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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. Splanchnic lipolysis in human obesity

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    Nielsen, Soren; Guo, ZengKui; Johnson, C. Michael; Hensrud, Donald D.; Jensen, Michael D.

    2004-01-01

    Elevated FFA concentrations have been shown to reproduce some of the metabolic abnormalities of obesity. It has been hypothesized that visceral adipose tissue lipolysis releases excess FFAs into the portal vein, exposing the liver to higher FFA concentrations. We used isotope dilution/hepatic vein catheterization techniques to examine whether intra-abdominal fat contributes a greater portion of hepatic FFA delivery in visceral obesity. Obese women (n = 24) and men (n = 20) with a range of obesity phenotypes, taken together with healthy, lean women (n = 12) and men (n = 12), were studied. Systemic, splanchnic, and leg FFA kinetics were measured. The results showed that plasma FFA concentrations were approximately 20% greater in obese men and obese women. The contribution of splanchnic lipolysis to hepatic FFA delivery ranged from less than 10% to almost 50% and increased as a function of visceral fat in women (r = 0.49, P = 0.002) and in men (r = 0.52, P = 0.002); the slope of the relationship was greater in women than in men (P < 0.05). Leg and splanchnic tissues contributed a greater portion of systemic FFA release in obese men and women than in lean men and women. We conclude that the contribution of visceral adipose tissue lipolysis to hepatic FFA delivery increases with increasing visceral fat in humans and that this effect is greater in women than in men. PMID:15173884

  3. Genetic aspects of human obesity.

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    Larder, Rachel; Lim, Chung Thong; Coll, Anthony P

    2014-01-01

    Obesity and its related metabolic consequences represent a major public health problem. Huge changes within the environment have undoubtedly contributed to the increased prevalence of obesity but genetic factors are also critical in determining an individual's predisposition to gain weight. The last two decades have seen a huge increase in the understanding of the mechanisms controlling appetitive behavior, body composition, and energy expenditure. Many regions throughout the central nervous system play critical roles in these processes but the hypothalamus, in particular, receives and orchestrates a variety of signals to bring about coordinated changes in energy balance. Reviewing data from human genetic and model organism studies, we consider how disruptions of hypothalamic pathways evolved to maintain energy homeostasis and go on to cause obesity. We highlight ongoing technological developments which continue to lead to novel insights and discuss how this increased knowledge may lead to effective therapeutic interventions in the future.

  4. Splanchnic lipolysis in human obesity

    OpenAIRE

    Nielsen, Soren; Guo, ZengKui; Johnson, C. Michael; Hensrud, Donald D.; Jensen, Michael D

    2004-01-01

    Elevated FFA concentrations have been shown to reproduce some of the metabolic abnormalities of obesity. It has been hypothesized that visceral adipose tissue lipolysis releases excess FFAs into the portal vein, exposing the liver to higher FFA concentrations. We used isotope dilution/hepatic vein catheterization techniques to examine whether intra-abdominal fat contributes a greater portion of hepatic FFA delivery in visceral obesity. Obese women (n = 24) and men (n = 20) with a range of obe...

  5. Genetic & epigenetic approach to human obesity

    Directory of Open Access Journals (Sweden)

    K Rajender Rao

    2014-01-01

    Full Text Available Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D, cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12 th u0 pdate of Human Obesity Gene Map there are 253 quantity trait loci (QTL for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed.

  6. Genetic & epigenetic approach to human obesity.

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    Rao, K Rajender; Lal, Nirupama; Giridharan, N V

    2014-11-01

    Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D), cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS) have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12th Update of Human Obesity Gene Map there are 253 quantity trait loci (QTL) for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed.

  7. Obesity changes the human gut mycobiome.

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    Mar Rodríguez, M; Pérez, Daniel; Javier Chaves, Felipe; Esteve, Eduardo; Marin-Garcia, Pablo; Xifra, Gemma; Vendrell, Joan; Jové, Mariona; Pamplona, Reinald; Ricart, Wifredo; Portero-Otin, Manuel; Chacón, Matilde R; Fernández Real, José Manuel

    2015-10-12

    The human intestine is home to a diverse range of bacterial and fungal species, forming an ecological community that contributes to normal physiology and disease susceptibility. Here, the fungal microbiota (mycobiome) in obese and non-obese subjects was characterized using Internal Transcribed Spacer (ITS)-based sequencing. The results demonstrate that obese patients could be discriminated by their specific fungal composition, which also distinguished metabolically "healthy" from "unhealthy" obesity. Clusters according to genus abundance co-segregated with body fatness, fasting triglycerides and HDL-cholesterol. A preliminary link to metabolites such as hexadecanedioic acid, caproic acid and N-acetyl-L-glutamic acid was also found. Mucor racemosus and M. fuscus were the species more represented in non-obese subjects compared to obese counterparts. Interestingly, the decreased relative abundance of the Mucor genus in obese subjects was reversible upon weight loss. Collectively, these findings suggest that manipulation of gut mycobiome communities might be a novel target in the treatment of obesity.

  8. Obesity accelerates epigenetic aging of human liver

    OpenAIRE

    Horvath, S; Erhart, W.; Brosch, M; Ammerpohl, O.; von Schonfels, W.; Ahrens, M.; Heits, N.; Bell, J.T.; Tsai, P.-C.; Spector, T D; Deloukas, P.; Siebert, R.; Sipos, B.; Becker, T.; Rocken, C.

    2014-01-01

    Because obese people are at an increased risk of many age-related diseases, it is a plausible hypothesis that obesity increases the biological age of some tissues and cell types. However, it has been difficult to detect such an accelerated aging effect because it is unclear how to measure tissue age. Here we use a recently developed biomarker of aging (known as “epigenetic clock”) to study the relationship between epigenetic age and obesity in several human tissues. We report an unexpectedly ...

  9. The genetics of human obesity.

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    Waalen, Jill

    2014-10-01

    The heritability of obesity has long been appreciated and the genetics of obesity has been the focus of intensive study for decades. Early studies elucidating genetic factors involved in rare monogenic and syndromic forms of extreme obesity focused attention on dysfunction of hypothalamic leptin-related pathways in the control of food intake as a major contributor. Subsequent genome-wide association studies of common genetic variants identified novel loci that are involved in more common forms of obesity across populations of diverse ethnicities and ages. The subsequent search for factors contributing to the heritability of obesity not explained by these 2 approaches ("missing heritability") has revealed additional rare variants, copy number variants, and epigenetic changes that contribute. Although clinical applications of these findings have been limited to date, the increasing understanding of the interplay of these genetic factors with environmental conditions, such as the increased availability of high calorie foods and decreased energy expenditure of sedentary lifestyles, promises to accelerate the translation of genetic findings into more successful preventive and therapeutic interventions.

  10. Sympathetic nervous system behavior in human obesity.

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    Davy, Kevin P; Orr, Jeb S

    2009-02-01

    The sympathetic nervous system (SNS) plays an essential role in the regulation of metabolic and cardiovascular homeostasis. Low SNS activity has been suggested to be a risk factor for weight gain and obesity development. In contrast, SNS activation is characteristic of a number of metabolic and cardiovascular diseases that occur more frequently in obese individuals. Until recently, the relation between obesity and SNS behavior has been controversial because previous approaches for assessing SNS activity in humans have produced inconsistent findings. Beginning in the early 1990s, many studies using state of the art neurochemical and neurophysiological techniques have provided important insight. The purpose of the present review is to provide an overview of our current understanding of the region specific alterations in SNS behavior in human obesity. We will discuss findings from our own laboratory which implicate visceral fat as an important depot linking obesity with skeletal muscle SNS activation. The influence of weight change on SNS behavior and the potential mechanisms and consequences of region specific SNS activation in obesity will also be considered.

  11. 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....

  12. Contribution of daily and seasonal biorhythms to obesity in humans

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    Kanikowska, Dominika; Sato, Maki; Witowski, Janusz

    2015-04-01

    While the significance of obesity as a serious health problem is well recognized, little is known about whether and how biometerological factors and biorhythms causally contribute to obesity. Obesity is often associated with altered seasonal and daily rhythmicity in food intake, metabolism and adipose tissue function. Environmental stimuli affect both seasonal and daily rhythms, and the latter are under additional control of internal molecular oscillators, or body clocks. Modifications of clock genes in animals and changes to normal daily rhythms in humans (as in shift work and sleep deprivation) result in metabolic dysregulation that favours weight gain. Here, we briefly review the potential links between biorhythms and obesity in humans.

