolic changes that predispose and perpetuate obesity. The stigma associated with obesity causes bullying in school as well as childhood psychiatric morbidity. Prejudice is not limited to the general public but exists among health professionals too. This chapter discusses the treatment of depression in obesity and the psychiatric evaluation of the pre-bariatric surgery patient. Education of society, starting with schools and including healthcare professionals will reduce bias and stigma as well as assist this vulnerable group of patients to seek help for their obesity and the many problems that come with it. Given that by the year 2025 obesity will be the world's number one health problem with the US leading the way, it is very important that we pursue preventive measures as well as encourage research for treatments of obesity.

  14. Is obesity a disease?

    Directory of Open Access Journals (Sweden)

    Šumarac-Dumanović Mirjana 0000-0002-6216-6650

    2017-01-01

    Full Text Available Obesity is a complex entity that can have many causes, such as endocrine (like thyroid dysfunction or hyperfunctioning of the suprarenall gland-Cushing’s syndrome but often obesity is from a combination of inactivity and overeating. On the other side, there are genetic factors that produce a tendency to overweight even with the consumption of what would be for most people an appropriate number of calories. Whether the causes are hormonal, genetic or reside in the brain (its reward system or the circuitry that underlies habit, perception of portion size, the choice of food... is often difficult to sort out. Proponents contend that obesity is a disease because it meets the definition of disease. Obesity decreases life expectancy and impairs the normal body functions, also it can be caused by genetic factors. Opponents contend that obesity is not a disease because it is a preventable risk factor for other diseases. Obesity is the result of eating too much as well as it is caused by exercising too little. Formaly disease or condition obesity is associated with a variety of diseases such as type 2 diabetes, atherosclerosis, cardiovascular diseases and certain cancers, and may also be responsible for high rates of morbidity and mortality. Understanding the pathophysiology of obesity has grown significantly over the last few decades. Pathogenetic mechanisms in obesity and in the development of comorbidities that accompany obesity exhibit many of the characteristics of inflammatory processes. A key role in the pathogenesis of obesity could play the immune system. Despite identifying many critical players in these processes and finding new therapeutic modalities in the fight against obesity, treatment of obesity is still a great challenge and mostly with not-so-successful outcomes.

  15. [Obesity and diabetes mellitus].

    Science.gov (United States)

    Tron'ko, N D; Zak, K P

    2013-12-01

    New literature data and the results of own researches concerning the role of excessive body weight and the development of type 2 diabetes mellitus in humans are presented in the analytical review. Inaccordance with current insights, obesity and type 2 diabetes are considered diseases of inflammatory nature, characterized by systemic chronic low-grade inflammation, where different kinds of cytokines are cardinally involved. Unfavourable life style, i.e. excessive, high-energy, and irrational nutrition--an excessive consumption of animal fats and foods containing the high amount of glucose and starch with an insufficient use of high fiber vegetables, fish and vitamin D, and also sedentary, inactive life style leads to adipocyte hypertrophy and migration of M1 macrophages into the adipose tissue (AT). As a result, there is a low-grade inflammation accompanied by an increased production of proinflammatory cytokines (IL-1, IL-6, TNF-α, etc.), adipokines (leptin, resistin, visfatin etc.) and chemokines (CCL2, CCL5, CCL26 and CX3C). Under the influence of these cytokines, on the one hand, IR "is emerged", and on the other--there is apoptosis of the β-cells, that should be followed by the occurrence of clinically diagnosed type 2 diabetes. However, there is also the opposite system in humans, protecting the organism from the development of type 2 diabetes, and including an increase in the formation of M2 macrophages and the increased formation of secretion of antidiabetic cytokines (IL-4, IL-10, IL-13, etc.) and adiponectin.

  16. Deep brain stimulation for obesity: past, present, and future targets.

    Science.gov (United States)

    Dupré, Derrick A; Tomycz, Nestor; Oh, Michael Y; Whiting, Donald

    2015-06-01

    The authors review the history of deep brain stimulation (DBS) in patients for treating obesity, describe current DBS targets in the brain, and discuss potential DBS targets and nontraditional stimulation parameters that may improve the effectiveness of DBS for ameliorating obesity. Deep brain stimulation for treating obesity has been performed both in animals and in humans with intriguing preliminary results. The brain is an attractive target for addressing obesity because modulating brain activity may permit influencing both sides of the energy equation--caloric intake and energy expenditure.

  17. The Financial Costs, Behaviour and Psychology of Obesity : A One Health Analysis

    NARCIS (Netherlands)

    Bomberg, E.; Birch, L.; Endenburg, N.; German, A.J.; Neilson, J.; Seligman, H.; Takashima, G.; Day, M.J.

    People who are overweight or have obesity are estimated to comprise 30% of the global population and up to 59% of companion dogs and cats are estimated to be above their optimal body weight. The prevalence of hu-man and companion obesity is increasing. The direct and indirect costs of obesity and

  18. [The pharmacotherapy of obesity].

    Science.gov (United States)

    Budai, Kinga Anna; Mirzahosseini, Arash; Noszál Béla; Tóth, Gergő

    2015-01-01

    Obesity is considered the most concerning and blatantly visible--yet most neglected--public health problem by the WHO. The steadily increasing number of overweight and obese people has reached 2.3 billion and 700 million worldwide, respectively. Obesity is a complex condition, one that presents serious health risks with respect to type 2 diabetes, ischemic heart disease, and hypertension, therefore controlling the global obesity epidemic decreases not only health problems, but also expenditure. The underlying cause of obesity is a metabolic disorder of genetic, central nervous system or endocrine etiology that manifests in increased nutritional intake and/or decreased physical activity ultimately leading to excessive lipogenesis. The natural treatment of obesity, that is often advised, is comprised of healthy lifestyle choices, namely low-calorie diet and exercise. However, the pharmaceutic treatment of obesity is just as important; having a better compliance rate, anti-obesity drugs also improve quality of life and patient-care outcome concerning accompanying diseases. In most countries only one drug is currently available against obesity: orlistat, which is a specific and irreversible lipase inhibitor. One of the reasons for the scarce number of anti-obesity drugs is the complex pathomechanism involved in obesity. Interference with the intricate biochemical processes that govern alimentation may lead to widespread adverse effects. The advances of the field however, have prompted novel drug leads. In the past few years FDA has approved new drugs for the treatment of obesity, recently liraglutide in 2014. The approval of drug combinations, such as phentermine/topiramate and bupropion/naltrexone are also noteworthy, the components of which have been previously approved, but not necessarily for obesity as main indication. Furthermore, there are many anti-obesity drug candidates currently in clinical phase trials, with promisingly modest adverse effect profiles; hence

  19. Obesity and pregnancy

    DEFF Research Database (Denmark)

    Andreasen, Kirsten Riis; Andersen, Malene Lundgren; Schantz, Anne Louise

    2004-01-01

    BACKGROUND: As obesity is an increasing problem among fertile women, it is crucial that specialists involved in the treatment of these women be aware of the risks of complications and know how to deal with them. Complications associated with obesity in pregnancy are gestational diabetes mellitus......, hypertensive disorders, and thromboembolic complications. Complications associated with obesity in labor are augmentation, early amniotomy, cephalopelvic disproportion, cesarean section, and perioperative morbidity. Complications associated with obesity in children are macrosomia, shoulder dystocia, small...... for gestational age, late fetal death, and congenital malformations, especially neural tube defects. OBJECTIVE: The aim was to review the potential complications associated with obesity and pregnancy. RESULTS: Obesity is associated with a higher risk of all reviewed complications except small for gestational age....

  20. Genetics of Childhood Obesity

    Directory of Open Access Journals (Sweden)

    Jianhua Zhao

    2011-01-01

    Full Text Available Obesity is a major health problem and an immense economic burden on the health care systems both in the United States and the rest of the world. The prevalence of obesity in children and adults in the United States has increased dramatically over the past decade. Besides environmental factors, genetic factors are known to play an important role in the pathogenesis of obesity. Genome-wide association studies (GWAS have revealed strongly associated genomic variants associated with most common disorders; indeed there is general consensus on these findings from generally positive replication outcomes by independent groups. To date, there have been only a few GWAS-related reports for childhood obesity specifically, with studies primarily uncovering loci in the adult setting instead. It is clear that a number of loci previously reported from GWAS analyses of adult BMI and/or obesity also play a role in childhood obesity.

  1. Obesity and pregnancy

    DEFF Research Database (Denmark)

    Andreasen, Kirsten Riis; Andersen, Malene Lundgren; Schantz, Anne Louise

    2004-01-01

    , hypertensive disorders, and thromboembolic complications. Complications associated with obesity in labor are augmentation, early amniotomy, cephalopelvic disproportion, cesarean section, and perioperative morbidity. Complications associated with obesity in children are macrosomia, shoulder dystocia, small......BACKGROUND: As obesity is an increasing problem among fertile women, it is crucial that specialists involved in the treatment of these women be aware of the risks of complications and know how to deal with them. Complications associated with obesity in pregnancy are gestational diabetes mellitus...... for gestational age, late fetal death, and congenital malformations, especially neural tube defects. OBJECTIVE: The aim was to review the potential complications associated with obesity and pregnancy. RESULTS: Obesity is associated with a higher risk of all reviewed complications except small for gestational age....

  2. Obesity in critical care.

    Science.gov (United States)

    Joffe, Aaron; Wood, Ken

    2007-04-01

    To review literature germane to the care of critically ill obese patients with emphasis upon the pathophysiology of obesity and its impact on clinical management. Obesity continues to be a health epidemic of the industrialized world, and is associated with substantial morbidity and mortality. Chronic obesity results in derangements in cardiovascular, respiratory and metabolic function. Drug administration may be effected depending on the lipophilicity of the molecule administered. The ability to gain vascular access is often impaired because of large body habitus and should be aided with ultrasound guidance. The fidelity of blood pressure monitoring can also be adversely affected, necessitating the use of direct intraarterial monitoring. Obesity has pathophysiologic effects upon all major organ systems. A thorough knowledge of these effects and specific intensive care unit-related issues are necessary for clinicians to anticipate common complications and provide timely and effective treatment for the obese intensive care unit patient.

  3. Pediatric obesity. An introduction.

    Science.gov (United States)

    Yanovski, Jack A

    2015-10-01

    The prevalence of child and adolescent obesity in the United States increased dramatically between 1970 and 2000, and there are few indications that the rates of childhood obesity are decreasing. Obesity is associated with myriad medical, psychological, and neurocognitive abnormalities that impact children's health and quality of life. Genotypic variation is important in determining the susceptibility of individual children to undue gains in adiposity; however, the rapid increase in pediatric obesity prevalence suggests that changes to children's environments and/or to their learned behaviors may dramatically affect body weight regulation. This paper presents an overview of the epidemiology, consequences, and etiopathogenesis of pediatric obesity, serving as a general introduction to the subsequent papers in this Special Issue that address aspects of childhood obesity and cognition in detail. Published by Elsevier Ltd.

  4. Obesity and asthma

    DEFF Research Database (Denmark)

    Sivapalan, Pradeesh; Diamant, Zuzana; Ulrik, Charlotte Suppli

    2015-01-01

    PURPOSE OF REVIEW: Obesity has significant impact on asthma incidence and manifestations. The purpose of the review is to discuss recent observations regarding the association between obesity and asthma focusing on underlying mechanisms, clinical presentation, response to therapy and effect...... of weight reduction. RECENT FINDINGS: Clinical and epidemiological studies indicate that obese patients with asthma may represent a unique phenotype, which is more difficult to control, less responsive to asthma medications and by that may have higher healthcare utilization. A number of common comorbidities...... have been linked to both obesity and asthma, and may, therefore, contribute to the obese-asthma phenotype. Furthermore, recently published studies indicate that even a modest weight reduction can improve clinical manifestations and outcome of asthma. SUMMARY: Compared with normal-weight patients, obese...

  5. Longitudinal associations between poverty and obesity from birth through adolescence.

    Science.gov (United States)

    Lee, Hedwig; Andrew, Megan; Gebremariam, Achamyeleh; Lumeng, Julie C; Lee, Joyce M

    2014-05-01

    We examined the relationship between timing of poverty and risk of first-incidence obesity from ages 3 to 15.5 years. We used the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (1991-2007) to study 1150 children with repeated measures of income, weight, and height from birth to 15.5 years in 10 US cities. Our dependent variable was the first incidence of obesity (body mass index ≥ 95th percentile). We measured poverty (income-to-needs ratio obesity. Poverty prior to age 2 years was associated with risk of obesity by age 15.5 years in fully adjusted models. These associations did not vary by gender. Our findings suggest that there are enduring associations between early life poverty and adolescent obesity. This stage in the life course may serve as a critical period for both poverty and obesity prevention.

  6. Obesity-Related Diseases Dietary Modulation of the Gut Microbiota

    DEFF Research Database (Denmark)

    Brahe, Lena Kirchner

    The prevalence of obesity has increased epidemically during the past four decades and worldwide more than half a billion adults are now obese. Obesity increases the risk of type 2 diabetes, cardiovascular diseases and cancer, which are among the leading causes of death worldwide. Thus, effective ...... for prevention. The main purpose of this PhD was to explore the effect of dietary modulation of the gut microbiota on disease markers in obese individuals....... strategies to reduce obesity-related morbidity and mortality are essential. It has been hypothesized that the microbes in the human gut are involved in the development of obesity-related diseases and that intake of nutrients affecting the gut microbial community in specific ways, can be a new strategy...

  7. Obesity-Related Diseases Dietary Modulation of the Gut Microbiota

    DEFF Research Database (Denmark)

    Brahe, Lena Kirchner

    The prevalence of obesity has increased epidemically during the past four decades and worldwide more than half a billion adults are now obese. Obesity increases the risk of type 2 diabetes, cardiovascular diseases and cancer, which are among the leading causes of death worldwide. Thus, effective...... strategies to reduce obesity-related morbidity and mortality are essential. It has been hypothesized that the microbes in the human gut are involved in the development of obesity-related diseases and that intake of nutrients affecting the gut microbial community in specific ways, can be a new strategy...... for prevention. The main purpose of this PhD was to explore the effect of dietary modulation of the gut microbiota on disease markers in obese individuals....

  8. In Search of New Therapeutic Targets in Obesity Treatment: Sirtuins

    Directory of Open Access Journals (Sweden)

    Alina Kurylowicz

    2016-04-01

    Full Text Available Most of the available non-invasive medical therapies for obesity are non-efficient in a long-term evaluation; therefore there is a constant need for new methods of treatment. Research on calorie restriction has led to the discovery of sirtuins (silent information regulators, SIRTs, enzymes regulating different cellular pathways that may constitute potential targets in the treatment of obesity. This review paper presents the role of SIRTs in the regulation of glucose and lipid metabolism as well as in the differentiation of adipocytes. How disturbances of SIRTs’ expression and activity may lead to the development of obesity and related complications is discussed. A special emphasis is placed on polymorphisms in genes encoding SIRTs and their possible association with susceptibility to obesity and metabolic complications, as well as on data regarding altered expression of SIRTs in human obesity. Finally, the therapeutic potential of SIRTs-targeted strategies in the treatment of obesity and related disorders is discussed.