  13. 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.

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

    DEFF Research Database (Denmark)

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

    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...... for identifying, describing, and discussing future potential in obesity research, to establish new and to nurture existing networks and collaborations between researchers across the social sciences and humanities and the natural sciences with an interest in obesity research, and thereby to mobilise significant...

  15. 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

    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...... 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...... of animals in obesity research as especially problematic....

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

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    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.

  17. 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.

  18. Genetic & epigenetic approach to human obesity

    OpenAIRE

    K Rajender Rao; Nirupama Lal; N V Giridharan

    2014-01-01

    Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D), cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advanceme...

  19. Activation of the peripheral endocannabinoid system in human obesity.

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    Engeli, Stefan; Böhnke, Jana; Feldpausch, Mareike; Gorzelniak, Kerstin; Janke, Jürgen; Bátkai, Sándor; Pacher, Pál; Harvey-White, Judy; Luft, Friedrich C; Sharma, Arya M; Jordan, Jens

    2005-10-01

    Obesity is the main risk factor for the development of type 2 diabetes. Activation of the central endocannabinoid system increases food intake and promotes weight gain. Blockade of the cannabinoid type 1 (CB-1) receptor reduces body weight in animals by central and peripheral actions; the role of the peripheral endocannabinoid system in human obesity is now being extensively investigated. We measured circulating endocannabinoid concentrations and studied the expression of CB-1 and the main degrading enzyme, fatty acid amide hydrolase (FAAH), in adipose tissue of lean (n = 20) and obese (n = 20) women and after a 5% weight loss in a second group of women (n = 17). Circulating levels of anandamide and 1/2-arachidonoylglycerol were increased by 35 and 52% in obese compared with lean women (P obese subjects (P endocannabinoids. Circulating endocannabinoids and CB-1 or FAAH expression were not affected by 5% weight loss. The expression of CB-1 and FAAH was increased in mature human adipocytes compared with in preadipocytes and was found in several human tissues. Our findings support the presence of a peripheral endocannabinoid system that is upregulated in human obesity.

  20. Microbial ecology: human gut microbes associated with obesity.

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    Ley, Ruth E; Turnbaugh, Peter J; Klein, Samuel; Gordon, Jeffrey I

    2006-12-21

    Two groups of beneficial bacteria are dominant in the human gut, the Bacteroidetes and the Firmicutes. Here we show that the relative proportion of Bacteroidetes is decreased in obese people by comparison with lean people, and that this proportion increases with weight loss on two types of low-calorie diet. Our findings indicate that obesity has a microbial component, which might have potential therapeutic implications.

  1. Metabolic thrift and the genetic basis of human obesity

    OpenAIRE

    O’Rourke, Robert W.

    2014-01-01

    Evolution has molded metabolic thrift within humans, a genetic heritage that, when thrust into our modern “obesogenic” environment, creates the current obesity crisis. Modern genetic analysis has identified genetic and epigenetic contributors to obesity, an understanding of which will guide the development of environmental, pharmacologic, and genetic therapeutic interventions. “The voyage was so long, food and water ran out. One hundred of the paddlers died; forty men remained. The voyager...

  2. Human gut microbiota in obesity and after gastric bypass.

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    Zhang, Husen; DiBaise, John K; Zuccolo, Andrea; Kudrna, Dave; Braidotti, Michele; Yu, Yeisoo; Parameswaran, Prathap; Crowell, Michael D; Wing, Rod; Rittmann, Bruce E; Krajmalnik-Brown, Rosa

    2009-02-17

    Recent evidence suggests that the microbial community in the human intestine may play an important role in the pathogenesis of obesity. We examined 184,094 sequences of microbial 16S rRNA genes from PCR amplicons by using the 454 pyrosequencing technology to compare the microbial community structures of 9 individuals, 3 in each of the categories of normal weight, morbidly obese, and post-gastric-bypass surgery. Phylogenetic analysis demonstrated that although the Bacteria in the human intestinal community were highly diverse, they fell mainly into 6 bacterial divisions that had distinct differences in the 3 study groups. Specifically, Firmicutes were dominant in normal-weight and obese individuals but significantly decreased in post-gastric-bypass individuals, who had a proportional increase of Gammaproteobacteria. Numbers of the H(2)-producing Prevotellaceae were highly enriched in the obese individuals. Unlike the highly diverse Bacteria, the Archaea comprised mainly members of the order Methanobacteriales, which are H(2)-oxidizing methanogens. Using real-time PCR, we detected significantly higher numbers of H(2)-utilizing methanogenic Archaea in obese individuals than in normal-weight or post-gastric-bypass individuals. The coexistence of H(2)-producing bacteria with relatively high numbers of H(2)-utilizing methanogenic Archaea in the gastrointestinal tract of obese individuals leads to the hypothesis that interspecies H(2) transfer between bacterial and archaeal species is an important mechanism for increasing energy uptake by the human large intestine in obese persons. The large bacterial population shift seen in the post-gastric-bypass individuals may reflect the double impact of the gut alteration caused by the surgical procedure and the consequent changes in food ingestion and digestion.

  3. The gut microbiota in human energy homeostasis and obesity.

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    Rosenbaum, Michael; Knight, Rob; Leibel, Rudolph L

    2015-09-01

    Numerous studies of rodents suggest that the gut microbiota populations are sensitive to genetic and environmental influences, and can produce or influence afferent signals that directly or indirectly impinge on energy homeostatic systems affecting both energy balance (weight gain or loss) and energy stores. Fecal transplants from obese and lean human, and from mouse donors to gnotobiotic mice, result in adoption of the donor somatotype by the formerly germ-free rodents. Thus, the microbiota is certainly implicated in the development of obesity, adiposity-related comorbidities, and the response to interventions designed to achieve sustained weight reduction in mice. More studies are needed to determine whether the microbiota plays a similarly potent role in human body-weight regulation and obesity.

  4. Altered autophagy in human adipose tissues in obesity

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    Context: Autophagy is a housekeeping mechanism, involved in metabolic regulation and stress response, shown recently to regulate lipid droplets biogenesis/breakdown and adipose tissue phenotype. Objective: We hypothesized that in human obesity autophagy may be altered in adipose tissue in a fat d...

  5. Laboratory animals as surrogate models of human obesity

    Institute of Scientific and Technical Information of China (English)

    Cecilia NILSSON; Kirsten RAUN; Fei-fei YAN; Marianne O LARSEN; Mads TANG-CHRISTENSEN

    2012-01-01

    Obesity and obesity-related metabolic diseases represent a growing socioeconomic problem throughout the world.Great emphasis has been put on establishing treatments for this condition,including pharmacological intervention.However,there are many obstacles and pitfalls in the development process from pre-clinical research to the pharmacy counter,and there is no certainty that what has been observed pre-clinically will translate into an improvement in human health.Hence,it is important to test potential new drugs in a valid translational model early in their development.In the current mini-review,a number of monogenetic and polygenic models of obesity will be discussed in view of their translational character.

  6. Obesity

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    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 occurs over time when you eat more calories ...

  7. Malnutritive obesity ('malnubesity'): is it driven by human brain evolution?

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    McGill, Anne-Thea

    2008-12-01

    Abstract Health messages on low-energy diets for healthy weight loss are muddled and not working, and obesity rates are rising. Are there missing links? Accumulating evidence shows that humans have well developed 'self-addictive' appetite pathways to enhance the uptake of highly energy-dense food. Humans synthesize fewer co-factors and vitamins than other mammals and must ingest them. Both processes probably arose to maximize available energy for the developing, large association cortex of the human brain. The default phenotype resulting from consuming an 'addictive', westernized, highly refined, energy-dense, hypomicronutrient diet is 'malnutritive obesity' or 'malnubesity'. A relative lack of antioxidant (and other) co-factors contributes to inefficiently oxidized energy. This 'stress' leads to central fat deposition, disordered energy use by cell mitochondria, especially in muscle and liver, and malfunctioning immune, coagulation, endothelial, and other systems. The resultant problems appear to range from epigenetic reprogramming in utero to end organ damage of the metabolic syndrome and the immune failure of cancer. Treatment of 'malnubesity' may require: (1) understanding the drivers and mechanisms of addictions, (2) reprioritizing satiating, micronutrient-dense whole foods, (3) nonjudgmental general, psychological, and medical support for those at risk or affected by obesity; and (4) practical incentives/regulation for healthy food production and distribution.