  9. Effects of Maternal Obesity on Fetal Programming: Molecular Approaches

    Science.gov (United States)

    Neri, Caterina; Edlow, Andrea G.

    2016-01-01

    Maternal obesity has become a worldwide epidemic. Obesity and a high-fat diet have been shown to have deleterious effects on fetal programming, predisposing offspring to adverse cardiometabolic and neurodevelopmental outcomes. Although large epidemiological studies have shown an association between maternal obesity and adverse outcomes for offspring, the underlying mechanisms remain unclear. Molecular approaches have played a key role in elucidating the mechanistic underpinnings of fetal malprogramming in the setting of maternal obesity. These approaches include, among others, characterization of epigenetic modifications, microRNA expression, the gut microbiome, the transcriptome, and evaluation of specific mRNA expression via quantitative reverse transcription polmerase chain reaction (RT-qPCR) in fetuses and offspring of obese females. This work will review the data from animal models and human fluids/cells regarding the effects of maternal obesity on fetal and offspring neurodevelopment and cardiometabolic outcomes, with a particular focus on molecular approaches. PMID:26337113

  10. Obesity-associated biomarkers and executive function in children.

    Science.gov (United States)

    Miller, Alison L; Lee, Hannah J; Lumeng, Julie C

    2015-01-01

    There is a growing focus on links between obesity and cognitive decline in adulthood, including Alzheimer's disease. It is also increasingly recognized that obesity in youth is associated with poorer cognitive function, specifically executive functioning skills such as inhibitory control and working memory, which are critical for academic achievement. Emerging literature provides evidence for possible biological mechanisms driven by obesity; obesity-associated biomarkers such as adipokines, obesity-associated inflammatory cytokines, and obesity-associated gut hormones have been associated with learning, memory, and general cognitive function. To date, examination of obesity-associated biology with brain function has primarily occurred in animal models. The few studies examining such biologically mediated pathways in adult humans have corroborated the animal data, but this body of work has gone relatively unrecognized by the pediatric literature. Despite the fact that differences in these biomarkers have been found in association with obesity in children, the possibility that obesity-related biology could affect brain development in children has not been actively considered. We review obesity-associated biomarkers that have shown associations with neurocognitive skills, specifically executive functioning skills, which have far-reaching implications for child development. Understanding such gut-brain associations early in the lifespan may yield unique intervention implications.

  11. [Obesity and free inquiry].

    Science.gov (United States)

    Kutnowski, M

    2006-09-01

    The W.H.O. identifies obesity as one of the ten leading health risk factors. Obesity is a worldwide non-infectious pandemic with dramatic consequences, and its usual treatment comes generally to a failure. One may wonder if our therapeutic proposal is adequate, instead of speaking about the lack of willpower of our patients. The explanation of weight gain should not be reduced to a caloric balance. Obese people may have other physiological characteristics than lean ones. Examples are quoted.

  12. Obesity and contraception: controversy?

    OpenAIRE

    Goldberg RD; Cardamone SC; Murthy AS

    2012-01-01

    Rebecca D Goldberg, Stefanie C Cardamone, Amitasrigowri S MurthyDepartment of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USAAbstract: Obesity is increasing worldwide and is affecting the reproductive health of women. Contraceptive considerations are difficult in obese women given concerns about efficacy and comorbid conditions. Once surgical treatment of obesity has occurred and weight loss initiated, fertility risks increase and unintended pregnancy can ...

  13. Social influence and obesity.

    Science.gov (United States)

    Hammond, Ross A

    2010-10-01

    To review a selection of research published in the last 12 months on the role of social influence in the obesity epidemic. Recent papers add evidence to previous work linking social network structures and obesity. Social norms, both eating norms and body image norms, are identified as one major source of social influence through networks. Social capital and social stress are additional types of social influence. There is increasing evidence that social influence and social network structures are significant factors in obesity. Deeper understanding of the mechanisms of action and dynamics of social influence, and its link with other factors involved in the obesity epidemic, is an important goal for further research.

  14. [Nutrigenomics and obesity].

    Science.gov (United States)

    Palou, A; Bonet, M L; Picó, C; Rodríguez, A M

    2004-01-01

    Obesity is a multifactorial disorder affected by multiple genetic and environmental factors, in particular nutrients, and their interrelationships. Increasing knowledge of the genes and molecules involved in the development of obesity is paving the way for new methods of obesity control. In this sense, Nutrigenomics--which represents a new approach in nutrition research that joints the application of powerful functional genomics technologies, bioinformatics and molecular biology with more traditional methodologies--may orientate the design and development of new functional foods for obesity, based on the scientific knowledge of the impact of specific nutrients on the mammalian body weight control system and their mechanisms of action.

  15. Controversies in Obesity Treatment

    Directory of Open Access Journals (Sweden)

    Majid Karandish

    2015-06-01

    Full Text Available The markedly high prevalence of obesity contributes to the increased incidence of chronic diseases, such as diabetes, hypertension, sleep apnea, and heart disease. Because of high prevalence of obesity in almost all countries, it has been the focus of many researches throughout the world during the recent decades. Along with increasing researches, new concepts and controversies have been emerged. The existing controversies on the topic are so deep that some researches argue on absolutely philosophical questions such as “Is obesity a disease?” or “Is it correct to treat obesity?” These questions are based on a few theories and real data that explain obesity as a biological adaptation and also the final results of weight loss programs. Many people attempt to lose weight by diet therapy, physical activity and lifestyle modifications. Importantly, weight loss strategies in the long term are ineffective and may have unintended consequences including decreasing energy expenditure, complicated appetite control, eating disorders, reducing self-esteem, increasing the plasma and tissue levels of persistent organic pollutants that promote metabolic complications, and consequently, higher risk of repeated cycles of weight loss and weight regain. In this review, major paradoxes and controversies on obesity including classic obesity paradox, pre-obesity; fat-but-fit theory, and healthy obesity are explained. In addition, the relevant strategies like “Health at Every Size” that emphasize on promotion of global health behaviors rather than weight loss programs are explained.

  16. [Obesity in Mexico].

    Science.gov (United States)

    Dávila-Torres, Javier; González-Izquierdo, José Jesús; Barrera-Cruz, Antonio

    2015-01-01

    Excess body weight (overweight and obesity) is currently recognized as one of the most important challenges of public health in the world, given its size, speed of growth and the negative effect it has on the health of the population that suffers. Overweight and obesity significantly increases the risk of chronic no communicable diseases, premature mortality and the social cost of health. An estimated 90 % of cases of type 2 diabetes mellitus attributable to overweight and obesity. Today, Mexico is second global prevalence of obesity in the adult population, which is ten times higher than that of countries like Japan and Korea. With regard to children, Mexico ranks fourth worldwide obesity prevalence, behind Greece, USA and Italy. In our country, over 70 % of the adult population, between 30 and 60 years are overweight. The prevalence of overweight is higher in men than females, while the prevalence of obesity is higher in women than men. Until 2012, 26 million Mexican adults are overweight and 22 million obese, which represents a major challenge for the health sector in terms of promoting healthy lifestyles in the population and development of public policies to reverse this scenario epidemiology. Mexico needs to plan and implement strategies and action cost effective for the prevention and control of obesity of children, adolescents and adults. Global experience shows that proper care of obesity and overweight, required to formulate and coordinate multisectoral strategies and efficient for enhancing protective factors to health, particularly to modify individual behavior, family and community.

  17. Behavioral treatment of obesity

    Directory of Open Access Journals (Sweden)

    Táki Athanássios Cordas

    2006-03-01

    Full Text Available Great population studies do not confirm the hypothesis that atypical personality of obese would exist. Obeses in the generalpopulation do not present more psychological disturbs thanthe ones that are not obeses. Obeses adolescents and adultsare discriminated in their academic and professional lifes. Thissocial, cultural, economic and affective impoverishment seemsto be directly related to the gravity of their obesity, what means,higher the ICM (Index of Corporal Mass, bigger are thepsychological problems. This abandonment contributes to thebig risk of unchain psychiatric pictures as depression, anxyetdisturbs, drugs and alcoholic excessive consumption andalimentary disturbs. Obeses of the general population do notpresent more psychological or psychiatric symptoms than theclinical population of obeses (obeses under treatment, presentmore clinical and psychiatric problems, mainly compulsoryalimentary standards. Some studies indicate that there is alinear relation between the ICM and the highest frequency ofalimentary compulsory behavior or bulimic episode. Thepsychiatric patients negative body perception added to theirother negative perceptions about their performance in searchingsocial interaction increase the trend to the isolation. Thepsychiatric picture presence in the bariatric surgery preoperatoryin a III degree overweight pacient has not to be facedas absolute surgery counter indication since such procedurecan be the difference between giving a better life quality orwaiting for a potentially lethal complication. We cannot forgetthat the obesity itself, due to the common associatedcomorbidyties, loads a great lethality potential. The surgerycounter-indication could be relative, it depending on how muchthe psychiatric disturbs interfere on the treatment andconditioned to the rigorous psychiatric control in the anteriorand post surgical period.

  18. Obesity and pregnancy

    DEFF Research Database (Denmark)

    Andreasen, Kirsten Riis; Andersen, Malene Lundgren; Schantz, Anne Louise

    2004-01-01

    BACKGROUND: As obesity is an increasing problem among fertile women, it is crucial that specialists involved in the treatment of these women be aware of the risks of complications and know how to deal with them. Complications associated with obesity in pregnancy are gestational diabetes mellitus...... for gestational age, late fetal death, and congenital malformations, especially neural tube defects. OBJECTIVE: The aim was to review the potential complications associated with obesity and pregnancy. RESULTS: Obesity is associated with a higher risk of all reviewed complications except small for gestational age....

  19. Obesity and breastfeeding: The strength of association.

    Science.gov (United States)

    Marseglia, Lucia; Manti, Sara; D'Angelo, Gabriella; Cuppari, Caterina; Salpietro, Vincenzo; Filippelli, Martina; Trovato, Antonio; Gitto, Eloisa; Salpietro, Carmelo; Arrigo, Teresa

    2015-06-01

    Obesity and attendant co-morbidities are an emergent problem in public health. Much attention has focused on prevention, especially during the perinatal period. Breastfeeding is considered a possible protective factor for obesity in childhood, influencing gene-neuroendocrine-environment-lifestyle interaction. Therefore, breastfeeding and its longer duration are probably associated with lower development of childhood obesity. Through human milk, but not formula, the child assumes greater bioactive factors contributing to immunological, endocrine, development, neural and psychological benefits. Contrarily, other studies did not confirm a critical role of breast milk. Confounding factors, especially maternal pre-pregnancy overweight, may influence breastfeeding effects. This review summarises what is known about the possible relationship between breastfeeding and prevention of obesity development. Breastfeeding appears to represent a protective factor for obesity in childhood, although evidence is still controversial and underlying mechanisms unclear. Further research is needed to improve knowledge on overweight/obesity and breastfeeding. Copyright © 2015 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  20. 'Metabolically healthy obesity': origins and implications.

    Science.gov (United States)

    Denis, Gerald V; Obin, Martin S

    2013-02-01

    When humans eat more and exercise less, they tend to become obese and unhealthy. The molecular pathways that link obesity to serious diseases like Type 2 diabetes and cardiovascular disease have become a subject of intensive scientific investigation because the exploding prevalence of obesity worldwide represents a grave new threat to the health of hundreds of millions of people. However, obesity is not always destiny. Two important clinical populations have been valuable to understand the mechanisms behind this conundrum: individuals who exhibit metabolic dysfunction, diabetes and elevated cardiovascular disease risk despite a lean body type, and individuals who are relatively protected from these dangers despite significant obesity. Study of this second group of 'metabolically healthy obese' people in particular has been revealing because such individuals exhibit specific, identifiable, anatomic, cellular and molecular features that set them apart from the rest of us who suffer declining health with increasing weight. Here, we examine some of these features, including some mouse models that are informative of mechanism, and suggest hypotheses for further study, including the possibility that genes and pathways of the immune system might offer new diagnostic or therapeutic targets. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Dietary Anthocyanins against Obesity and Inflammation

    Directory of Open Access Journals (Sweden)

    Yoon-Mi Lee

    2017-10-01

    Full Text Available Chronic low-grade inflammation plays a pivotal role in the pathogenesis of obesity, due to its associated chronic diseases such as type II diabetes, cardiovascular diseases, pulmonary diseases and cancer. Thus, targeting inflammation is an attractive strategy to counter the burden of obesity-induced health problems. Recently, food-derived bioactive compounds have been spotlighted as a regulator against various chronic diseases due to their low toxicity, as opposed to drugs that induce severe side effects. Here we describe the beneficial effects of dietary anthocyanins on obesity-induced metabolic disorders and inflammation. Red cabbage microgreen, blueberry, blackcurrant, mulberry, cherry, black elderberry, black soybean, chokeberry and jaboticaba peel contain a variety of anthocyanins including cyanidins, delphinidins, malvidins, pelargonidins, peonidins and petunidins, and have been reported to alter both metabolic markers and inflammatory markers in cells, animals, and humans. This review discusses the interplay between inflammation and obesity, and their subsequent regulation via the use of dietary anthocyanins, suggesting an alternative dietary strategy to ameliorate obesity and obesity associated chronic diseases.

  2. Gut Microbiota: A Contributing Factor to Obesity

    Science.gov (United States)

    Harakeh, Steve M.; Khan, Imran; Kumosani, Taha; Barbour, Elie; Almasaudi, Saad B.; Bahijri, Suhad M.; Alfadul, Sulaiman M.; Ajabnoor, Ghada M. A.; Azhar, Esam I.