  8. 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.

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

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    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.

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

    Directory of Open Access Journals (Sweden)

    Isabelle Matias

    Full Text Available 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 (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

  11. 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

    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....... 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....... of hypertension. Due to this inconsistency, we decided to study adiponectin from two aspects in a cross-sectional in vivo study and in an experimental in vitro study. In the cross-sectional study, 103 men with body mass index (BMI) ≥ 30.0 kg/m(2) were studied; 63 had 24-hr ambulatory blood pressure (ABP) ≥ 130...

  12. SAA is Found on ApoB-Containing Lipoproteins in Obese Diabetic Humans

    OpenAIRE

    Jahangiri, Anisa; Wilson, Patricia G.; Hou, Tianfei; Brown, Aparna; King, Victoria L.; Tannock, Lisa R.

    2013-01-01

    In murine models of obesity/diabetes there is an increase in plasma SAA levels along with redistribution of SAA from high density lipoprotein (HDL) to apo-B containing lipoprotein particles, namely low density lipoprotein (LDL) and very low density lipoprotein (VLDL). The goal of this study was to determine if obesity is associated with similar SAA lipoprotein redistribution in humans. Three groups of obese individuals were recruited from a weight loss clinic: healthy obese (n=14), metabolic ...

  13. Human Carboxylesterase 2 Reverses Obesity-Induced Diacylglycerol Accumulation and Glucose Intolerance

    OpenAIRE

    Maxwell A. Ruby; Julie Massart; Hunerdosse, Devon M.; Milena Schönke; Jorge C. Correia; Louie, Sharon M.; Ruas, Jorge L.; Erik Näslund; Nomura, Daniel K.; Zierath, Juleen R.

    2017-01-01

    Serine hydrolases are a large family of multifunctional enzymes known to influence obesity. Here, we performed activity-based protein profiling to assess the functional level of serine hydrolases in liver biopsies from lean and obese humans in order to gain mechanistic insight into the pathophysiology of metabolic disease. We identified reduced hepatic activity of carboxylesterase 2 (CES2) and arylacetamide deacetylase (AADAC) in human obesity. In primary human hepatocytes, CES2 knockdown imp...

  14. 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

    Obesity is a heritable disorder, with children of obese fathers at higher risk of developing obesity. Environmental factors epigenetically influence somatic tissues, but the contribution of these factors to the establishment of epigenetic patterns in human gametes is unknown. Here, we hypothesized...... that weight loss remodels the epigenetic signature of spermatozoa in human obesity. Comprehensive profiling of the epigenome of sperm from lean and obese men showed similar histone positioning, but small non-coding RNA expression and DNA methylation patterns were markedly different. In a separate cohort...

  15. Human obesity: an evolutionary approach to understanding our bulging waistline.

    Science.gov (United States)

    Lev-Ran, A

    2001-01-01

    The unique worldwide spread of the human species and the remarkably long post-reproductive survival show that our genome permits excellent adaptation to vastly different environments. Moreover, the main scourges of later age, namely malignant growths and atherosclerosis, appear in humans later than in shorter-living animals. In recent years, excess weight and obesity have become mass phenomena with a pronounced upward trend in all developed countries. However, despite the detrimental effects of being overweight, these populations live longer than ever, which in part may be explained by the availability of better medical treatment. The prevalence and predicted further spread of obesity can be understood in the light of evolution. In all animal species energy metabolism is asymmetric with energy accumulation ('thrifty genotype') being the necessary condition of survival during hard times. For humans, which are no different to other animals in this respect, this genetic programming was necessary for survival because during the course of history, including the recorded history in the more developed Middle East, Europe or China, there was never a long period of uninterrupted food abundance, whereas famines were regular and frequent. Therefore fat accumulation, when food was available, meant survival at times of shortage, while the possible detrimental effects of overindulgence in food and being overweight expressed in unrealistically old age were irrelevant. It is the central, mostly intra-abdominal fat (in both humans and animals) that is more medically important than the subcutaneous truncal fat, and the accumulation of both types of fat is conditioned by high food consumption; therefore it is a historic novelty for human populations. In contrast, lower-body fat in human females is unique in the animal kingdom: it is much less metabolically active, it is of much lower pathologic significance than central fat, and it is programmed to be mobilized mostly during

  16. 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...

  17. Three-dimensional surface imaging system for assessing human obesity

    Science.gov (United States)

    Xu, Bugao; Yu, Wurong; Yao, Ming; Pepper, M. Reese; Freeland-Graves, Jeanne H.

    2009-10-01

    The increasing prevalence of obesity suggests a need to develop a convenient, reliable, and economical tool for assessment of this condition. Three-dimensional (3-D) body surface imaging has emerged as an exciting technology for the estimation of body composition. We present a new 3-D body imaging system, which is designed for enhanced portability, affordability, and functionality. In this system, stereo vision technology is used to satisfy the requirement for a simple hardware setup and fast image acquisition. The portability of the system is created via a two-stand configuration, and the accuracy of body volume measurements is improved by customizing stereo matching and surface reconstruction algorithms that target specific problems in 3-D body imaging. Body measurement functions dedicated to body composition assessment also are developed. The overall performance of the system is evaluated in human subjects by comparison to other conventional anthropometric methods, as well as air displacement plethysmography, for body fat assessment.

  18. A 3D surface imaging system for assessing human obesity

    Science.gov (United States)

    Xu, B.; Yu, W.; Yao, M.; Yao, X.; Li, Q.; Pepper, M. R.; Freeland-Graves, J. H.

    2009-08-01

    The increasing prevalence of obesity suggests a need to develop a convenient, reliable and economical tool for assessment of this condition. Three-dimensional (3D) body surface imaging has emerged as an exciting technology for estimation of body composition. This paper presents a new 3D body imaging system, which was designed for enhanced portability, affordability, and functionality. In this system, stereo vision technology was used to satisfy the requirements for a simple hardware setup and fast image acquisitions. The portability of the system was created via a two-stand configuration, and the accuracy of body volume measurements was improved by customizing stereo matching and surface reconstruction algorithms that target specific problems in 3D body imaging. Body measurement functions dedicated to body composition assessment also were developed. The overall performance of the system was evaluated in human subjects by comparison to other conventional anthropometric methods, as well as air displacement plethysmography, for body fat assessment.

  19. Obesity

    Science.gov (United States)

    ... little free time may have less time to exercise. The term eating disorder means a group of medical conditions that have an unhealthy focus on eating, dieting, losing or gaining weight, and body image. A person may be obese, follow an unhealthy ...

  20. 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...

  1. 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....

  2. 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...

  3. 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...

  4. Physiological models of body composition and human obesity

    OpenAIRE

    Shapses Sue A; Pierson Richard N; Heymsfield Steven B; Levitt David G; Kral John G

    2007-01-01

    Abstract Background The body mass index (BMI) is the standard parameter for predicting body fat fraction and for classifying degrees of obesity. Currently available regression equations between BMI and fat are based on 2 or 3 parameter empirical fits and have not been validated for highly obese subjects. We attempt to develop regression relations that are based on realistic models of body composition changes in obesity. These models, if valid, can then be extrapolated to the high fat fraction...

  5. Expression of Obesity Hormone Leptin in Human Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    Jin-chun Cong; Xian-wei Dai; Ming-yang Shen; Jun-jiang Wang; Chun-sheng Chen; Hong Zhang; Lei Qiao

    2009-01-01

    Objective: The obesity hormone, leptin, has been found to participate in the development and proliferation of normal and malignant tissues. The aim of this study was to evaluate the role of leptin in human colorectal cancer.Methods: Serum leptin levels were measured via ABC-ELLSA in 30 colorectal cancers and 24 normal controls. Leptin concentration in colorectal cancer was analyzed in terms of selected clinicopathological features and some oncogenes.Results: The mean concentration of leptin was significantly higher for colorectal cancers(3.54±1.46 ng/ml) than normal controls(2.27±0.99 ng/ml), no gender difference was observed in this study. Leptin expression in poorly differentiated tumors was obviously lower than those in moderately and well differentiated tumors. There were no statistically significant correlations between leptin and the serum CEA and CA199 in colorectal cancers (P>0.05), and between leptin and the expressions of K-RAS, P53, APC, DCC genes in tumor tissues (P>0.05).Conclusion: Leptin is overexpressed in human colorectal cancer, which is related to the differentiation degrees of the tumor. There is no correlation between leptin expression and chages of oncogenes in colorectal cancers.

  6. Obesity, More than a 'Cosmetic' Problem. Current Knowledge and Future Prospects of Human Obesity Genetics.

    Science.gov (United States)

    Shabana; Hasnain, Shahida

    2016-02-01

    Obesity has been designated as a global epidemic by WHO as its prevalence has increased at an alarming rate in the last few decades worldwide. It is a risk factor for diabetes, hypertension, cardiovascular problems, etc. The contribution of genes to the development of obesity was confirmed in late twentieth century. The concept of monogenic obesity came with the identification of leptin, and mutations in its gene, followed by the discovery of more single gene mutations. However, the recent explosion of obesity could not be explained on the basis of these rare mutations and it was after the first genome-wide association study in 2007 that made possible the identification of different effect size variants in many candidate and non-candidate genes acting in a quantitative way to add to body weight. These studies laid down the basis for polygenic cause of common forms of obesity. The role of epigenetic regulation in the modulation of energy regulation pathway was another important explanation put forward in the latter half of the past decade. Taking into account the quantitative contribution of different variants has given the concept of obesity risk scoring in order to score individuals into different risk groups so as to decide for treatment options.

  7. 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...

  8. 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 compa

  9. 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

  10. Physiological models of body composition and human obesity

    Directory of Open Access Journals (Sweden)

    Shapses Sue A

    2007-09-01

    Full Text Available Abstract Background The body mass index (BMI is the standard parameter for predicting body fat fraction and for classifying degrees of obesity. Currently available regression equations between BMI and fat are based on 2 or 3 parameter empirical fits and have not been validated for highly obese subjects. We attempt to develop regression relations that are based on realistic models of body composition changes in obesity. These models, if valid, can then be extrapolated to the high fat fraction of the morbidly obese. Methods The analysis was applied to 3 compartment (density and total body water measurements of body fat. The data was collected at the New York Obesity Research Center, Body Composition Unit, as part of ongoing studies. A total of 1356 subjects were included, with a BMI range of 17 to 50 for males and 17 to 65 for females. The body composition model assumes that obese subjects can be represented by the sum of a standard lean reference subject plus an extra weight that has a constant adipose, bone and muscle fraction. Results There is marked age and sex dependence in the relationship between BMI and fat fraction. There was no significant difference among Caucasians, Blacks and Hispanics while Asians had significantly greater fat fraction for the same BMI. A linear relationship between BMI and fat fraction provides a good description for men but overestimates the fat fraction in morbidly obese women for whom a non-linear regression should be used. New regression relations for predicting body fat just from experimental measurements of body density are described that are more accurate then those currently used. From the fits to the experimental BMI and density data, a quantitative description of the bone, adipose and muscle body composition of lean and obese subjects is derived. Conclusion Physiologically realistic models of body composition provide both accurate regression relations and new insights about changes in body composition in

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

    Science.gov (United States)

    Cirera, S; Jensen, M S; Elbrønd, V S; Moesgaard, S G; Christoffersen, B Ø; Kadarmideen, H N; Skovgaard, K; Bruun, C V; Karlskov-Mortensen, P; Jørgensen, C B; Fredholm, M

    2014-02-01

    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 receptor (MC4R), fat mass and obesity associated (FTO), neuronal growth regulator 1 (NEGR)1 and adiponectin (ADIPOQ), in seven obesity-relevant tissues (liver; muscle; pancreas; hypothalamus; and retroperitoneal, subcutaneous and mesenteric adipose tissues) in two pig breeds (production pigs and Göttingen 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 shows significant differential expression in all tissues analyzed, and NEGR1 shows significant differential expression in muscle, pancreas, hypothalamus and subcutaneous adipose tissue. The MC4R transcript can be detected only in hypothalamus. In general, the expression profiles of the investigated genes are in accordance with those observed in human studies. Our study shows that both the differences between the investigated breeds and the phenotypic state with respect to obesity/leanness play a large role for differential expression of the obesity-related genes.

  12. The Neuropathology of Obesity: Insights from Human Disease

    OpenAIRE

    Lee, Edward B.; Mark P. Mattson

    2013-01-01

    Obesity, a pathologic state defined by excess adipose tissue, is a significant public health problem as it affects a large proportion of individuals and is linked with increased risk for numerous chronic diseases. Obesity is the result of fundamental changes associated with modern society including overnutrition and sedentary lifestyles. Proper energy homeostasis is dependent on normal brain function as the master metabolic regulator which integrates peripheral signals, modulates autonomic ou...

  13. 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.

  14. Pathophysiology and genetics of obesity and diabetes in the New Zealand obese mouse: a model of the human metabolic syndrome.

    Science.gov (United States)

    Kluge, Reinhart; Scherneck, Stephan; Schürmann, Annette; Joost, Hans-Georg

    2012-01-01

    The New Zealand Obese (NZO) mouse is one of the most thoroughly investigated polygenic models for the human metabolic syndrome and type 2 diabetes. It presents the main characteristics of the disease complex, including early-onset obesity, insulin resistance, dyslipidemia, and hypertension. As a consequence of this syndrome, a combination of lipotoxicity and glucotoxicity produces beta-cell failure and apoptosis resulting in hypoinsulinemia and diabetic hyperglycemia. With NZO as a breeding partner, several adipogenic and diabetogenic gene variants have been identified by hypothesis-free positional cloning (Tbc1d1, Zfp69) or by combining genetic screens and candidate gene approaches (Pctp, Abcg1, Nmur2, Lepr). This chapter summarizes the present knowledge of the NZO strain and describes its pathophysiology as well as the known underlying genetic defects.

  15. Role of PUFAs, the precursors of endocannabinoids, in human obesity and type 2 diabetes.

    Science.gov (United States)

    Dain, Alejandro; Repossi, Gaston; Das, Undurti N; Eynard, Aldo Renato

    2010-06-01

    Polyunsaturated fatty acids (PUFAs) serve as precursors of the endocannabinoids (ECs) that are bioactive lipids molecules. Recent studies revealed that ECs participate in several physiological and pathological processes including obesity and type 2 diabetes mellitus. Here we review the experimental and clinical aspects of the role of endocannabinoids in obesity and type 2 diabetes mellitus and the modification of the endocannabinoids by exogenously administered PUFAs. Based on these evidences, we propose that the endocannabinoid system (ECS) can be modulated by exogenous manipulation of PUFAs that could help in the prevention and management of human diseases such as obesity, metabolic syndrome and type 2 diabetes mellitus.

  16. Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity

    OpenAIRE

    Maria Keller; Lydia Hopp; Xuanshi Liu; Tobias Wohland; Kerstin Rohde; Raffaella Cancello; Matthias Klös; Karl Bacos; Matthias Kern; Fabian Eichelmann; Arne Dietrich; Michael R Schön; Daniel Gärtner; Tobias Lohmann; Miriam Dreßler

    2017-01-01

    Objective/methods: DNA methylation plays an important role in obesity and related metabolic complications. We examined genome-wide DNA promoter methylation along with mRNA profiles in paired samples of human subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from non-obese vs. obese individuals. Results: We identified negatively correlated methylation and expression of several obesity-associated genes in our discovery dataset and in silico replicated ETV6 in two i...

  17. Type 2 diabetes, obesity, and sex difference affect the fate of glucose in the human heart

    OpenAIRE

    Peterson, Linda R.; Herrero, Pilar; Coggan, Andrew R.; Kisrieva-Ware, Zulia; Saeed, Ibrahim; Dence, Carmen; Koudelis, Deborah; McGill, Janet B.; Lyons, Matthew R.; Novak, Eric; Dávila-Román, Víctor G.; Waggoner, Alan D.; Gropler, Robert J.