    2016-01-01

    Obesity, a global epidemic of the modern era, is a risk factor for cardiovascular diseases (CVD) and diabetes. The pervasiveness of obesity and overweight in both developed as well as developing populations is on the rise and placing a huge burden on health and economic resources. Consequently, research to control this emerging epidemic is of utmost importance. Recently, host interactions with their resident gut microbiota (GM) have been reported to be involved in the pathogenesis of many metabolic diseases, including obesity, diabetes, and CVD. Around 1014 microorganisms reside within the lower human intestine and many of these 1014 microorganisms have developed mutualistic or commensal associations with the host and actively involved in many physiological processes of the host. However, dysbiosis (altered gut microbial composition) with other predisposing genetic and environmental factors, may contribute to host metabolic disorders resulting in many ailments. Therefore, delineating the role of GM as a contributing factor to obesity is the main objective of this review. Obesity research, as a field is expanding rapidly due to major advances in nutrigenomics, metabolomics, RNA silencing, epigenetics, and other disciplines that may result in the emergence of new technologies and methods to better interpret causal relationships between microbiota and obesity. PMID:27625997

  3. Gut Microbiota: a contributing factor to obesity

    Directory of Open Access Journals (Sweden)

    Steve M Harakeh

    2016-08-01

    Full Text Available Obesity, a global epidemic of the modern era, is a risk factor for cardiovascular diseases (CVD and diabetes. The pervasiveness of obesity and overweight in both developed as well as developing populations is on the rise and placing a huge burden on health and economic resources. Consequently, research to control this emerging epidemic is of utmost importance. Recently, host interactions with their resident gut microbiota (GM have been reported to be involved in the pathogenesis of many metabolic diseases, including obesity, diabetes, and CVD. Around 1014 microorganisms reside within the lower human intestine and many of these 1014microorganisms have developed mutualistic or commensal associations with the host and actively involved in many physiological processes of the host. However, dysbiosis (altered gut microbial composition with other predisposing genetic and environmental factors, may contribute to host metabolic disorders resulting in many ailments. Therefore, delineating the role of GM as a contributing factor to obesity is the main objective of this review.Obesity research, as a field is expanding rapidly due to major advances in nutrigenomics, metabolomics, RNA silencing, epigenetics and other disciplines that may result in the emergence of new technologies and methods to better interpret causal relationships between microbiota and obesity.

  4. Gut Microbiota: A Contributing Factor to Obesity.

    Science.gov (United States)

    Harakeh, Steve M; Khan, Imran; Kumosani, Taha; Barbour, Elie; Almasaudi, Saad B; Bahijri, Suhad M; Alfadul, Sulaiman M; Ajabnoor, Ghada M A; Azhar, Esam I

    2016-01-01

    Obesity, a global epidemic of the modern era, is a risk factor for cardiovascular diseases (CVD) and diabetes. The pervasiveness of obesity and overweight in both developed as well as developing populations is on the rise and placing a huge burden on health and economic resources. Consequently, research to control this emerging epidemic is of utmost importance. Recently, host interactions with their resident gut microbiota (GM) have been reported to be involved in the pathogenesis of many metabolic diseases, including obesity, diabetes, and CVD. Around 10(14) microorganisms reside within the lower human intestine and many of these 10(14) microorganisms have developed mutualistic or commensal associations with the host and actively involved in many physiological processes of the host. However, dysbiosis (altered gut microbial composition) with other predisposing genetic and environmental factors, may contribute to host metabolic disorders resulting in many ailments. Therefore, delineating the role of GM as a contributing factor to obesity is the main objective of this review. Obesity research, as a field is expanding rapidly due to major advances in nutrigenomics, metabolomics, RNA silencing, epigenetics, and other disciplines that may result in the emergence of new technologies and methods to better interpret causal relationships between microbiota and obesity.

  5. Review shows that maternal obesity induces serious adverse neonatal effects and is associated with childhood obesity in their offspring.

    Science.gov (United States)

    Mitanchez, Delphine; Chavatte-Palmer, Pascale

    2018-02-08

    Obesity at the start of pregnancy has been rising worldwide, increasing the risk of maternal complications. We reviewed the independent effects of maternal obesity during pregnancy on neonatal adverse outcomes and the risk of childhood obesity and adverse cardio-metabolic profiles. We searched MEDLINE for papers published in English between December 2007 and November 2017, focusing primarily on human studies published in the last five years. However, we also chose to highlight examples derived from model animals that could bring mechanistic insight and preventive and therapeutic avenues. Our review showed that maternal obesity had independent effects on neonatal adverse outcomes such as macrosomia, perinatal mortality and birth defects. Maternal obesity alone increased the risks for adverse neonatal outcomes, including macrosomia, perinatal mortality, induced preterm birth and birth defects. In association with excess gestational weight gain, mainly early in pregnancy, increased the risks of childhood obesity, higher fat mass and, to a smaller extent, adverse cardio-metabolic profiles. Animal models highlighted sexually dimorphic responses to maternal obesity. Maternal obesity induced serious adverse neonatal effects and was associated with childhood obesity in their offspring. The peri-conceptional period is critical for metabolic programming, and obese women need close monitoring from conception. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  6. Hyperglycemia abolishes meal-induced satiety by a dysregulation of ghrelin and peptide YY3-36 in healthy overweight/obese humans

    DEFF Research Database (Denmark)

    Knudsen, Sine H; Karstoft, Kristian; Solomon, Thomas

    2014-01-01

    Satiety and satiety-regulating gut hormone levels are abnormal in hyperglycemic individuals. We aimed to determine whether these abnormalities are secondary to hyperglycemia. Ten healthy overweight/obese subjects (age: 56 ± 3 yr; BMI: 30.3 ± 1.2 kg/m(2)) received three equicaloric meals at t = 0, 4......, glucose, insulin, PYY3-36, and the feeling of fullness were increased in the postprandial periods, whereas ghrelin was decreased. In the hyperglycemia trial, in which plasma glucose was increased to 11.2 ± 0.1 mmol/l, postprandial meal responses (AUC: 0-2, 4-6, and 8-10 h) of PYY3-36 were lower (meal 1, P...... 0.05; meal 3, P > 0.05) were higher compared with the control trial. Furthermore, the incremental (Δ0-0.5, 4-4.5, and 8-8.5 h) ghrelin response to the first and third meals was higher in the hyperglycemia trial in contrast to control (Δ: 2.3 ± 8.0, P = 0.05; Δ: 14.4 ± 2.5, P...

  7. Marine Algae as a Potential Source for Anti-Obesity Agents

    OpenAIRE

    Wan-Loy, Chu; Siew-Moi, Phang

    2016-01-01

    Obesity is a major epidemic that poses a worldwide threat to human health, as it is also associated with metabolic syndrome, type 2 diabetes and cardiovascular disease. Therapeutic intervention through weight loss drugs, accompanied by diet and exercise, is one of the options for the treatment and management of obesity. However, the only approved anti-obesity drug currently available in the market is orlistat, a synthetic inhibitor of pancreatic lipase. Other anti-obesity drugs are still bein...

  8. Fasting Ghrelin Levels Are Decreased in Obese Subjects and Are Significantly Related With Insulin Resistance and Body Mass Index

    Directory of Open Access Journals (Sweden)

    Dimitrios Papandreou

    2017-10-01

    CONCLUSION: Obese subjects have low fasting ghrelin levels that they are significantly related to insulin resistance and body mass index. More prospective studies are needed to establish the role of ghrelin in the pathogenesis of human obesity.

  9. Overweight and Obesity (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Overweight and Obesity KidsHealth / For Parents / Overweight and Obesity ... be at risk for substance abuse How Are Overweight and Obesity Defined? Body mass index (BMI) uses ...

  10. Maternal smoking-A contributor to the obesity epidemic?

    Science.gov (United States)

    Chen, Hui; Morris, Margaret J

    2007-10-01

    The prevalence of obesity is increasing worldwide, and the rising number of obese children and adolescents is of particular concern. In humans, smoking is a predisposing factor for abdominal obesity, glucose intolerance and insulin resistance. Maternal smoking is associated with preterm birth and low birth weight. On the other hand, the incidence of obesity is higher in children and adults born of smoking mothers. Disorders in eating behaviour, reduced physical activity, and increased risk of hypertension and nicotine addiction have been observed in the offspring of smoking mothers. Evidence from animal and human studies suggests that intrauterine smoke exposure may alter peripheral and central mediators involved in the regulation of appetite and energy metabolism. Smoking cessation during pregnancy is desirable to improve health outcomes in offspring.: © Crown Copyright 2007 Published by Elsevier Ltd on behalf of Asia Oceania Assoc. for the Study of Obesity. All rights reserved.

  11. Pharmacological management of obesity in pediatric patients.

    Science.gov (United States)

    Boland, Cassie L; Harris, John Brock; Harris, Kira B

    2015-02-01

    To review current evidence of pharmacological options for managing pediatric obesity and provide potential areas for future research. A MEDLINE search (1966 to October 2014) was conducted using the following keywords: exenatide, liraglutide, lorcaserin, metformin, obesity, orlistat, pediatric, phentermine, pramlintide, topiramate, weight loss, and zonisamide. Identified articles were evaluated for inclusion, with priority given to randomized controlled trials with orlistat, metformin, glucagon-like peptide-1 agonists, topiramate, and zonisamide in human subjects and articles written in English. References were also reviewed for additional trials. Whereas lifestyle modification is considered first-line therapy for obese pediatric patients, severe obesity may benefit from pharmacotherapy. Orlistat is the only Food and Drug Administration (FDA)-approved medication for pediatric obesity and reduced body mass index (BMI) by 0.5 to 4 kg/m(2), but gastrointestinal (GI) adverse effects may limit use. Metformin has demonstrated BMI reductions of 0.17 to 1.8 kg/m(2), with mild GI adverse effects usually managed with dose titration. Exenatide reduced BMI by 1.1 to 1.7 kg/m(2) and was well-tolerated with mostly transient or mild GI adverse effects. Topiramate and zonisamide reduced weight when used in the treatment of epilepsy. Future studies should examine efficacy and safety of pharmacological agents in addition to lifestyle modifications for pediatric obesity. Lifestyle interventions remain the treatment of choice in pediatric obesity, but concomitant pharmacotherapy may be beneficial in some patients. Orlistat should be considered as second-line therapy for pediatric obesity. Evidence suggests that other diabetes and antiepileptic medications may also provide weight-loss benefits, but safety should be further evaluated. © The Author(s) 2014.

  12. Core body temperature in obesity123

    Science.gov (United States)

    Heikens, Marc J; Gorbach, Alexander M; Eden, Henry S; Savastano, David M; Chen, Kong Y; Skarulis, Monica C

    2011-01-01

    Background: A lower core body temperature set point has been suggested to be a factor that could potentially predispose humans to develop obesity. Objective: We tested the hypothesis that obese individuals have lower core temperatures than those in normal-weight individuals. Design: In study 1, nonobese [body mass index (BMI; in kg/m2) <30] and obese (BMI ≥30) adults swallowed wireless core temperature–sensing capsules, and we measured core temperatures continuously for 24 h. In study 2, normal-weight (BMI of 18–25) and obese subjects swallowed temperature-sensing capsules to measure core temperatures continuously for ≥48 h and kept activity logs. We constructed daily, 24-h core temperature profiles for analysis. Results: Mean (±SE) daily core body temperature did not differ significantly between the 35 nonobese and 46 obese subjects (36.92 ± 0.03°C compared with 36.89 ± 0.03°C; P = 0.44). Core temperature 24-h profiles did not differ significantly between 11 normal-weight and 19 obese subjects (P = 0.274). Women had a mean core body temperature ≈0.23°C greater than that of men (36.99 ± 0.03°C compared with 36.76 ± 0.03°C; P < 0.0001). Conclusions: Obesity is not generally associated with a reduced core body temperature. It may be necessary to study individuals with function-altering mutations in core temperature–regulating genes to determine whether differences in the core body temperature set point affect the regulation of human body weight. These trials were registered at clinicaltrials.gov as NCT00428987 and NCT00266500. PMID:21367952

  13. Genetics of pediatric obesity.

    Science.gov (United States)

    Manco, Melania; Dallapiccola, Bruno

    2012-07-01

    Onset of obesity has been anticipated at earlier ages, and prevalence has dramatically increased worldwide over the past decades. Epidemic obesity is mainly attributable to modern lifestyle, but family studies prove the significant role of genes in the individual's predisposition to obesity. Advances in genotyping technologies have raised great hope and expectations that genetic testing will pave the way to personalized medicine and that complex traits such as obesity will be prevented even before birth. In the presence of the pressing offer of direct-to-consumer genetic testing services from private companies to estimate the individual's risk for complex phenotypes including obesity, the present review offers pediatricians an update of the state of the art on genomics obesity in childhood. Discrepancies with respect to genomics of adult obesity are discussed. After an appraisal of findings from genome-wide association studies in pediatric populations, the rare variant-common disease hypothesis, the theoretical soil for next-generation sequencing techniques, is discussed as opposite to the common disease-common variant hypothesis. Next-generation sequencing techniques are expected to fill the gap of "missing heritability" of obesity, identifying rare variants associated with the trait and clarifying the role of epigenetics in its heritability. Pediatric obesity emerges as a complex phenotype, modulated by unique gene-environment interactions that occur in periods of life and are "permissive" for the programming of adult obesity. With the advent of next-generation sequencing techniques and advances in the field of exposomics, sensitive and specific tools to predict the obesity risk as early as possible are the challenge for the next decade.

  14. Childhood Obesity and the Right to Health

    DEFF Research Database (Denmark)

    Ó Cathaoir, Katharina Eva

    2016-01-01

    on the CRC with a more systematic basis for advising and assessing preventive measures taken by states. Moreover, while the interim report envisages a central role for states in childhood obesity prevention, it pays inadequate attention to their obligations under international human rights law. It is hoped...

  15. Refeeding hypertension in dietary obesity

    International Nuclear Information System (INIS)

    Ernsberger, P.; Nelson, D.O.

    1988-01-01

    A novel model of nutritionally induced hypertension in the rat is described. Dietary obesity was produced by providing sweet milk in addition to regular chow, which elicited a 52% increase in caloric intake. Despite 54% greater body weight gain and 139% heavier retroperitoneal fat pads, 120 days of overfeeding failed to increase systolic pressure in the conscious state or mean arterial pressure under urethan anesthesia. In contrast, mild hypertension developed in intermittantly fasted obese animals. The first 4-day supplemented fast was initiated 4 wk after the introduction of sweet milk, when the animals were 47 g overweight relative to chow-fed controls. Thereafter, 4 days of starvation were alternated with 2 wk of refeeding for a total of 4 cycles. A rapid fall in systolic blood pressure accompanied the onset of supplemented fasting and was maintained thereafter. With refeeding, blood pressure rose precipitously, despite poststarvation anorexia. Blood pressure tended to rise slightly over the remainder of the realimentation period. After the 4th supplemented fast, hypertension was sustained during 30 days of refeeding. Cumulative caloric intake in starved-refed rats fell within 2% of that in chow-fed controls. Refeeding hypertension appeared to be due to increased sympathetic nervous activity, since (1) cardiac β-adrenergic receptors were downregulated, as indicated by a 40% decrease in the maximum binding of [ 3 H]dihydroalpranolol; and (2) the decrease in heart rate as a result of β-blockade was enhanced. Refeeding hypertension in the dietary obese rat may be a potential animal model for some forms of human obesity-related hypertension

  16. Comparison of the gut microbiota composition between obese and non-obese individuals in a Japanese population, as analyzed by terminal restriction fragment length polymorphism and next-generation sequencing.