    2015-01-01

    Type 2 diabetes, obesity, and sex difference affect myocardial glucose uptake and utilization. However, their effect on the intramyocellular fate of glucose in humans has been unknown. How the heart uses glucose is important, because it affects energy production and oxygen efficiency, which in turn affect heart function and adaptability. We hypothesized that type 2 diabetes, sex difference, and obesity affect myocardial glucose oxidation, glycolysis, and glycogen production. In a first-in-hum...

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

    DEFF Research Database (Denmark)

    Tang-Péronard, J L; Andersen, Helle Raun; Jensen, T K

    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...... 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.......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...

  19. 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.

  20. The l-α-Lysophosphatidylinositol/GPR55 System and Its Potential Role in Human Obesity

    Science.gov (United States)

    Moreno-Navarrete, José María; Catalán, Victoria; Whyte, Lauren; Díaz-Arteaga, Adenis; Vázquez-Martínez, Rafael; Rotellar, Fernando; Guzmán, Rocío; Gómez-Ambrosi, Javier; Pulido, Marina R.; Russell, Wendy R.; Imbernón, Mónica; Ross, Ruth A.; Malagón, María M.; Dieguez, Carlos; Fernández-Real, José Manuel; Frühbeck, Gema; Nogueiras, Ruben

    2012-01-01

    GPR55 is a putative cannabinoid receptor, and l-α-lysophosphatidylinositol (LPI) is its only known endogenous ligand. We investigated 1) whether GPR55 is expressed in fat and liver; 2) the correlation of both GPR55 and LPI with several metabolic parameters; and 3) the actions of LPI on human adipocytes. We analyzed CB1, CB2, and GPR55 gene expression and circulating LPI levels in two independent cohorts of obese and lean subjects, with both normal or impaired glucose tolerance and type 2 diabetes. Ex vivo experiments were used to measure intracellular calcium and lipid accumulation. GPR55 levels were augmented in the adipose tissue of obese subjects and further so in obese patients with type 2 diabetes when compared with nonobese subjects. Visceral adipose tissue GPR55 correlated positively with weight, BMI, and percent fat mass, particularly in women. Hepatic GPR55 gene expression was similar in obese and type 2 diabetic subjects. Circulating LPI levels were increased in obese patients and correlated with fat percentage and BMI in women. LPI increased the expression of lipogenic genes in visceral adipose tissue explants and intracellular calcium in differentiated visceral adipocytes. These findings indicate that the LPI/GPR55 system is positively associated with obesity in humans. PMID:22179809

  1. 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. PMID:24761347

  2. 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...... was still lower than that of the control subjects (4.2%, p less than 0.001). The glucose-induced arterial norepinephrine response remained diminished in the reduced obese patients whereas the changes in plasma epinephrine were similar in all three groups. The results suggest that a defective SNS may...

  3. 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

    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...

  4. Adrenergic receptor polymorphisms and autonomic nervous system function in human obesity.

    Science.gov (United States)

    Yasuda, Koichiro; Matsunaga, Tetsuro; Adachi, Tetsuya; Aoki, Norihiko; Tsujimoto, Gozoh; Tsuda, Kinsuke

    2006-09-01

    Adrenergic receptors (ARs) are cell-surface G-protein-coupled receptors for catecholamines. They are essential components of the sympathetic nervous system, organized within the autonomic nervous system (ANS), which controls various physiological functions, including energy homeostasis and metabolism of glucose and lipids. An impairment of ANS function in metabolism is considered to be one of the pathological states associated with human obesity and related metabolic diseases; thus, alterations in AR function might be implicated in the pathophysiology of these diseases. Several studies have suggested an association between obesity phenotypes and some AR polymorphisms. In vitro and human clinical studies indicate that some of these polymorphisms have functional and pathophysiological significance, including the linkage to ANS function. This review summarizes present knowledge of AR polymorphisms related to human obesity, and their association with ANS function.

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

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    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.

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

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    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.

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

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    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

  8. 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

    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......)max) were measured in 10 older (age, 60 +/- 4 years; mean +/- SEM) and 10 younger (age, 35 +/- 4 years) body mass index-matched, obese, normal glucose-tolerant individuals. Fasting blood samples were also collected. Older subjects had slightly elevated fat mass (32.2 +/- 7.1 vs 36.5 +/- 6.7 kg, P...... = .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...

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

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    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 ...

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

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    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.

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

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    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.

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

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    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.

  13. Effect of Bariatric Weight Loss on the Adipose Lipolytic Transcriptome in Obese Humans

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    Shakun Karki

    2015-01-01

    Full Text Available Background. Dysregulated lipolysis has been implicated in mechanisms of cardiometabolic disease and inflammation in obesity. Purpose. We sought to examine the effect of bariatric weight loss on adipose tissue lipolytic gene expression and their relationship to systemic metabolic parameters in obese subjects. Methods/Results. We biopsied subcutaneous adipose tissue in 19 obese individuals (BMI 42 ± 5 kg/m2, 79% female at baseline and after a mean period of 8 ± 5 months (range 3–15 months following bariatric surgery. We performed adipose tissue mRNA expression of proteins involved in triglyceride hydrolysis and correlated their weight loss induced alterations with systemic parameters associated with cardiovascular disease risk. mRNA transcripts of adipose triglyceride lipase (ATGL, hormone-sensitive lipase (HSL, and lipid droplet proteins comparative gene identification 58 (CGI-58 and perilipin increased significantly after weight loss (p<0.05 for all. ATGL expression correlated inversely with plasma triglyceride (TG, hemoglobin A1C (HbA1C, and glucose, and HSL expression correlated negatively with glucose, while CGI-58 was inversely associated with HbA1C. Conclusion. We observed increased expression of adipose tissue lipolytic genes following bariatric weight loss which correlated inversely with systemic markers of lipid and glucose metabolism. Functional alterations in lipolysis in human adipose tissue may play a role in shaping cardiometabolic phenotypes in human obesity.

  14. An integrated approach of comparative genomics and heritability analysis of pig and human on obesity trait: evidence for candidate genes on human chromosome 2

    Science.gov (United States)

    2012-01-01

    Background Traditional candidate gene approach has been widely used for the study of complex diseases including obesity. However, this approach is largely limited by its dependence on existing knowledge of presumed biology of the phenotype under investigation. Our combined strategy of comparative genomics and chromosomal heritability estimate analysis of obesity traits, subscapular skinfold thickness and back-fat thickness in Korean cohorts and pig (Sus scrofa), may overcome the limitations of candidate gene analysis and allow us to better understand genetic predisposition to human obesity. Results We found common genes including FTO, the fat mass and obesity associated gene, identified from significant SNPs by association studies of each trait. These common genes were related to blood pressure and arterial stiffness (P = 1.65E-05) and type 2 diabetes (P = 0.00578). Through the estimation of variance of genetic component (heritability) for each chromosome by SNPs, we observed a significant positive correlation (r = 0.479) between genetic contributions of human and pig to obesity traits. Furthermore, we noted that human chromosome 2 (syntenic to pig chromosomes 3 and 15) was most important in explaining the phenotypic variance for obesity. Conclusions Obesity genetics still awaits further discovery. Navigating syntenic regions suggests obesity candidate genes on chromosome 2 that are previously known to be associated with obesity-related diseases: MRPL33, PARD3B, ERBB4, STK39, and ZNF385B. PMID:23253381

  15. An integrated approach of comparative genomics and heritability analysis of pig and human on obesity trait: evidence for candidate genes on human chromosome 2

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    Kim Jaemin

    2012-12-01

    Full Text Available Abstract Background Traditional candidate gene approach has been widely used for the study of complex diseases including obesity. However, this approach is largely limited by its dependence on existing knowledge of presumed biology of the phenotype under investigation. Our combined strategy of comparative genomics and chromosomal heritability estimate analysis of obesity traits, subscapular skinfold thickness and back-fat thickness in Korean cohorts and pig (Sus scrofa, may overcome the limitations of candidate gene analysis and allow us to better understand genetic predisposition to human obesity. Results We found common genes including FTO, the fat mass and obesity associated gene, identified from significant SNPs by association studies of each trait. These common genes were related to blood pressure and arterial stiffness (P = 1.65E-05 and type 2 diabetes (P = 0.00578. Through the estimation of variance of genetic component (heritability for each chromosome by SNPs, we observed a significant positive correlation (r = 0.479 between genetic contributions of human and pig to obesity traits. Furthermore, we noted that human chromosome 2 (syntenic to pig chromosomes 3 and 15 was most important in explaining the phenotypic variance for obesity. Conclusions Obesity genetics still awaits further discovery. Navigating syntenic regions suggests obesity candidate genes on chromosome 2 that are previously known to be associated with obesity-related diseases: MRPL33, PARD3B, ERBB4, STK39, and ZNF385B.

  16. Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity.

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    Blüher, Matthias; Engeli, Stefan; Klöting, Nora; Berndt, Janin; Fasshauer, Mathias; Bátkai, Sándor; Pacher, Pál; Schön, Michael R; Jordan, Jens; Stumvoll, Michael

    2006-11-01

    The endocannabinoid system has been suspected to contribute to the association of visceral fat accumulation with metabolic diseases. We determined whether circulating endocannabinoids are related to visceral adipose tissue mass in lean, subcutaneous obese, and visceral obese subjects (10 men and 10 women in each group). We further measured expression of the cannabinoid type 1 (CB(1)) receptor and fatty acid amide hydrolase (FAAH) genes in paired samples of subcutaneous and visceral adipose tissue in all 60 subjects. Circulating 2-arachidonoyl glycerol (2-AG) was significantly correlated with body fat (r = 0.45, P = 0.03), visceral fat mass (r = 0.44, P = 0.003), and fasting plasma insulin concentrations (r = 0.41, P = 0.001) but negatively correlated to glucose infusion rate during clamp (r = 0.39, P = 0.009). In visceral adipose tissue, CB(1) mRNA expression was negatively correlated with visceral fat mass (r = 0.32, P = 0.01), fasting insulin (r = 0.48, P endocannabinoid system in human obesity. Thus, the endocannabinoid system may represent a primary target for the treatment of abdominal obesity and associated metabolic changes.

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

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    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.

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

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

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    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

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

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    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.

  1. Zinc-transporter genes in human visceral and subcutaneous adipocytes: lean versus obese.

    Science.gov (United States)

    Smidt, Kamille; Pedersen, Steen B; Brock, Birgitte; Schmitz, Ole; Fisker, Sanne; Bendix, Jørgen; Wogensen, Lise; Rungby, Jørgen

    2007-01-29

    Zinc ions influence adipose tissue metabolism by regulating leptin secretion and by promoting free fatty acid release and glucose uptake. The mechanisms controlling zinc metabolism in adipose tissue are unknown. We therefore examined the gene-expression levels of a number of zinc-transporting proteins in adipose tissue, comparing subcutaneous fat with visceral fat from lean and obese humans. Both ZnT-proteins responsible for zinc transport from cytosol to extracellular compartments and intracellular vesicles and Zip-proteins responsible for zinc transport to the cytoplasm were expressed in all samples. This suggests that zinc metabolism in adipocytes is actively controlled by zinc-transporters. The expression levels were different in lean and obese subjects suggesting a role for these proteins in obesity. Furthermore, the expression levels were different from subcutaneous fat to intra-abdominal fat suggesting that the metabolic activity in adipocytes is to some extent dependent upon zinc and the activity of zinc-transporting proteins or vice versa.

  2. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans.

    Science.gov (United States)

    Rahimi, Mehran; Vinciguerra, Manlio; Daghighi, Mojtaba; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M; Mahmoudi, Morteza; De Rooij, Felix W M; Sijbrands, Eric; Peppelenbosch, Maikel P; Rezaee, Farhad

    2015-10-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs.

  3. Conjugated linoleic acid supplementation for twelve weeks increases lean body mass in obese humans.

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    Steck, Susan E; Chalecki, Allison M; Miller, Paul; Conway, Jason; Austin, Gregory L; Hardin, James W; Albright, Craig D; Thuillier, Philippe

    2007-05-01

    Conjugated linoleic acid (CLA) alters body composition in animal models, but few studies have examined the effects of CLA supplementation on body composition and clinical safety measures in obese humans. In the present study, we performed a randomized, double-blind, placebo-controlled trial to examine the changes in body composition and clinical laboratory values following CLA (50:50 ratio of cis-9, trans-11 and trans-10, cis-12 isomers) supplementation for 12 wk in otherwise healthy obese humans. Forty-eight participants (13 males and 35 females) were randomized to receive placebo (8 g safflower oil/d), 3.2 g/d CLA, or 6.4 g/d CLA for 12 wk. Changes in body fat mass and lean body mass were determined by dual-energy X-ray absorptiometry. Resting energy expenditure was assessed by indirect calorimetry. Clinical laboratory values and adverse-event reporting were used to monitor safety. Lean body mass increased by 0.64 kg in the 6.4 g/d CLA group (P < 0.05) after 12 wk of intervention. Significant decreases in serum HDL-cholesterol and sodium, hemoglobin, and hematocrit, and significant increases in serum alkaline phosphatase, C-reactive protein, and IL-6, and white blood cells occurred in the 6.4 g/d CLA group, although all values remained within normal limits. The intervention was well tolerated and no severe adverse events were reported, although mild gastrointestinal adverse events were reported in all treatment groups. In conclusion, whereas CLA may increase lean body mass in obese humans, it may also increase markers of inflammation in the short term.

  4. A polymorphism in the human agouti-related protein is associated with late-onset obesity.

    Science.gov (United States)

    Argyropoulos, George; Rankinen, Tuomo; Neufeld, Doni R; Rice, Treva; Province, Michael A; Leon, Arthur S; Skinner, James S; Wilmore, Jack H; Rao, D C; Bouchard, Claude

    2002-09-01

    The mouse agouti-related protein (AGRP) is a powerful appetite effector that results in hyperphagia and the development of obesity when administered intracerebroventricularly or when overexpressed in transgenic mice. Animal studies have also shown that exogenous administration of AGRP predisposes toward hedonic intake of high fat and high sucrose diets. The human ortholog (hAGRP) maps on chromosome 16q22 and has similar physiological properties, as tested in animal models. A polymorphism was identified in the third exon of hAGRP, c.199G-->A, that resulted in a nonconservative amino acid substitution, Ala(67)Thr. Computational analysis of the protein showed significant differences in the coils of the two polymorphic isoforms of the protein. Human studies showed no genotype effects in individuals with a mean age of 25 yr. However, the G/G genotype was significantly associated with fatness and abdominal adiposity in the parental population with a mean age of 53 yr. The c.199G-->A polymorphism in hAGRP could, therefore, play a role in the development of human obesity in an age-dependent fashion.

  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

    -wide changes in DNA methylation and expression patterns during differentiation of primary human muscle stem cells (myoblasts). We identified epigenetic and transcriptional changes of myogenic transcription factors (MYOD1, MYOG, MYF5, MYF6, PAX7, MEF2A, MEF2C, and MEF2D), cell cycle regulators, metabolic......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...... enzymes and genes previously not linked to myogenesis, including IL32, metallothioneins, and pregnancy-specific beta-1-glycoproteins. Functional studies demonstrated IL-32 as a novel target that regulates human myogenesis, insulin sensitivity and ATP levels in muscle cells. Furthermore, IL32 transgenic...

  6. Physical Exercise Reduces the Expression of RANTES and Its CCR5 Receptor in the Adipose Tissue of Obese Humans

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    Engin Baturcam

    2014-01-01

    Full Text Available RANTES and its CCR5 receptor trigger inflammation and its progression to insulin resistance in obese. In the present study, we investigated for the first time the effect of physical exercise on the expression of RANTES and CCR5 in obese humans. Fifty-seven adult nondiabetic subjects (17 lean and 40 obese were enrolled in a 3-month supervised physical exercise. RANTES and CCR5 expressions were measured in PBMCs and subcutaneous adipose tissue before and after exercise. Circulating plasma levels of RANTES were also investigated. There was a significant increase in RANTES and CCR5 expression in the subcutaneous adipose tissue of obese compared to lean. In PBMCs, however, while the levels of RANTES mRNA and protein were comparable between both groups, CCR5 mRNA was downregulated in obese subjects (P<0.05. Physical exercise significantly reduced the expression of both RANTES and CCR5 (P<0.05 in the adipose tissue of obese individuals with a concomitant decrease in the levels of the inflammatory markers TNF-α, IL-6, and P-JNK. Circulating RANTES correlated negatively with anti-inflammatory IL-1ra (P=0.001 and positively with proinflammatory IP-10 and TBARS levels (P<0.05. Therefore, physical exercise may provide an effective approach for combating the deleterious effects associated with obesity through RANTES signaling in the adipose tissue.