    Science.gov (United States)

    Kasai, Chika; Sugimoto, Kazushi; Moritani, Isao; Tanaka, Junichiro; Oya, Yumi; Inoue, Hidekazu; Tameda, Masahiko; Shiraki, Katsuya; Ito, Masaaki; Takei, Yoshiyuki; Takase, Kojiro

    2015-08-11

    Obesity has become one of the most serious social problems in developed countries, including Japan. The relationship between the gut microbiota and obesity has recently attracted the attention of many researchers. Although the gut microbiota was long thought to contribute to obesity, the exact association remains largely unknown. We examined the human gut microbiota composition in a Japanese population in order to determine its relationship to obesity. Stool samples from 23 non-obese subjects (body mass index [BMI] gut microbiota compositions and that certain bacterial species were significantly associated with each group (obese: Blautia hydrogenotorophica, Coprococcus catus, Eubacterium ventriosum, Ruminococcus bromii, Ruminococcus obeum; non-obese: Bacteroides faecichinchillae, Bacteroides thetaiotaomicron, Blautia wexlerae, Clostridium bolteae, Flavonifractor plautii). Gut microbial properties differ between obese and non-obese subjects in Japan, suggesting that gut microbiota composition is related to obesity.

  17. Maternal obesity in Europe

    DEFF Research Database (Denmark)

    Devlieger, Roland; Benhalima, Katrien; Damm, Peter

    2016-01-01

    , the prevalence of maternal obesity varies from 7 to 25% and seems strongly related to social and educational inequalities. Obesity during pregnancy represents an important preventable risk factor for adverse pregnancy outcomes and is associated with negative long-term health outcomes for both mothers...

  18. The Obesity Epidemic

    Centers for Disease Control (CDC) Podcasts

    2011-07-18

    Learn about obesity and the community initiatives taking place to prevent and reduce this epidemic.  Created: 7/18/2011 by National Center for Chronic Disease Prevention and Health Promotion, Division of Nutrition, Physical Activity and Obesity.   Date Released: 7/18/2011.

  19. Carbohydrate intake and obesity

    NARCIS (Netherlands)

    van Dam, R.M.; Seidell, J.C.

    2007-01-01

    The prevalence of obesity has increased rapidly worldwide and the importance of considering the role of diet in the prevention and treatment of obesity is widely acknowledged. This paper reviews data on the effects of dietary carbohydrates on body fatness. Does the composition of the diet as related

  20. Obesity Treatment Strategies

    Directory of Open Access Journals (Sweden)

    Simona Ianosi Edith

    2015-12-01

    Full Text Available Obesity is a disease with severe health consequences and increased risk of mortality. The most commonly used criteria to assess the presence and the severity of obesity are body mass index, waist circumference, waist-to-height ratio and the presence of the health conditions caused or worsened by obesity. Worldwide obesity has more than doubled in the last 4 decades. Obesity is the second of the leading preventable causes of death worldwide (after smoking. Obesity has a plurifactorial pathogenesis. The central perturbation consists in the imbalance between calories intake and calories consumption (by inappropriate diet and sedentary lifestyle. Identification of all the ethiological factors is important for treatment and prophylaxis. Weight loss benefits are multiple and important: improvement in glicemic control and in plasma lipid levels, blood presure control, obstructiv sleep apneea reduction, improvement in management of daily activities and profesional performances, increase quality of life, reduction in mortality. Overweight or obese patient will complete a diagnostic and a treatment program. Treatment of obesity claims a targeted multidimensional therapy: weight and lifestyle management, diet, sustained physical activity in daily life, exercise, decrease life stressors, smoking cessation, drug therapy, bariatric surgery psichological, familial and social suport. Weight loss program must be carefully planned, adapted to the patient’s abilities and comorbidities and supervised by a nutritionist and a physiotherapist.

  1. Obesity and the Elderly

    NARCIS (Netherlands)

    Mathus-Vliegen, Elisabeth M. H.

    2012-01-01

    The prevalence of obesity is rising progressively, even among older age groups. By the year 2030 to 2035 over 20% of the adult US population and over 25% of the Europeans will be aged 65 years or older. The predicted prevalence of obesity in Americans, 60 years and older was 37% in 2010. The

  2. Treatment of childhood obesity.

    Science.gov (United States)

    Uli, Naveen; Sundararajan, Sumana; Cuttler, Leona

    2008-02-01

    To provide an overview of treatments for childhood obesity, highlighting recent advances and recommendations. The three main treatment modalities are lifestyle interventions, medications, and bariatric surgery. Recent data support the short-term effectiveness of lifestyle interventions, and show that continued behavioral intervention increases the likelihood of a sustained effect for up to 2 years. New studies and regulatory decisions on medications for obesity (including orlistat, sibutramine, and metformin) are discussed. Emerging data suggest substantial weight loss after bariatric surgery in morbidly obese adolescents but also indicate adverse effects. An expert panel recently provided guidelines that alter definitions of obesity and offer a framework for obesity management. These guidelines are compared with others, and integrated recommendations presented. While primary prevention of childhood obesity is important, broadly effective methods to do so are not yet available. Given the large population of obese children and the risks they face, an emphasis on treatment is also critical. We suggest a staged approach, emphasizing early intervention and lifestyle changes. We also suggest limiting bariatric surgery to selected adolescents in Institutional Review Board-approved research studies. Health-policy interventions can facilitate both prevention and treatment of childhood obesity.

  3. Androgens and obesity.

    Science.gov (United States)

    Allan, Carolyn A; McLachlan, Robert I

    2010-06-01

    As testosterone levels are frequently reduced in obesity, an understanding of the relationship between serum testosterone and adiposity is necessary in the clinical evaluation of these men, in particular when considering testosterone therapy. Population and interventional data suggest a bi-directional relationship exists between testosterone and obesity in men, with lower total testosterone and sex hormone binding globulin (SHBG) (and to a lesser extent free testosterone) levels than their nonobese peers; obesity having an impact at least as important as ageing. Abnormalities in the hypothalamo-pituitary-testicular axis are seen with increasing obesity. Weight loss in massive obesity increases testosterone levels but its role in mild-moderate obesity is unclear. Testosterone supplementation reduces total body fat in hypogonadal and ageing men although the effects on regional fat distribution are less well described. Favourable changes in total body fat and regional fat distribution suggest a potential role for testosterone in obesity. However, lifestyle advice to achieve sustained weight loss should be the mainstay of management. Obese men with confirmed androgen deficiency can be offered treatment, whereas in those with low-normal testosterone levels more research is needed.

  4. Endocrine system and obesity.

    Science.gov (United States)

    Ashburn, Doyle D; Reed, Mary Jane

    2010-10-01

    Obesity is associated with significant alterations in endocrine function. An association with type 2 diabetes mellitus and dyslipidemia has been well documented. This article highlights the complexities of treating endocrine system disorders in obese patients. Copyright © 2010. Published by Elsevier Inc.

  5. Sedentary behaviour and obesity.

    Science.gov (United States)

    Shields, Margot; Tremblay, Mark S

    2008-06-01

    This article examines sedentary behaviours (television viewing, computer use and reading) in relation to obesity among Canadian adults aged 20 to 64 years. The analysis is based on 42,612 respondents from the 2007 Canadian Community Health Survey Cross-tabulations were used to compare the prevalence of obesity by time engaged in sedentary behaviours. Multiple logistic regression models were used to determine if associations between sedentary behaviours and obesity were independent of the effects of sociodemographic variables, leisure-time physical activity and diet. Approximately one-quarter of men (25%) and women (24%) who reported watching television 21 or more hours per week were classified as obese. The prevalence of obesity was substantially lower for those who averaged 5 or fewer hours of television per week (14% of men and 11% of women). When examined in multivariate models controlling for leisure-time physical activity and diet, the associations between time spent watching television and obesity persisted for both sexes. Frequent computer users (11 or more hours per week) of both sexes had increased odds of obesity, compared with those who used computers for 5 or fewer hours per week. Time spent reading was not related to obesity.

  6. Obesity: A Bibliographic Review

    Science.gov (United States)

    McGowan, Beth

    2012-01-01

    The study of obesity is a relatively new interdisciplinary academic field. The community college library shelves should contain two types of resources. First, several kinds of reference materials, and second, a host of broader materials that place the discussion of obesity within a cultural framework. This overview is divided into two major…

  7. Severe childhood obesity matters

    NARCIS (Netherlands)

    Slootweg, O.H.

    2014-01-01

    To date, obesity represents a major public health challenge. Obesity is at any age a concern but in pediatric populations it is particularly alarming because of its immediate biomedical and psychosocial consequences and the expectation that it will lead to an increase in morbidity and mortality and

  8. Obesity and asthma

    DEFF Research Database (Denmark)

    Ali, Zarqa; Ulrik, Charlotte Suppli

    2013-01-01

    Epidemiological data has established increasing adiposity as a risk factor for incident asthma. However, the mechanisms underlying the association between obesity and asthma are incompletely understood. In the present paper, we review current knowledge of possible mechanisms mediating the observed...... association between obesity and asthma....

  9. The genetics of obesity.

    Science.gov (United States)

    All definitions of the metabolic syndrome include some form of obesity as one of the possible features. Body mass index (BMI) has a known genetic component, currently estimated to account for about 70% of the population variance in weight status for non-syndromal obesity. Much research effort has be...

  10. [Obesity and colorectal cancer].

    Science.gov (United States)

    Na, Soo-Young; Myung, Seung-Jae

    2012-01-01

    Obesity worldwide is constantly increasing. Obesity acts as an independent significant risk factor for malignant tumors of various organs including colorectal cancer. Visceral adipose tissue is physiologically more important than subcutaneous adipose tissue. The relative risk of colorectal cancer of obese patients is about 1.5 times higher than the normal-weight individuals, and obesity is also associated with premalignant colorectal adenoma. The colorectal cancer incidence of obese patients has gender-specific and site-specific characteristics that it is higher in men than women and in the colon than rectum. Obesity acts as a risk factor of colorectal carcinogenesis by several mechanisms. Isulin, insulin-like growth factor, leptin, adiponectin, microbiome, and cytokines of chronic inflammation etc. have been understood as its potential mechanisms. In addition, obesity in patients with colorectal cancer negatively affects the disease progression and response of chemotherapy. Although the evidence is not clear yet, there are some reports that weight loss as well as life-modification such as dietary change and physical activity can reduce the risk of colorectal cancer. It is very important knowledge in the point that obesity is a potentially modifiable risk factor that can alter the incidence and outcome of the colorectal cancer.

  11. Updates on obesity pharmacotherapy.

    Science.gov (United States)

    Velazquez, Amanda; Apovian, Caroline M

    2018-01-01

    Obesity is a chronic, relapsing disease that necessitates a multidisciplinary approach to management. Behavioral changes are the foundation to management, but adjunctive therapy is often warranted, including pharmacologic therapies and/or bariatric surgery. Until recently, treatment options included only short-term therapy (≤12 weeks), and paths beyond that schedule were challenging, as knowledge of the biology of obesity was lacking. With increased recognition of obesity as a chronic, complex medical disease, newer agents have been approved as long-term therapy, and the cornerstone of treatment is chronic behavior and lifestyle change. In the last decade, the Food and Drug Administration (FDA) has approved several new weight loss medications for the chronic management of obesity. In this review paper, we provide the latest updates on obesity pharmacotherapy. The main areas we will cover include (1) pharmacological management of obesity, (2) a review of FDA-approved weight loss medications, (3) comanagement of obesity and its metabolic sequelae (type 2 diabetes mellitus, hypertension, and dyslipidemia), and (4) obesity-centric prescribing for mental illness, neurological disorders, and contraceptive planning. © 2018 New York Academy of Sciences.

  12. Pharmacological management of obesity.

    Science.gov (United States)

    Velazquez, Amanda; Apovian, Caroline M

    2017-04-28

    Current management of obesity includes three main arms: behavioral modification, pharmacologic therapy, and bariatric surgery. Decades prior, the only pharmacological agents available to treat obesity were approved only for short-term use (≤ 12 weeks) by the Food and Drug Administration (FDA). However, in the last several years, the FDA has approved several medications for longer term treatment of obesity. This highlights the important progression that we, as a society, better appreciate now the chronicity and complexity of obesity as a disease. Also, availability of more medication options gives healthcare providers more possibilities to consider in the management of obesity. Medications for obesity can be simply categorized as FDA approved short-term use (diethylproprion, phendimetrazine, benzphetamine, and phentermine) and long-term use (orlistat, phentermine/topiramate ER, lorcaserin, naltrexone/bupropion ER and liraglutide). Additionally, type 2 diabetes (T2DM) is commonly seen in patients with obesity and necessitates consideration of pharmacological options that do not hinder patients' weight loss. Finally, weight-centric prescribing is also an important component to pharmacological management of obesity. It warrants that healthcare providers thoroughly review their patients' medication lists to determine if any of these agents could be contributing to weight gain.

  13. Obesity and Dyslipidemia

    NARCIS (Netherlands)

    Franssen, Remco; Monajemi, Houshang; Stroes, Erik S. G.; Kastelein, John J. P.

    2008-01-01

    The alarming and still increasing prevalence of obesity and associated cardiovascular risk raises much concern. The increase in cardiovascular risk depends to a significant extent on the changes in lipid profiles as observed in obesity These changes are decreased high-density lipoprotein cholesterol

  14. Epidemiology of obesity

    NARCIS (Netherlands)

    Seidell, Jacob C

    The prevalence of obesity is increasing at an alarming rate in many parts of the world. In White populations living in the west and north of Europe, Australia, and the United States, the prevalence of obesity is similarly high in men and women. In countries with relatively low gross national

  15. Canine and feline obesity

    DEFF Research Database (Denmark)

    Sandøe, Peter; Palmer, Clare; Corr, Sandra

    2014-01-01

    Recent years have seen a drastic increase in the rates of overweight and obesity among people living in some developed nations. There has also been increased concern over obesity in companion animals. In the latest article in Veterinary Record's series on One Health, Peter Sandøe and colleagues...