  7. Reverse relationship between blood boron level and body mass index in humans: does it matter for obesity?

    Science.gov (United States)

    Hasbahceci, Mustafa; Cipe, Gokhan; Kadioglu, Huseyin; Aysan, Erhan; Muslumanoglu, Mahmut

    2013-06-01

    The exact role of boron in humans is not known although its supplementation causes several important metabolic and inflammatory changes. The objective of this study is to evaluate the possibility of an association between blood boron level and obesity in normal, overweight, obese, and morbidly obese subjects. A total number of 80 subjects, categorized into four groups based on their body mass index as normal, overweight, obese, and morbidly obese, were enrolled in this study. Age, sex, body mass index, and blood boron levels were recorded for each subject. Although the distribution of female and male subjects and blood boron levels were similar between groups, the mean age of normal subjects was significantly lower than the others (p = 0.002). There was a significant relationship between age and quantitative values of body mass index for each subject (β = 0.24; p = 0.003). In addition, between blood boron levels and quantitative values of body mass index for each subject, a significant reverse relationship was detected (β = -0.16; p = 0.043). Although age seemed to be an important variable for blood boron level and body mass index, blood boron levels were shown to be lower in obese subjects in comparison to non-obese subjects.

  8. Physical exercise reduces the expression of RANTES and its CCR5 receptor in the adipose tissue of obese humans.

    Science.gov (United States)

    Baturcam, Engin; Abubaker, Jehad; Tiss, Ali; Abu-Farha, Mohamed; Khadir, Abdelkrim; Al-Ghimlas, Fahad; Al-Khairi, Irina; Cherian, Preethi; Elkum, Naser; Hammad, Maha; John, Jeena; Kavalakatt, Sina; Lehe, Cynthia; Warsame, Samia; Behbehani, Kazem; Dermime, Said; Dehbi, Mohammed

    2014-01-01

    RANTES and its CCR5 receptor trigger inflammation and its progression to insulin resistance in obese. In the present study, we investigated for the first time the effect of physical exercise on the expression of RANTES and CCR5 in obese humans. Fifty-seven adult nondiabetic subjects (17 lean and 40 obese) were enrolled in a 3-month supervised physical exercise. RANTES and CCR5 expressions were measured in PBMCs and subcutaneous adipose tissue before and after exercise. Circulating plasma levels of RANTES were also investigated. There was a significant increase in RANTES and CCR5 expression in the subcutaneous adipose tissue of obese compared to lean. In PBMCs, however, while the levels of RANTES mRNA and protein were comparable between both groups, CCR5 mRNA was downregulated in obese subjects (P < 0.05). Physical exercise significantly reduced the expression of both RANTES and CCR5 (P < 0.05) in the adipose tissue of obese individuals with a concomitant decrease in the levels of the inflammatory markers TNF- α , IL-6, and P-JNK. Circulating RANTES correlated negatively with anti-inflammatory IL-1 ra (P = 0.001) and positively with proinflammatory IP-10 and TBARS levels (P < 0.05). Therefore, physical exercise may provide an effective approach for combating the deleterious effects associated with obesity through RANTES signaling in the adipose tissue.

  9. Regulation of nutrition-associated receptors in blood monocytes of normal weight and obese humans.

    Science.gov (United States)

    Pivovarova, Olga; Hornemann, Silke; Weimer, Sandra; Lu, Ye; Murahovschi, Veronica; Zhuk, Sergei; Seltmann, Anne-Cathrin; Malashicheva, Anna; Kostareva, Anna; Kruse, Michael; Busjahn, Andreas; Rudovich, Natalia; Pfeiffer, Andreas F H

    2015-03-01

    Obesity, type 2 diabetes and associated metabolic diseases are characterized by low-grade systemic inflammation which involves interplay of nutrition and monocyte/macrophage functions. We suggested that some factors such as nutrient components, neuropeptides involved in the control of gastrointestinal functions, and gastrointestinal hormones might influence immune cell functions and in this way contribute to the disease pathogenesis. The aim of this study was to investigate the mRNA expression of twelve nutrition-associated receptors in peripheral blood mononuclear cells (PBMC), isolated monocytes and monocyte-derived macrophages and their regulation under the switching from the high-carbohydrate low-fat diet to the low-carbohydrate high-fat (LC/HFD) isocaloric diet in healthy humans. The mRNA expression of receptors for short chain fatty acids (GPR41, GPR43), bile acids (TGR5), incretins (GIPR, GLP1R), cholecystokinin (CCKAR), neuropeptides VIP and PACAP (VIPR1, VIPR2), and neurotensin (NTSR1) was detected in PBMC and monocytes, while GPR41, GPR43, GIPR, TGR5, and VIPR1 were found in macrophages. Correlations of the receptor expression in monocytes with a range of metabolic and inflammatory markers were found. In non-obese subjects, the dietary switch to LC/HFD induced the increase of GPR43 and VIPR1 expression in monocytes. No significant differences of receptor expression between normal weight and moderately obese subjects were found. Our study characterized for the first time the expression pattern of nutrition-associated receptors in human blood monocytes and its dietary-induced changes linking metabolic responses to nutrition with immune functions in health and metabolic diseases.

  10. 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.

  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. Current review of genetics of human obesity: from molecular mechanisms to an evolutionary perspective.

    Science.gov (United States)

    Albuquerque, David; Stice, Eric; Rodríguez-López, Raquel; Manco, Licíno; Nóbrega, Clévio

    2015-08-01

    It is well-known that obesity is a complex multifactorial and heterogeneous condition with an important genetic component. Recently, major advances in obesity research emerged concerning the molecular mechanisms contributing to the obese condition. This review outlines several studies and data concerning the genetics and other important factors in the susceptibility risk to develop obesity. Based in the genetic etiology three main categories of obesity are considered: monogenic, syndromic, and common obesity. For the monogenic forms of obesity, the gene causing the phenotype is clearly identified, whereas for the common obesity the loci architecture underlying the phenotype is still being characterized. Given that, in this review we focus mainly in this obesity form, reviewing loci found until now by genome-wide association studies related with the susceptibility risk to develop obesity. Moreover, we also detail the obesity-related loci identified in children and in different ethnic groups, trying to highlight the complexity of the genetics underlying the common obese phenotype. Importantly, we also focus in the evolutionary hypotheses that have been proposed trying to explain how natural selection favored the spread of genes that increase the risk for an obese phenotype and how this predisposition to obesity evolved. Other factors are important in the obesity condition, and thus, we also discuss the epigenetic mechanisms involved in the susceptibility and development of obesity. Covering all these topics we expect to provide a complete and recent perspective about the underlying mechanisms involved in the development and origin of obesity. Only with a full understanding of the factors and mechanisms contributing to obesity, it will be possible to provide and allow the development of new therapeutic approaches to this condition.

  13. Dietary supplementation with purified citrus limonin glucoside does not alter ex vivo functions of circulating T lymphocytes or monocytes in overweight/obese human adults

    Science.gov (United States)

    Overweight/obesity is associated with chronic inflammation and impairs both innate and adaptive immune responses. Limonoids found in citrus fruits have shown health benefits in human and animal studies. In a double-blind, randomized, crossover study, 10 overweight/obese human subjects were fed pur...

  14. Exercise-mediated vasodilation in human obesity and metabolic syndrome: effect of acute ascorbic acid infusion

    Science.gov (United States)

    Limberg, Jacqueline K.; Kellawan, J. Mikhail; Harrell, John W.; Johansson, Rebecca E.; Eldridge, Marlowe W.; Proctor, Lester T.; Sebranek, Joshua J.