  16. Modeling Diet-Induced Obesity with Obesity-Prone Rats: Implications for Studies in Females.

    Directory of Open Access Journals (Sweden)

    Erin D Giles

    2016-11-01

    Full Text Available Obesity is a worldwide epidemic, and the comorbidities associated with obesity are numerous. Over the last two decades, we and others have employed an outbred rat model to study the development and persistence of obesity, as well as the metabolic complications that accompany excess weight. In this review, we summarize the strengths and limitations of this model and how it has been applied to further our understanding of human physiology in the context of weight loss and weight regain. We also discuss how the approach has been adapted over time for studies in females and female-specific physiological conditions, such as menopause and breast cancer. As excess weight and the accompanying metabolic complications have become common place in our society, we expect that this model will continue to provide a valuable translational tool to establish physiological relevant connections to the basic science studies of obesity and body weight regulation.

  17. DNA methylation in obesity

    Directory of Open Access Journals (Sweden)

    Małgorzata Pokrywka

    2014-11-01

    Full Text Available The number of overweight and obese people is increasing at an alarming rate, especially in the developed and developing countries. Obesity is a major risk factor for diabetes, cardiovascular disease, and cancer, and in consequence for premature death. The development of obesity results from the interplay of both genetic and environmental factors, which include sedentary life style and abnormal eating habits. In the past few years a number of events accompanying obesity, affecting expression of genes which are not directly connected with the DNA base sequence (e.g. epigenetic changes, have been described. Epigenetic processes include DNA methylation, histone modifications such as acetylation, methylation, phosphorylation, ubiquitination, and sumoylation, as well as non-coding micro-RNA (miRNA synthesis. In this review, the known changes in the profile of DNA methylation as a factor affecting obesity and its complications are described.

  18. Obesity and menopause.

    Science.gov (United States)

    Al-Safi, Zain A; Polotsky, Alex J

    2015-05-01

    Over the recent decades, the prevalence of obesity in the United States has increased to epidemic proportions to more than 35% of adults, along with an increased risk of a number of health conditions, including hypertension, adverse lipid concentrations, and type 2 diabetes. The relationships between menopausal transition, weight gain, and obesity are reported but incompletely understood. The association between menopause and these measures has been the subject of many studies, along with examining their effect on reproductive hormones and menopausal symptoms. The purpose of this review is to summarize what is published in the literature on this subject and examine it through: (1) the possible impact of obesity on the timing of menopause; (2) the effect of obesity on menopausal symptoms and reproductive hormones around the time of menopause; and (3) the effect of menopause on obesity, weight gain, and body composition. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Predisposition to Obesity

    DEFF Research Database (Denmark)

    Olsen, Nanna Julie; Mortensen, Erik Lykke; Heitmann, Berit Lilienthal

    2012-01-01

    predisposed to future obesity. The purpose of this paper is to review interventions on obesity prevention published during the past year, and to examine if interventions targeting predisposed groups or individuals seem more efficient in preventing obesity than studies targeting general populations. Among 15......Obesity prevention should remain a priority, even if there is some suggestion that the epidemic may presently have reached a stable level. However, previous interventions have not been effective in preventing overweight and obesity, and at the same time studies suggest that some subgroups are more...... identified studies, 7 targeted predisposed children or adolescents. More of the studies targeting predisposed individuals were able to show significant effects than the studies targeting general populations. Most studies targeting predisposed defined the predisposition based on ethnicity or socioeconomic...

  20. Obesity in pregnancy

    DEFF Research Database (Denmark)

    Nøhr, Ellen Aagaard

    Background: The obesity epidemic has led to an increase in obese women of childbearing age. This gives cause for concern because prepregnancy obesity is associated with a number of adverse pregnancy outcomes. The newly established Danish National Birth Cohort (DNBC) has a size that permits...... an investigation of the association between maternal obesity and rare, but important outcomes, for which more insight is needed, such as fetal death, subtypes of preterm birth, and neonatal mortality. The low participation rate of 30% to the DNBC may, however, raise new questions related to the validity...... of the findings, so we also carried out a study of the consequences of this selection on the estimates of relative risk.Studies of maternal obesity: Within the DNBC we examined the association between prepregnancy body mass index (BMI) and the risk of fetal death (n=54,505), subtypes of preterm birth (n=62...

  1. Obesity and Asthma

    DEFF Research Database (Denmark)

    Juel, Caroline Trunk-Black; Ulrik, Charlotte Suppli

    2013-01-01

    Asthma is more prevalent in obese compared with normal weight subjects. Our aim has been to review current knowledge of the impact of obesity on asthma severity, asthma control, and response to therapy.Several studies have shown that overweight and obesity is associated with more severe asthma...... and impaired quality of life compared with normal weight individuals. Furthermore, obesity is associated with poorer asthma control, as assessed by asthma control questionnaires, limitations in daily activities, breathlessness and wheezing, use of rescue medication, unscheduled doctor visits, emergency...... department visits, and hospitalizations for acute asthma. Studies of the impact of a high body mass index (BMI) on response to asthma therapy have, however, revealed conflicting results. Most studies show that overweight and obesity is associated with less favorable response to asthma therapy with regard...

  2. Asthma and obesity

    DEFF Research Database (Denmark)

    Ulrik, Charlotte S

    2016-01-01

    PURPOSE OF REVIEW: Obesity has significant negative impact on asthma control and risk of exacerbations. The purpose of this review is to discuss recent studies evaluating the effects of weight reduction on asthma control in obese adults. RECENT FINDINGS: Clinical studies have shown that weight...... reduction in obese patients is associated with improvements in symptoms, use of controller medication, and asthma-related quality of life together with a reduction in the risk for severe exacerbations. Furthermore, several studies have also revealed improvements in lung function and airway responsiveness...... reduction in obese adults with asthma leads to an overall improvement in asthma control, including airway hyperresponsiveness and inflammation. Weight reduction should be a cornerstone in the management of obese patients with asthma....

  3. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non obese humans

    Science.gov (United States)

    Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-cen...

  4. Fibroblast growth factor 21 is elevated in metabolically unhealthy obesity and affects lipid deposition, adipogenesis, and adipokine secretion of human abdominal subcutaneous adipocytes

    Directory of Open Access Journals (Sweden)

    Lucia Berti

    2015-07-01

    Conclusions: The hepatokine FGF21 exerts weak lipogenic and anti-adipogenic actions and marked adiponectin-suppressive and leptin and interleukin-6 release-promoting effects in human differentiating preadipocytes. Together with the higher serum concentrations in MUHO subjects, our findings reveal FGF21 as a circulating factor promoting the development of metabolically unhealthy adipocytes.

  5. Economic Growth, Climate Change, and Obesity.

    Science.gov (United States)

    Minos, Dimitrios; Butzlaff, Iris; Demmler, Kathrin Maria; Rischke, Ramona

    2016-12-01

    Human and planetary health as well as economic growth are firmly interlinked and subject to complex interaction effects. In this paper, we provide an overview of interlinkages between economic growth, climate change, and obesity focusing on recent advances in the literature. In addition to empirical findings, we discuss different theoretical frameworks used to conceptualize these complex links and highlight policy options and challenges. We conclude that policies addressing both climate change and obesity simultaneously are particularly promising and often suitable for ensuring sustainable development.

  6. OBESITY-INDUCED HYPERTENSION: INTERACTION OF NEUROHUMORAL AND RENAL MECHANISMS

    Science.gov (United States)

    Hall, John E.; do Carmo, Jussara M.; da Silva, Alexandre A.; Wang, Zhen; Hall, Michael E.

    2015-01-01

    Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65–75% of the risk for human primary (essential) hypertension. Increased renal tubular sodium reabsorption impairs pressure natriuresis and plays an important role in initiating obesity hypertension. The mediators of abnormal kidney function and increased blood pressure during development of obesity hypertension include 1) physical compression of the kidneys by fat in and around the kidneys, 2) activation of the renin-angiotensin-aldosterone system (RAAS), and 3) increased sympathetic nervous system (SNS) activity. Activation of the RAAS system is likely due, in part, to renal compression as well as SNS activation. However, obesity also causes mineralocorticoid receptor activation independent of aldosterone or angiotensin II. The mechanisms for SNS activation in obesity have not been fully elucidated but appear to require leptin and activation of the brain melanocortin system. With prolonged obesity and development of target organ injury, especially renal injury, obesity-associated hypertension becomes more difficult to control, often requiring multiple antihypertensive drugs and treatment of other risk factors, including dyslipidemia, insulin resistance and diabetes, and inflammation. Unless effective anti-obesity drugs are developed, the impact of obesity on hypertension and related cardiovascular, renal and metabolic disorders is likely to become even more important in the future as the prevalence of obesity continues to increase. PMID:25767285

  7. The role of leptin in human lipid and glucose metabolism: the effects of acute recombinant human leptin infusion in young healthy males

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2011-01-01

    Obese and lean humans treated with leptin have not experienced convincing weight-loss results compared with the dramatic weight losses observed in obese rodents.......Obese and lean humans treated with leptin have not experienced convincing weight-loss results compared with the dramatic weight losses observed in obese rodents....

  8. Defective regulation of adipose tissue autophagy in obesity.

    Science.gov (United States)

    Nuñez, C E; Rodrigues, V S; Gomes, F S; Moura, R F de; Victorio, S C; Bombassaro, B; Chaim, E A; Pareja, J C; Geloneze, B; Velloso, L A; Araujo, E P

    2013-11-01

    Autophagy is a highly regulated process that has an important role in the control of a wide range of cellular functions, such as organelle recycling, nutrient availability and tissue differentiation. A recent study has shown an increased autophagic activity in the adipose tissue of obese subjects, and a role for autophagy in obesity-associated insulin resistance was proposed. Body mass reduction is the most efficient approach to tackle insulin resistance in over-weight subjects; however, the impact of weight loss in adipose tissue autophagy is unknown. Adipose tissue autophagy was evaluated in mice and humans. First, a mouse model of diet-induced obesity and diabetes was maintained on a 15-day, 40% caloric restriction. At baseline, markers of autophagy were increased in obese mice as compared with lean controls. Upon caloric restriction, autophagy increased in the lean mice, whereas it decreased in the obese mice. The reintroduction of ad libitum feeding was sufficient to rapidly reduce autophagy in the lean mice and increase autophagy in the obese mice. In the second part of the study, autophagy was evaluated in the subcutaneous adipose tissue of nine obese-non-diabetic and six obese-diabetic subjects undergoing bariatric surgery for body mass reduction. Specimens were collected during the surgery and approximately 1 year later. Markers of systemic inflammation, such as tumor necrosis factor-1α, interleukin (IL)-6 and IL-1β were evaluated. As in the mouse model, human obesity was associated with increased autophagy, and body mass reduction led to an attenuation of autophagy in the adipose tissue. Obesity and caloric overfeeding are associated with the defective regulation of autophagy in the adipose tissue. The studies in obese-diabetic subjects undergoing improved metabolic control following calorie restriction suggest that autophagy and inflammation are regulated independently.

  9. Carotenoids in Adipose Tissue Biology and Obesity.

    Science.gov (United States)

    Bonet, M Luisa; Canas, Jose A; Ribot, Joan; Palou, Andreu

    2016-01-01

    Cell, animal and human studies dealing with carotenoids and carotenoid derivatives as nutritional regulators of adipose tissue biology with implications for the etiology and management of obesity and obesity-related metabolic diseases are reviewed. Most studied carotenoids in this context are β-carotene, cryptoxanthin, astaxanthin and fucoxanthin, together with β-carotene-derived retinoids and some other apocarotenoids. Studies indicate an impact of these compounds on essential aspects of adipose tissue biology including the control of adipocyte differentiation (adipogenesis), adipocyte metabolism, oxidative stress and the production of adipose tissue-derived regulatory signals and inflammatory mediators. Specific carotenoids and carotenoid derivatives restrain adipogenesis and adipocyte hypertrophy while enhancing fat oxidation and energy dissipation in brown and white adipocytes, and counteract obesity in animal models. Intake, blood levels and adipocyte content of carotenoids are reduced in human obesity. Specifically designed human intervention studies in the field, though still sparse, indicate a beneficial effect of carotenoid supplementation in the accrual of abdominal adiposity. In summary, studies support a role of specific carotenoids and carotenoid derivatives in the prevention of excess adiposity, and suggest that carotenoid requirements may be dependent on body composition.

  10. Development and standardization of radioimmunoassay technique for human proinsulin determining and its use in the study of type II diabetes mellitus associated to obesity

    International Nuclear Information System (INIS)

    Nascimento, Martha do

    1996-01-01

    The availability of immunoassay methodology for proinsulin is important to define its physiological and pathophysiological significance in humans. Serum concentration of proinsulin are elevated in patients with type II Diabetes Mellitus (NIDDM) and recently diagnosed Type I, so a raised circulating concentration of proinsulin may serve as an early indicator of β cells dysfunction. recently, in NIDDM the serum concentrations of proinsulin and its B-chain-C-peptide junctional split form, des (31-32), were found to correlate with diastolic blood pressure, a risk factor for cardiovascular disease. The development of a sensitive and specific radioimmunoassay (RIA) methodology for proinsulin has been difficult due to its low concentration in serum and the presence of proinsulin conversion intermediates in fluids and tissues. Also other potentially cross-reactive peptides, including insulin and C-peptide, can interfere in the assay. This work describe a highly specific human proinsulin RIA developed by using biosynthetic human proinsulin (hPI) as immunogen, standard and tracer. (author)

  11. Manikin families representing obese airline passengers in the US.

    Science.gov (United States)

    Park, Hanjun; Park, Woojin; Kim, Yongkang

    2014-01-01

    Aircraft passenger spaces designed without proper anthropometric analyses can create serious problems for obese passengers, including: possible denial of boarding, excessive body pressures and contact stresses, postural fixity and related health hazards, and increased risks of emergency evacuation failure. In order to help address the obese passenger's accommodation issues, this study developed male and female manikin families that represent obese US airline passengers. Anthropometric data of obese individuals obtained from the CAESAR anthropometric database were analyzed through PCA-based factor analyses. For each gender, a 99% enclosure cuboid was constructed, and a small set of manikins was defined on the basis of each enclosure cuboid. Digital human models (articulated human figures) representing the manikins were created using a human CAD software program. The manikin families were utilized to develop design recommendations for selected aircraft seat dimensions. The manikin families presented in this study would greatly facilitate anthropometrically accommodating large airline passengers.

  12. Dietary strawberries increase proliferative response of CD3/CD28-activated CD8+ T cells and production of TNF-alpha in lipopolysaccharide-stimulated monocytes from obese human subjects

    Science.gov (United States)

    Obesity increases the risk of developing bacterial and viral infections compared to normal weight. In a 7 wk double-blind, randomized, crossover trial, twenty obese volunteers (20-50 y old, BMI between 30-40 kg/m2) were fed freeze-dried strawberry powder or strawberry-flavored placebo preparations ...

  13. Obesity and Pregnancy

    Directory of Open Access Journals (Sweden)

    Serap Ejder Apay

    2009-08-01

    Full Text Available Obesity; a state of being 20% over one’s normal weight due to excessive fat; that is, it is defined as the accumulation of too much fat in the body. The rate of obesity in the world has elevated. In the last two decades, it is considered that there have been increases in the rates of the obesity with changes in the socio-economic state and nutritional habits in Turkey as well as in modern western countries. The increase of the obesity is a matter of concern but the aspect which is much more matter of concern is in the increase of obesity in women at the reproductive age or gradually increasing rate of being overweight. If the pregnant woman is obese, most of the physiological changes occurring during pregnancy may be various. During their childbearing years, obese women are at an increased risk for pregnancy-induced hypertension, gestational diabetes, labour induction, caesareans births, and failed vaginal birth following to caesarean. Nurses should have the knowledge to adapt the care they provide according to this knowledge and encourage the pregnant women to acquire behaviours which will improve their health. [TAF Prev Med Bull 2009; 8(4.000: 345-350

  14. Testosterone and obesity.

    Science.gov (United States)

    Kelly, D M; Jones, T H

    2015-07-01

    Testosterone is a key hormone in the pathology of metabolic diseases such as obesity. Low testosterone levels are associated with increased fat mass (particularly central adiposity) and reduced lean mass in males. These morphological features are linked to metabolic dysfunction, and testosterone deficiency is associated with energy imbalance, impaired glucose control, reduced insulin sensitivity and dyslipidaemia. A bidirectional relationship between testosterone and obesity underpins this association indicated by the hypogonadal-obesity cycle and evidence weight loss can lead to increased testosterone levels. Androgenic effects on enzymatic pathways of fatty acid metabolism, glucose control and energy utilization are apparent and often tissue specific with differential effects noted in different regional fat depots, muscle and liver to potentially explain the mechanisms of testosterone action. Testosterone replacement therapy demonstrates beneficial effects on measures of obesity that are partially explained by both direct metabolic actions on adipose and muscle and also potentially by increasing motivation, vigour and energy allowing obese individuals to engage in more active lifestyles. The degree of these beneficial effects may be dependent on the treatment modality with longer term administration often achieving greater improvements. Testosterone replacement may therefore potentially be an effective adjunctive treatment for weight management in obese men with concomitant hypogonadism. © 2015 World Obesity.

  15. Underestimation of Adolescent Obesity

    Science.gov (United States)

    Buttenheim, Alison M.; Gol, Noreen; Pebley, Anne R.

    2014-01-01

    Background Previous studies assessing the validity of adolescent self-reported height and weight for estimating obesity prevalence have not accounted for potential bias due to non-response in self-reports. Objectives The purpose of this study was to assess the implications of selective non-response in self-reports of height and weight for estimates of adolescent obesity. Methods The authors analyzed 613 adolescents ages 12-17 from the 2006-08 Los Angeles Family and Neighborhood Survey, a longitudinal study of Los Angeles County households with an oversample of poor neighborhoods. Obesity prevalence estimates based on (1) self-report, (2) measured height and weight for those who did report, and (3) measured height and weight for those who did not report were compared. Results Among younger teens, measured obesity prevalence was higher for those who did not report height and weight compared to those who did (40% vs. 30). Consequently, obesity prevalence based on self-reported height and weight underestimated measured prevalence by 12 percentage points (when accounting for non-response) vs. 9 percentage points (when non-response was not accounted for). Results were robust to the choice of difference child growth references (i.e,, CDC vs. International Obesity Task Force). Discussion Adolescent obesity surveillance and prevention efforts must take into account selective non-response for self-reported height and weight, particularly for younger teens. Results should be replicated in a nationally-representative sample. PMID:23636345

  16. Obesity and blood cancers

    Directory of Open Access Journals (Sweden)

    Djordje S. Popovic

    2017-09-01

    Full Text Available Obesity is the result of excessive accumulation of adipose tissue, and positive energy balance is the dominant cause of obesity. Obesity has reached pandemic proportions and represents a major global health issue. It contributes to the development of several major illnesses, including Type 2 diabetes, cardiovascular diseases, and various types of cancer. Excessive accumulation of visceral adipose tissue results in its altered secretory function. Hyperinsulinemia, lipid disorders, and chronic inflammation follow, providing an ideal environment for the initiation and promotion of cancer. Other disorders which are characteristic of obesity, such as alterations in the function of other endocrine systems and changes in microbiota, could also contribute to the elevated cancer risk. Hematological malignancies are forms of cancer originating from hematopoietic cells including cells of the immune system. Current data suggest a causal relationship between obesity and different forms of hematological malignancies. The major mechanisms linking obesity and blood cancers include changes in the secretion of adipokines and altered insulin, insulin-like growth factor-1, and lipid signalling, as well as dyslipidemia and increased inflammatory activity. Identifying and understanding the definite pathways connecting obesity with the onset and progression of different forms of hematological malignancies could enable the implementation of various therapeutic interventions including simple dietary modifications, utilization of wellknown drugs used for other diseases (metformin, statins, and non-steroidal anti-inflammatory drugs, as well as novel drugs directed against specific cellular targets.

  17. Treatment of adolescent obesity.

    Science.gov (United States)

    Steinbeck, Katharine S; Lister, Natalie B; Gow, Megan L; Baur, Louise A

    2018-04-13

    The increased prevalence of adolescent obesity and associated short-term and long-term complications emphasize the need for effective treatment. In this Review, we aim to describe the evidence for, and elements of, behaviour management and adjunctive therapies and highlight the opportunities and challenges presented by obesity management in adolescence. The broad principles of treatment include management of obesity-associated complications; a developmentally appropriate approach; long-term behaviour modification (dietary change, increased physical activity, decreased sedentary behaviours and improved sleep patterns); long-term weight maintenance strategies; and consideration of the use of pharmacotherapy, more intensive dietary therapies and bariatric surgery. Bariatric surgery should be considered in those with severe obesity and be undertaken by skilled bariatric surgeons affiliated with teams experienced in the medical and psychosocial management of adolescents. Adolescent obesity management strategies are more reliant on active participation than those for childhood obesity and should recognize the emerging autonomy of the patient. The challenges in adolescent obesity relate primarily to the often competing demands of developing autonomy and not yet having attained neurocognitive maturity.

  18. Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention.

    Science.gov (United States)

    Liu, Ruixin; Hong, Jie; Xu, Xiaoqiang; Feng, Qiang; Zhang, Dongya; Gu, Yanyun; Shi, Juan; Zhao, Shaoqian; Liu, Wen; Wang, Xiaokai; Xia, Huihua; Liu, Zhipeng; Cui, Bin; Liang, Peiwen; Xi, Liuqing; Jin, Jiabin; Ying, Xiayang; Wang, Xiaolin; Zhao, Xinjie; Li, Wanyu; Jia, Huijue; Lan, Zhou; Li, Fengyu; Wang, Rui; Sun, Yingkai; Yang, Minglan; Shen, Yuxin; Jie, Zhuye; Li, Junhua; Chen, Xiaomin; Zhong, Huanzi; Xie, Hailiang; Zhang, Yifei; Gu, Weiqiong; Deng, Xiaxing; Shen, Baiyong; Xu, Xun; Yang, Huanming; Xu, Guowang; Bi, Yufang; Lai, Shenghan; Wang, Jian; Qi, Lu; Madsen, Lise; Wang, Jiqiu; Ning, Guang; Kristiansen, Karsten; Wang, Weiqing

    2017-07-01

    Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota.

  19. Obesity and dietary behavioural changes

    African Journals Online (AJOL)

    2010-05-31

    May 31, 2010 ... Keywords: obesity; dietary behavioural changes; weight loss; goal setting; evaluation; non-adherence; diet. Obesity: a growing concern. Obesity is complex because it is clearly a biological, psychological and social phenomenon. The increasing prevalence of obesity in many countries means that it should ...

  20. [Obesity-hypoventilation syndrome].

    Science.gov (United States)

    Weitzenblum, E; Kessler, R; Canuet, M; Chaouat, A

    2008-04-01

    The obesity-hypoventilation syndrome (OHS), or alveolar hypoventilation in the obese, has been described initially as the "Pickwickian syndrome". It is defined as chronic alveolar hypoventilation (PaO2 or =45 mmHg) in obese patients (body mass index>30 kg/m2) who have no other respiratory disease explaining the hypoxemia-hypercapnia. The large majority of obese subjects are not hypercapnic, even in case of severe obesity (>40 kg/m2). There are three principal causes, which can be associated, explaining alveolar hypoventilation in obese subjects: high cost of respiration and weakness of the respiratory muscles (probably the major cause), dysfunction of the respiratory centers with diminished chemosensitivity, long-term effects of the repeated episodes of obstructive sleep apneas observed in some patients. The role of leptin (hormone produced by adipocytes) in the pathogenesis of this syndrome, has been recently advocated. OHS is generally observed in subjects over 50 years. Its prevalence has markedly increased in recent years, probably due to the present "epidemic" of obesity. The diagnosis is often made after an episode of severe respiratory failure. Comorbidities, favored by obesity, are very frequent: systemic hypertension, left heart diseases, diabetes. OHS must be distinguished from obstructive sleep apnea syndrome (OSAS) even if the two conditions are often associated. OSAS may be absent in certain patients with OHS (20% of the patients in our experience). On the other hand obesity may be absent in certain patients with OSAS. Losing weight is the "ideal" treatment of OHS but in fact it cannot be obtained in most patients. Nocturnal ventilation (continuous positive airway pressure and mainly bilevel non invasive ventilation) is presently the best treatment of OHS and excellent short and long-term results on symptoms and arterial blood gases have been recently reported.

  1. The macrophage switch in obesity development

    Directory of Open Access Journals (Sweden)

    Angela eCastoldi

    2016-01-01

    Full Text Available Immune cell infiltration in (white adipose tissue during obesity is associated with the development of insulin resistance. In adipose tissue, the main population of leukocytes are macrophages. Macrophages can be classified into two major populations: M1, classically activated macrophages, and M2, alternatively activated macrophages, although recent studies have identified a broad range of macrophage subsets. During obesity, adipose tissue M1 macrophage numbers increase and correlate with adipose tissue inflammation and insulin resistance. Upon activation, pro-inflammatory M1 macrophages induce aerobic glycolysis. By contrast, in lean humans and mice, the number of M2 macrophages predominates. M2 macrophages secrete anti-inflammatory cytokines and utilize oxidative metabolism to maintain adipose tissue homeostasis. Here we review the immunologic and metabolic functions of adipose tissue macrophages and their different facets in obesity and the metabolic syndrome.

  2. Obesity and androgens: facts and perspectives.

    Science.gov (United States)

    Pasquali, Renato

    2006-05-01

    This review discusses androgen status in male and female obesity, according to their specific phenotype, and the main mechanisms responsible. Published data in the literature of the last 20 years represented the basis of most of the data and concepts incorporated in the review. Obesity is associated with profound alterations in androgen secretion, transport, metabolism, and action, according to a dichotomous behavior depending on sex. Obese men are characterized by a progressive decrease of testosterone levels with increasing body weight, whereas obese women, particularly those with the abdominal phenotype, tend to develop a condition of functional hyperandrogenism. Reduced sex hormone-binding globulin synthesis and circulating blood levels represent the sole common mechanism which is responsible in both sexes. Among other still partially undefined factors, mechanisms potentially responsible for the sex dichotomy in androgen levels involve specific alterations of gonadotropin secretion, estrogens, the hypothalamic-pituitary-adrenal axis, leptin, androgen receptors, specific steroidogenic enzymes in the peripheral tissues, and, possibly, ghrelin. In both sexes, androgens play an important role in determining the sex-dependent pattern of body fat distribution. Moreover there are theoretical possibilities that low testosterone in men and high free testosterone fraction in women may play a role in the development of the metabolic syndrome. This is exemplified by the well defined association between obesity and other features of the metabolic syndrome in women with polycystic ovary syndrome and in hypogonadal men. The effects of androgen and antiandrogens in obese men and women also represent arguments in favor of this association. Given the fundamental role of sex hormones in the regulation of body composition, fuel homeostasis, and reproduction in humans, more emphasis should be placed on the potential role of androgen dysregulation in the pathophysiology of different

  3. Monomeric tartrate resistant acid phosphatase induces insulin sensitive obesity.

    Directory of Open Access Journals (Sweden)

    Pernilla Lång

    2008-03-01

    Full Text Available Obesity is associated with macrophage infiltration of adipose tissue, which may link adipose inflammation to insulin resistance. However, the impact of inflammatory cells in the pathophysiology of obesity remains unclear. Tartrate resistant acid phosphatase (TRAP is an enzyme expressed by subsets of macrophages and osteoclasts that exists either as an enzymatically inactive monomer or as an active, proteolytically processed dimer.Using mice over expressing TRAP, we show that over-expression of monomeric, but not the dimeric form in adipose tissue leads to early onset spontaneous hyperplastic obesity i.e. many small fat cells. In vitro, recombinant monomeric, but not proteolytically processed TRAP induced proliferation and differentiation of mouse and human adipocyte precursor cells. In humans, monomeric TRAP was highly expressed in the adipose tissue of obese individuals. In both the mouse model and in the obese humans the source of TRAP in adipose tissue was macrophages. In addition, the obese TRAP over expressing mice exhibited signs of a low-grade inflammatory reaction in adipose tissue without evidence of abnormal adipocyte lipolysis, lipogenesis or insulin sensitivity.Monomeric TRAP, most likely secreted from adipose tissue macrophages, induces hyperplastic obesity with normal adipocyte lipid metabolism and insulin sensitivity.

  4. Role of taurine in the pathogenesis of obesity.

    Science.gov (United States)

    Murakami, Shigeru

    2015-07-01

    Taurine is a sulfur-containing amino acid that is present in mammalian tissues in millimolar concentrations. Taurine is involved in a diverse array of biological and physiological functions, including bile salt conjugation, osmoregulation, membrane stabilization, calcium modulation, anti-oxidation, and immunomodulation. The prevalence of obesity and being overweight continues to rise worldwide at an alarming rate. Obesity is associated with a higher risk of metabolic and cardiovascular diseases, cancer, and other clinical conditions. Ingestion of taurine has been shown to alleviate metabolic diseases such as hyperlipidemia, diabetes, hypertension, and obesity in animal models. A global epidemiological survey showed that 24-h urinary taurine excretion, as a marker of dietary taurine intake, was inversely associated with BMI, blood pressure, and plasma cholesterol in humans. In addition, taurine chloramine, an endogenous product derived from activated neutrophils, has been reported to suppress obesity-induced oxidative stress and inflammation in adipocytes. Synthetic activity and concentration of taurine in adipose tissues and plasma have been shown to decrease in humans and animals during the development of obesity, suggesting a relationship between taurine deficiency and obesity. In this review, I summarize the effects of taurine on the progression of obesity in animal models and humans. Furthermore, I discuss possible mechanisms underlying the antiobesity effects of taurine. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. The Gut Microbiome, Obesity, and Weight Control in Women's Reproductive Health.

    Science.gov (United States)

    Greathouse, K Leigh; Faucher, Mary Ann; Hastings-Tolsma, Marie

    2017-08-01

    The microbes residing in the human gut, referred to as the microbiome, are intricately linked to energy homeostasis and subsequently obesity. Integral to the origins of obesity, the microbiome is believed to affect not only health of the human gut but also overall health. This microbiome-obesity association is mediated through the process of energy extraction, metabolism, and cross talk between the brain and the gut microbiome. Host exposures, including diet, that potentially modify genetic predisposition to obesity and affect weight management are reviewed. The higher prevalence of obesity among women and recent evidence linking obesity during pregnancy with offspring health make this topic particularly relevant. Current limitations in microbiome research to address obesity and future advances in this field are described. Applications of this science with respect to applied nursing and overall health care in general are included, with emphasis on the reproductive health of women and their offspring.

  6. Long-term characterization of the diet-induced obese and diet-resistant rat model

    DEFF Research Database (Denmark)

    Madsen, Andreas Nygaard; Hansen, Gitte; Paulsen, Sarah Juel

    2010-01-01

    The availability of useful animal models reflecting the human obesity syndrome is crucial in the search for novel compounds for the pharmacological treatment of obesity. In the current study, we have performed an extensive characterization of the obesity syndrome in a polygenetic animal model......, namely the selectively bred diet-induced obese (DIO) and diet-resistant (DR) rat strains. We show that they constitute useful models of the human obesity syndrome. DIO and DR rats were fed either a high-energy (HE) or a standard chow (Chow) diet from weaning to 9 months of age. Metabolic characterization...... including blood biochemistry and glucose homeostasis was examined at 2, 3, 6, and 9 months of age. Furthermore, in 6-month-old HE-fed DIO rats, the anti-obesity effects of liraglutide and sibutramine were examined in a 28-day study. Only HE-fed DIO rats developed visceral obesity, hyperleptinemia...

  7. Pediatric obesity: Current concepts.

    Science.gov (United States)

    Greydanus, Donald E; Agana, Marisha; Kamboj, Manmohan K; Shebrain, Saad; Soares, Neelkamal; Eke, Ransome; Patel, Dilip R

    2018-04-01

    This discussion reflects on concepts of obesity in children and adolescents in the early 21st century. It includes reflections on its history, definition, epidemiology, diagnostic perspectives, psychosocial considerations, musculoskeletal complications, endocrine complications and principles of management. In addition to emphasis on diet and exercise, research and clinical applications in the second decade of the 21 st century emphasize the increasing use of pharmacotherapy and bariatric surgery for adolescent and adult populations with critical problems of overweight and obesity. We conclude with a discussion of future directions in pediatric obesity management. Copyright © 2018 Mosby, Inc. All rights reserved.

  8. Psoriasis and Obesity

    DEFF Research Database (Denmark)

    Jensen, Peter; Skov, Lone

    2017-01-01

    Psoriasis is a common chronic inflammatory skin disease with a complex pathogenesis consisting of a genetic component, immune dysfunction, and environmental factors. It is associated with numerous comorbidities including psoriatic arthritis, cardiovascular disease, metabolic syndrome, and obesity....... Evidence suggests that obesity is a risk factor for incident psoriasis, aggravates existing psoriasis, and that weight reduction may improve the severity of psoriasis in overweight individuals. Excess body weight may interfere with the medical treatment used in psoriasis and adds to the cardiovascular risk...... profile in these patients, which underscores the importance of effective weight control regimens. In this review we examine the current literature with regard to the association between obesity and psoriasis....

  9. Obesity and Associated Comorbidities in People and Companion Animals: A One Health Perspective.

    Science.gov (United States)

    Chandler, M; Cunningham, S; Lund, E M; Khanna, C; Naramore, R; Patel, A; Day, M J

    2017-05-01

    This article reviews the biology, prevalence and risks for obesity in people and companion dogs and cats, and explores the links between obesity and diabetes mellitus and cancer across these species. Obesity is a major healthcare problem in both human and veterinary medicine and there is an increasing prevalence of obesity in people and pets. In people and animals, obesity is a complex disorder involving diet, level of physical activity, behavioural factors, socioeconomic factors, environment exposures, genetics, metabolism and the microbiome. Pets and people share a number of obesity-related comorbidities. Obesity is a major risk factor for type 2 diabetes mellitus in people and in cats, but this association is not recognized in dogs. Obesity is a recognized risk factor for a number of human cancers, but there are fewer data available describing this association with canine neoplastic disease. One approach to addressing the problem of obesity is by taking a 'One Health' perspective. Comparative clinical research examining shared lifestyle and environmental risk factors and the reasons underlying species differences should provide new perspectives on the fundamental biology of obesity. One Health programmes involving human healthcare professionals and veterinarians could help address obesity with simple interventions at the community level. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  10. Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes.

    Science.gov (United States)

    Carpenter, Danielle; Dhar, Sugandha; Mitchell, Laura M; Fu, Beiyuan; Tyson, Jess; Shwan, Nzar A A; Yang, Fengtang; Thomas, Mark G; Armour, John A L

    2015-06-15

    The human salivary amylase genes display extensive copy number variation (CNV), and recent work has implicated this variation in adaptation to starch-rich diets, and in association with body mass index. In this work, we use paralogue ratio tests, microsatellite analysis, read depth and fibre-FISH to demonstrate that human amylase CNV is not a smooth continuum, but is instead partitioned into distinct haplotype classes. There is a fundamental structural distinction between haplotypes containing odd or even numbers of AMY1 gene units, in turn coupled to CNV in pancreatic amylase genes AMY2A and AMY2B. Most haplotypes have one copy each of AMY2A and AMY2B and contain an odd number of copies of AMY1; consequently, most individuals have an even total number of AMY1. In contrast, haplotypes carrying an even number of AMY1 genes have rearrangements leading to CNVs of AMY2A/AMY2B. Read-depth and experimental data show that different populations harbour different proportions of these basic haplotype classes. In Europeans, the copy numbers of AMY1 and AMY2A are correlated, so that phenotypic associations caused by variation in pancreatic amylase copy number could be detected indirectly as weak association with AMY1 copy number. We show that the quantitative polymerase chain reaction (qPCR) assay previously applied to the high-throughput measurement of AMY1 copy number is less accurate than the measures we use and that qPCR data in other studies have been further compromised by systematic miscalibration. Our results uncover new patterns in human amylase variation and imply a potential role for AMY2 CNV in functional associations. © The Author 2015. Published by Oxford University Press.

  11. Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes

    Science.gov (United States)

    Carpenter, Danielle; Dhar, Sugandha; Mitchell, Laura M.; Fu, Beiyuan; Tyson, Jess; Shwan, Nzar A.A.; Yang, Fengtang; Thomas, Mark G.; Armour, John A.L.

    2015-01-01

    The human salivary amylase genes display extensive copy number variation (CNV), and recent work has implicated this variation in adaptation to starch-rich diets, and in association with body mass index. In this work, we use paralogue ratio tests, microsatellite analysis, read depth and fibre-FISH to demonstrate that human amylase CNV is not a smooth continuum, but is instead partitioned into distinct haplotype classes. There is a fundamental structural distinction between haplotypes containing odd or even numbers of AMY1 gene units, in turn coupled to CNV in pancreatic amylase genes AMY2A and AMY2B. Most haplotypes have one copy each of AMY2A and AMY2B and contain an odd number of copies of AMY1; consequently, most individuals have an even total number of AMY1. In contrast, haplotypes carrying an even number of AMY1 genes have rearrangements leading to CNVs of AMY2A/AMY2B. Read-depth and experimental data show that different populations harbour different proportions of these basic haplotype classes. In Europeans, the copy numbers of AMY1 and AMY2A are correlated, so that phenotypic associations caused by variation in pancreatic amylase copy number could be detected indirectly as weak association with AMY1 copy number. We show that the quantitative polymerase chain reaction (qPCR) assay previously applied to the high-throughput measurement of AMY1 copy number is less accurate than the measures we use and that qPCR data in other studies have been further compromised by systematic miscalibration. Our results uncover new patterns in human amylase variation and imply a potential role for AMY2 CNV in functional associations. PMID:25788522

  12. Brown adipose tissue in morbidly obese subjects.

    Directory of Open Access Journals (Sweden)

    Guy H E J Vijgen

    Full Text Available BACKGROUND: Cold-stimulated adaptive thermogenesis in brown adipose tissue (BAT to increase energy expenditure is suggested as a possible therapeutic target for the treatment of obesity. We have recently shown high prevalence of BAT in adult humans, which was inversely related to body mass index (BMI and body fat percentage (BF%, suggesting that obesity is associated with lower BAT activity. Here, we examined BAT activity in morbidly obese subjects and its role in cold-induced thermogenesis (CIT after applying a personalized cooling protocol. We hypothesize that morbidly obese subjects show reduced BAT activity upon cold exposure. METHODS AND FINDINGS: After applying a personalized cooling protocol for maximal non-shivering conditions, BAT activity was determined using positron-emission tomography and computed tomography (PET-CT. Cold-induced BAT activity was detected in three out of 15 morbidly obese subjects. Combined with results from lean to morbidly obese subjects (n = 39 from previous study, the collective data show a highly significant correlation between BAT activity and body composition (P<0.001, respectively explaining 64% and 60% of the variance in BMI (r = 0.8; P<0.001 and BF% (r = 0.75; P<0.001. Obese individuals demonstrate a blunted CIT combined with low BAT activity. Only in BAT-positive subjects (n = 26 mean energy expenditure was increased significantly upon cold exposure (51.5±6.7 J/s versus 44.0±5.1 J/s, P = 0.001, and the increase was significantly higher compared to BAT-negative subjects (+15.5±8.9% versus +3.6±8.9%, P = 0.001, indicating a role for BAT in CIT in humans. CONCLUSIONS: This study shows that in an extremely large range of body compositions, BAT activity is highly correlated with BMI and BF%. BAT-positive subjects showed higher CIT, indicating that BAT is also in humans involved in adaptive thermogenesis. Increasing BAT activity could be a therapeutic target in (morbid obesity.

  13. [Endocrine disruptors and obesity: obesogens].

    Science.gov (United States)

    García-Mayor, Ricardo V; Larrañaga Vidal, Alejandra; Docet Caamaño, Maria F; Lafuente Giménez, Anunciación

    2012-04-01

    Incidence and prevalence of owerweight and obesity have greatly increased over the past three decades in almost all countries around the world. This phenomenon is not easily explained by lifestyle changes in populations with very different initial habits. This has led to consider the influence of other factors, the so-called endocrine disruptors, and more specifically obesogens. This study reviewed the available evidence about polluting chemical substances which may potentially be obesogens in humans: DES, genistein, bisphenol A, organotins (TBT, TPT), and phthalates. The first three groups of substances mainly act upon estrogen receptors, while organotins and phthalates activate PPARγ. It was concluded that evidence exists of the obesogenic effect of these chemical substances in tissues and experimental animals, but few data are available in humans. Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.

  14. Greenhouse gas benefits of fighting obesity

    Energy Technology Data Exchange (ETDEWEB)

    Michaelowa, Axel [University of Zuerich, Muehlegasse 21, 8001 Zuerich (Switzerland); Dransfeld, Bjoern [Perspectives GmbH, Sonnenredder 55, 22045 Hamburg (Germany)

    2008-06-15

    Obesity has become a serious public health problem in both industrialized and rapidly industrializing countries. It increases greenhouse gas emissions through higher fuel needs for transportation of heavier people, lifecycle emissions from additional food production and methane emissions from higher amounts of organic waste. A reduction of average weight by 5 kg could reduce OECD transport CO{sub 2} emissions by more than 10 million t. While the shift from beef to other forms of meat in industrialized and countries in transition has lead to lifecycle emissions savings of 20 million t CO{sub 2} equivalent between 1990 and 2005, emissions due to obesity-promoting foodstuffs have increased by more than 400 million t in advanced developing countries. Emissions in OECD countries could be reduced by more than 4 million t through reduction of associated food waste. Due to the intimate behavioural nature of the obesity problem, policies to reduce obesity such as food taxation, subsidization of human-powered transport, incentives to reduce sedentary leisure and regulation of fat in foodstuffs have not yet been implemented to any extent. The emissions benefits of fiscal and regulatory measures to reduce obesity could accelerate the tipping point where a majority of voters feels that the problem warrants policy action. (author)

  15. Greenhouse gas benefits of fighting obesity

    International Nuclear Information System (INIS)

    Michaelowa, Axel; Dransfeld, Bjoern

    2008-01-01

    Obesity has become a serious public health problem in both industrialized and rapidly industrializing countries. It increases greenhouse gas emissions through higher fuel needs for transportation of heavier people, lifecycle emissions from additional food production and methane emissions from higher amounts of organic waste. A reduction of average weight by 5 kg could reduce OECD transport CO 2 emissions by more than 10 million t. While the shift from beef to other forms of meat in industrialized and countries in transition has lead to lifecycle emissions savings of 20 million t CO 2 equivalent between 1990 and 2005, emissions due to obesity-promoting foodstuffs have increased by more than 400 million t in advanced developing countries. Emissions in OECD countries could be reduced by more than 4 million t through reduction of associated food waste. Due to the intimate behavioural nature of the obesity problem, policies to reduce obesity such as food taxation, subsidization of human-powered transport, incentives to reduce sedentary leisure and regulation of fat in foodstuffs have not yet been implemented to any extent. The emissions benefits of fiscal and regulatory measures to reduce obesity could accelerate the tipping point where a majority of voters feels that the problem warrants policy action. (author)

  16. Childhood obesity: causes and consequences

    OpenAIRE

    Sahoo, Krushnapriya; Sahoo, Bishnupriya; Choudhury, Ashok Kumar; Sofi, Nighat Yasin; Kumar, Raman; Bhadoria, Ajeet Singh

    2015-01-01

    Childhood obesity has reached epidemic levels in developed as well as in developing countries. Overweight and obesity in childhood are known to have significant impact on both physical and psychological health. Overweight and obese children are likely to stay obese into adulthood and more likely to develop non-communicable diseases like diabetes and cardiovascular diseases at a younger age. The mechanism of obesity development is not fully understood and it is believed to be a disorder with m...

  17. The Psychological problems of Obesity

    OpenAIRE

    Mašková, Eva

    2013-01-01

    The aim of this thesis is to summarize findings of causes and consequences of obesity, the most common health problem in the world. The theoretical part deals with many key issues of obesity, from definition through the epidemiology, etiology and obesity prevention and treatment. However the main topics of this thesis are the psychological characteristics that are associated with obesity. It includes personality factors of obese people, willpower and self-control and specific psychopathology....

  18. Persistent Organic Pollutants as Risk Factors for Obesity and Diabetes.

    Science.gov (United States)

    Yang, Chunxue; Kong, Alice Pik Shan; Cai, Zongwei; Chung, Arthur C K

    2017-11-02

    The rising prevalence of obesity and diabetes cannot be fully explained by known risk factors, such as unhealthy diet, a sedentary lifestyle, and family history. This review summarizes the available studies linking persistent organic pollutants (POPs) to obesity and diabetes and discusses plausible underlying mechanisms. Increasing evidence suggest that POPs may act as obesogens and diabetogens to promote the development of obesity and diabetes and induce metabolic dysfunction. POPs are synthesized chemicals and are used widely in our daily life. These chemicals are resistant to degradation in chemical or biological processes, which enable them to exist in the environment persistently and to be bio-accumulated in animal and human tissue through the food chain. Increasingly, epidemiologic studies suggest a positive association between POPs and risk of developing diabetes. Understanding the relationship of POPs with obesity and diabetes may shed light on preventive strategies for obesity and diabetes.

  19. Does Inflammation Mediate the Association Between Obesity and Insulin Resistance?

    Science.gov (United States)

    Adabimohazab, Razieh; Garfinkel, Amanda; Milam, Emily C; Frosch, Olivia; Mangone, Alexander; Convit, Antonio

    2016-06-01

    In adult obesity, low-grade systemic inflammation is considered an important step in the pathogenesis of insulin resistance (IR). The association between obesity and inflammation is less well established in adolescents. Here, we ascertain the importance of inflammation in IR among obese adolescents by utilizing either random forest (RF) classification or mediation analysis approaches. The inflammation balance score, composed of eight pro- and anti-inflammatory makers, as well as most of the individual inflammatory markers differed significantly between lean and overweight/obese. In contrast, adiponectin was the only individual marker selected as a predictor of IR by RF, and the balance score only revealed a medium-to-low importance score. Neither adiponectin nor the inflammation balance score was found to mediate the relationship between obesity and IR. These findings do not support the premise that low-grade systemic inflammation is a key for the expression of IR in the human. Prospective longitudinal studies should confirm these findings.

  20. Obesity: modern man's fertility nemesis.

    Science.gov (United States)

    Cabler, Stephanie; Agarwal, Ashok; Flint, Margot; du Plessis, Stefan S

    2010-07-01

    The obesity pandemic has grown to concerning proportions in recent years, not only in the Western World, but in developing countries as well. The corresponding decrease in male fertility and fecundity may be explained in parallel to obesity, and obesity should be considered as an etiology of male fertility. Studies show that obesity contributes to infertility by reducing semen quality, changing sperm proteomes, contributing to erectile dysfunction, and inducing other physical problems related to obesity. Mechanisms for explaining the effect of obesity on male infertility include abnormal reproductive hormone levels, an increased release of adipose-derived hormones and adipokines associated with obesity, and other physical problems including sleep apnea and increased scrotal temperatures. Recently, genetic factors and markers for an obesity-related infertility have been discovered and may explain the difference between fertile obese and infertile obese men. Treatments are available for not only infertility related to obesity, but also as a treatment for the other comorbidities arising from obesity. Natural weight loss, as well as bariatric surgery are options for obese patients and have shown promising results in restoring fertility and normal hormonal profiles. Therapeutic interventions including aromatase inhibitors, exogenous testosterone replacement therapy and maintenance and regulation of adipose-derived hormones, particularly leptin, may also be able to restore fertility in obese males. Because of the relative unawareness and lack of research in this area, controlled studies should be undertaken and more focus should be given to obesity as an etiolgy of male infertility.

  1. Mutational analysis of the UCP2 core promoter and relationships of variants with obesity

    DEFF Research Database (Denmark)

    Dalgaard, Louise T; Andersen, Gitte; Larsen, Lesli H

    2003-01-01

    To identify polymorphisms in the human uncoupling protein 2 gene (UCP2) promoter and to investigate whether these were associated with obesity or weight gain.......To identify polymorphisms in the human uncoupling protein 2 gene (UCP2) promoter and to investigate whether these were associated with obesity or weight gain....

  2. Homeostatic theory of obesity

    Directory of Open Access Journals (Sweden)

    David F Marks

    2015-06-01

    Full Text Available Health is regulated by homeostasis, a property of all living things. Homeostasis maintains equilibrium at set-points using feedback loops for optimum functioning of the organism. Imbalances in homeostasis causing overweight and obesity are evident in more than 1 billion people. In a new theory, homeostatic obesity imbalance is attributed to a hypothesized ‘Circle of Discontent’, a system of feedback loops linking weight gain, body dissatisfaction, negative affect and over-consumption. The Circle of Discontent theory is consistent with an extensive evidence base. A four-armed strategy to halt the obesity epidemic consists of (1 putting a stop to victim-blaming, stigma and discrimination; (2 devalorizing the thin-ideal; (3 reducing consumption of energy-dense, low-nutrient foods and drinks; and (4 improving access to plant-based diets. If fully implemented, interventions designed to restore homeostasis have the potential to halt the obesity epidemic.

  3. Homeostatic theory of obesity.

    Science.gov (United States)

    Marks, David F

    2015-01-01

    Health is regulated by homeostasis, a property of all living things. Homeostasis maintains equilibrium at set-points using feedback loops for optimum functioning of the organism. Imbalances in homeostasis causing overweight and obesity are evident in more than 1 billion people. In a new theory, homeostatic obesity imbalance is attributed to a hypothesized 'Circle of Discontent', a system of feedback loops linking weight gain, body dissatisfaction, negative affect and over-consumption. The Circle of Discontent theory is consistent with an extensive evidence base. A four-armed strategy to halt the obesity epidemic consists of (1) putting a stop to victim-blaming, stigma and discrimination; (2) devalorizing the thin-ideal; (3) reducing consumption of energy-dense, low-nutrient foods and drinks; and (4) improving access to plant-based diets. If fully implemented, interventions designed to restore homeostasis have the potential to halt the obesity epidemic.

  4. The obese pregnancy.

    Science.gov (United States)

    Aamir, A H

    2016-09-01

    Weight gain in pregnancy is physiological but if a woman is overweight prior to pregnancy, this will put both women and foetus at risk of adverse complications. Obesity can affect women at all the stages of pregnancy. Obese women can be a cause of reduced fertility as compared to a normal weight woman, and a typical example is of the Polycystic ovarian syndrome (PCOS). The incidence of Gestational Diabetes Mellitus ,hypertension and preeclamsia is 2-3 folds higher in obesity particularly with a BMI of> 30kg/m2. The chances of thromboembolism, miscarriage, Caesarian - section and stillbirth are increased as well. Perinatal mortality, increased chances of genetic disorders of the foetus and macrosomia are all increased with obesity. To avoid all these complications health education regarding healthy life style and diet with regular moderate intensity exercise is the cornerstone of the management.

  5. Obesity and asthma

    Directory of Open Access Journals (Sweden)

    Pranab Baruwa

    2013-01-01

    Full Text Available Asthma is a chronic disorder affecting millions of people worldwide. The prevalence of asthma is around 300 million and is expected to increase another 100 million by 2025. Obesity, on the other hand, also affects a large number of individuals. Overweight in adults is defined when body mass index (BMI is between 25 to 30 kg/m 2 and obesity when the BMI >30 kg/m 2 . It has been a matter of interest for researchers to find a relation between these two conditions. This knowledge will provide a new insight into the management of both conditions. At present, obese asthma patients may be considered a special category and it is important to assess the impact of management of obesity on asthma symptoms.

  6. Reducing Childhood Obesity

    Science.gov (United States)

    ... 90-minute instructional sessions. We Can! is unique among existing youth obesity-prevention initiatives because it focuses its activities and education on parents and caregivers—the primary group influencing children and adolescents. Joining in this effort with the ...

  7. Obesity and African Americans

    Science.gov (United States)

    ... nchs/nhis/shs/tables.htm CHILDREN Percentage of obesity among children and adolescents 6–11 years of age, 2011- ... ADOLESCENTS Percentage of high school students who were overweight, 2015 Black White Black / White Ratio Girls 21. ...

  8. Obesity in Children

    Science.gov (United States)

    ... much body fat. It is different from being overweight, which means weighing too much. Both terms mean ... know when a child has obesity or is overweight. Ask your health care provider to check whether ...

  9. Obesity and Hispanic Americans

    Science.gov (United States)

    ... hus16.pdf [PDF | 11.14MB] CHILDREN Percentage of obesity among children and adolescents 6-11 years of age, 2011- ... ADOLESCENTS Percentage of high school students who were overweight, 2015 Hispanic White Hispanic / White Ratio Girls 20. ...

  10. Health risks of obesity

    Science.gov (United States)

    ... heart disease and type 2 diabetes. People with "apple-shaped" bodies (waist is bigger than the hips) ... Obesity Browse the Encyclopedia A.D.A.M., Inc. is accredited by URAC, also known as the ...

  11. Homeostatic theory of obesity

    Science.gov (United States)

    2015-01-01

    Health is regulated by homeostasis, a property of all living things. Homeostasis maintains equilibrium at set-points using feedback loops for optimum functioning of the organism. Imbalances in homeostasis causing overweight and obesity are evident in more than 1 billion people. In a new theory, homeostatic obesity imbalance is attributed to a hypothesized ‘Circle of Discontent’, a system of feedback loops linking weight gain, body dissatisfaction, negative affect and over-consumption. The Circle of Discontent theory is consistent with an extensive evidence base. A four-armed strategy to halt the obesity epidemic consists of (1) putting a stop to victim-blaming, stigma and discrimination; (2) devalorizing the thin-ideal; (3) reducing consumption of energy-dense, low-nutrient foods and drinks; and (4) improving access to plant-based diets. If fully implemented, interventions designed to restore homeostasis have the potential to halt the obesity epidemic. PMID:28070357

  12. Childhood Obesity Causes & Consequences

    Science.gov (United States)

    ... 2013;62(15):1309–1319. Lloyd LJ, Langley-Evans SC, McMullen S. Childhood obesity and risk of the ... et al. Association of depression and health related quality of life with body composition in children and ...

  13. Pharmacological treatment of obesity.

    Science.gov (United States)

    Mancini, Marcio C; Halpern, Alfredo

    2006-04-01

    This review offers an overview of physiological agents, current therapeutics, as well as medications, which have been extensively used and those agents not currently available or non-classically considered anti-obesity drugs. As obesity - particularly that of central distribution - represents an important triggering factor for insulin resistance, its pharmacological treatment is relevant in the context of metabolic syndrome control. The authors present an extensive review on the criteria for anti-obesity management efficacy, on physiological mechanisms that regulate central and/or peripheral energy homeostasis (nutrients, monoamines, and peptides), on beta-phenethylamine pharmacological derivative agents (fenfluramine, dexfenfluramine, phentermine and sibutramine), tricyclic derivatives (mazindol), phenylpropanolamine derivatives (ephedrin, phenylpropanolamine), phenylpropanolamine oxytrifluorphenyl derivative (fluoxetine), a naftilamine derivative (sertraline) and a lipstatine derivative (orlistat). An analysis of all clinical trials - over ten-week long - is also presented for medications used in the management of obesity, as well as data about future medications, such as a the inverse cannabinoid agonist, rimonabant.

  14. Sexual function and obesity

    DEFF Research Database (Denmark)

    Larsen, S H; Wagner, G; Heitmann, B L

    2007-01-01

    function and dysfunction. COMMENTS: Four prospective and seven cross-sectional studies were found describing association between obesity and erectile dysfunction (ED). One cross-sectional study was found describing obesity and female sexual dysfunction (FSD). The prospective studies on ED all demonstrated......OBJECTIVE: To review the literature on the relationship between obesity and sexual function. METHOD: A search in the medical literature from 1966 and onwards was carried out through Medline and Embase for publications on obesity, in combination with Medical Subject Heading words related to sexual...... a direct association and so did five of the seven cross-sectional studies. The single FSD study did not find any relationship. Eight intervention studies on weight loss and sexual difficulties were identified. All included few individuals and results were mixed even if most indicated an increase of sexual...

  15. Obesity and Asian Americans

    Science.gov (United States)

    ... 5 12.4 0.4 Source: High School Youth Risk Behavior Survey Data. Available at http://nccd.cdc.gov/youthonline . [Accessed 08/18/2017] HEALTH IMPACT OF OBESITY People who are overweight are more likely to ...

  16. Childhood Obesity PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2013-08-06

    This 60 second public service announcement is based on the August 2013 CDC Vital Signs report. The rate of obesity among low-income preschoolers has declined, but one in eight is still obese. This program briefly discusses what can be done.  Created: 8/6/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 8/6/2013.

  17. Cultivating childhood obesity

    OpenAIRE

    Greene-Martin, DeCleasha

    2013-01-01

    In recent years the levels of obesity in the United States has risen greatly especially amongst children. Doctors, psychologists, and other scientists have been studying the growing problem for years. Implications for childhood obesity not only have enormous physical consequences but emotional repercussions which can affect the child’s academic and social development. A number of factors have been identified as having an effect on these children; family life reveals the grocery store habits o...

  18. Obesity and Women

    Centers for Disease Control (CDC) Podcasts

    2009-05-11

    This women's health podcast focuses on obesity in women and girls. It discusses obesity-related health risks and includes tips to help achieve and maintain a healthy weight.  Created: 5/11/2009 by Office of Women’s Health (OWH) and National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 5/11/2009.

  19. Maternal obesity and preeclampsia

    OpenAIRE

    Azar Aghamohammadi

    2011-01-01

    Background: Obesity is a modern day epidemic. The incidence appears to be rapidly increasing in bothdeveloped and developing countries and has become much more obvious in the last decade.Aim& Objective: The present research was done with the aim of studying the effects of obesity definedas a first trimester maternal body mass index >30 on the preeclampsia.Methods: This study was a descriptive-comparative study two hundred fifty singleton pregnancies ofwomen with first trimester BMI >30 who de...

  20. Starches, Sugars and Obesity

    OpenAIRE

    Aller, Erik E. J. G.; Abete, Itziar; Astrup, Arne; Martinez, J. Alfredo; van Baak, Marleen A.

    2011-01-01

    The rising prevalence of obesity, not only in adults but also in children and adolescents, is one of the most important public health problems in developed and developing countries. As one possible way to tackle obesity, a great interest has been stimulated in understanding the relationship between different types of dietary carbohydrate and appetite regulation, body weight and body composition. The present article reviews the conclusions from recent reviews and meta-analyses on the effects o...