    2014-01-01

    We tested the hypothesis that infusion of ascorbic acid (AA), a potent antioxidant, would alter vasodilator responses to exercise in human obesity and metabolic syndrome (MetSyn). Forearm blood flow (FBF, Doppler ultrasound) was measured in lean, obese, and MetSyn adults (n = 39, 32 ± 2 yr). A brachial artery catheter was inserted for blood pressure monitoring and local infusion of AA. FBF was measured during dynamic handgrip exercise (15% maximal effort) with and without AA infusion. To account for group differences in blood pressure and forearm size, and to assess vasodilation, forearm vascular conductance (FVC = FBF/mean arterial blood pressure/lean forearm mass) was calculated. We examined the time to achieve steady-state FVC (mean response time, MRT) and the rise in FVC from rest to steady-state exercise (Δ, exercise − rest) before and during acute AA infusion. The MRT (P = 0.26) and steady-state vasodilator responses to exercise (ΔFVC, P = 0.31) were not different between groups. Intra-arterial infusion of AA resulted in a significant increase in plasma total antioxidant capacity (174 ± 37%). AA infusion did not alter MRT or steady-state FVC in any group (P = 0.90 and P = 0.85, respectively). Interestingly, higher levels of C-reactive protein predicted longer MRT (r = 0.52, P < 0.01) and a greater reduction in MRT with AA infusion (r = −0.43, P = 0.02). We concluded that AA infusion during moderate-intensity, rhythmic forearm exercise does not alter the time course or magnitude of exercise-mediated vasodilation in groups of young lean, obese, or MetSyn adults. However, systemic inflammation may limit the MRT to exercise, which can be improved with AA. PMID:25038148

  15. 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.

  16. 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.

  17. 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

    /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 to type II fibers have higher protein levels of the insulin receptor, GLUT4......-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......, hexokinase II, glycogen synthase (GS), pyruvate dehydrogenase (PDH-E1α) and a lower protein content of Akt2, TBC1D4 and TBC1D1. In type I fibers compared to type II fibers, the phosphorylation-response to insulin was similar (TBC1D4, TBC1D1 and GS) or decreased (Akt and PDH-E1α). Phosphorylation...

  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 m

  19. The influence of insulin on the raised plasma fibronectin concentration in human obesity

    DEFF Research Database (Denmark)

    Dejgård, A; Andersen, T; Gluud, C

    1986-01-01

    in the controls (obese r = 0.06, controls r = 0.02; p greater than 0.05). Plasma fibronectin was insignificantly correlated with body weight (obese r = 0.21, controls r = 0.15; p greater than 0.05) and percentage overweight (obese r = 0.27, controls r = 0.04; p greater than 0.05). The raised level of circulating...... insulin may in part explain the excess of plasma fibronectin obese subjects....

  20. 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....... Thus many genetic variants controlling obesity remain to be identified. The aim of this study was to use GWA followed by multiple stepwise validations to identify additional genes associated with obesity....

  1. 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

  2. The circulatory and metabolic responses to hypoxia in humans - with special reference to adipose tissue physiology and obesity

    NARCIS (Netherlands)

    I. Heinonen (Ilkka); R. Boushel (Robert); K.K. Kalliokoski (Kari)

    2016-01-01

    textabstractAdipose tissue metabolism and circulation play an important role in human health. It is well-known that adipose tissue mass is increased in response to excess caloric intake leading to obesity and further to local hypoxia and inflammatory signaling. Acute exercise increases blood supply

  3. 21 CFR 250.11 - Thyroid-containing drug preparations intended for treatment of obesity in humans.

    Science.gov (United States)

    2010-04-01

    ... nervous system stimulants, with or without one or more additional drug substances such as barbiturates or.... (b) Combinations of thyroid or other thyrogenic drugs with central nervous system stimulants with or... treatment of obesity in humans. 250.11 Section 250.11 Food and Drugs FOOD AND DRUG...

  4. You are what you eat, or are you? The challenges of translating high-fat-fed rodents to human obesity and diabetes.

    Science.gov (United States)

    Lai, M; Chandrasekera, P C; Barnard, N D

    2014-09-08

    Obesity and type 2 diabetes mellitus (T2DM) are rapidly growing worldwide epidemics with major health consequences. Various human-based studies have confirmed that both genetic and environmental factors (particularly high-caloric diets and sedentary lifestyle) greatly contribute to human T2DM. Interactions between obesity, insulin resistance and β-cell dysfunction result in human T2DM, but the mechanisms regulating the interplay among these impairments remain unclear. Rodent models of high-fat diet (HFD)-induced obesity have been used widely to study human obesity and T2DM. With >9000 publications on PubMed over the past decade alone, many aspects of rodent T2DM have been elucidated; however, correlation to human obesity/diabetes remains poor. This review investigates the reasons for this translational discrepancy by critically evaluating rodent HFD models. Dietary modification in rodents appears to have limited translatable benefit for understanding and treating human obesity and diabetes due-at least in part-to divergent dietary compositions, species/strain and gender variability, inconsistent disease penetrance, severity and duration and lack of resemblance to human obesogenic pathophysiology. Therefore future research efforts dedicated to acquiring translationally relevant data-specifically human data, rather than findings based on rodent studies-would accelerate our understanding of disease mechanisms and development of therapeutics for human obesity/T2DM.

  5. 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

  6. Role of the autonomic nervous system and neuropeptides in the development of obesity in humans: targets for therapy?

    Science.gov (United States)

    Greenfield, Jerry R; Campbell, Lesley V

    2008-01-01

    Obesity and type 2 diabetes have reached epidemic proportions worldwide. These metabolic disorders, particularly obesity, are characterised by increased basal sympathetic nervous system (SNS) activity but an impaired sympathetic response to certain stimuli, such as insulin. Although targeting the SNS may seem an attractive avenue for the pharmacological prevention and treatment of obesity and related metabolic disorders, it remains unknown whether changes in SNS tone are primary and contribute to the development of these metabolic conditions or whether they develop secondary to the obese state. This question can be answered by the study of insulin-resistant individuals prior to the development of obesity and type 2 diabetes. Using this model, it has been shown that early insulin resistance is associated with increased SNS activity in genetically-predisposed humans. It has been suggested that in insulin-resistant states, hyperinsulinaemia is the initiating factor that increases sympathetic neural activity. Over time, adrenoreceptor down-regulation and/or reduced sensitivity are likely to develop, resulting in reduced sympathetic responsiveness. In the postprandial state, this will lead to impaired diet-induced thermogenesis and post-prandial fat oxidation, promoting the accumulation of body fat. More recent evidence demonstrates that stress-induced SNS overactivity up-regulates Neuropeptide Y, an orexigenic hormone, and its Y2 receptor, in visceral adipose tissue, the fat depot most strongly linked to insulin resistance and type 2 diabetes. There is evidence that SNS overactivity specifically contributes to the development of abdominal obesity via this pathway, which could represent a novel target for the prevention and treatment of abdominal obesity and related metabolic consequences.

  7. 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

  8. Potential Epigenetic Biomarkers of Obesity Related Insulin Resistance in Human Whole-blood.

    Science.gov (United States)

    Day, Samantha E; Coletta, Richard L; Kim, Joon Young; Garcia, Luis A; Campbell, Latoya E; Benjamin, Tonya R; Roust, Lori R; De Filippis, Elena A; Mandarino, Lawrence J; Coletta, Dawn K

    2017-01-20

    Obesity can increase the risk of complex metabolic diseases, including insulin resistance. Moreover, obesity can be caused by environmental and genetic factors. However, the epigenetic mechanisms of obesity are not well defined. Therefore, the identification of novel epigenetic biomarkers of obesity allows for a more complete understanding of the disease and its underlying insulin resistance. The aim of our study was to identify DNA methylation changes in whole-blood that were strongly associated with obesity and insulin resistance. Whole-blood was obtained from lean (n = 10; BMI = 23.6 ± 0.7 kg/m(2)) and obese (n = 10; BMI = 34.4 ± 1.3 kg/m(2)) participants in combination with euglycemic hyperinsulinemic clamps to assess insulin sensitivity. We performed reduced representation bisulfite sequencing on genomic DNA isolated from the blood. We identified 49 differentially methylated cytosines (DMCs; qobese compared to lean participants. We identified two sites (Chr.21:46,957,981 and Chr.21:46,957,915) in the 5' untranslated region of solute carrier family 19 member 1 (SLC19A1) with decreased in methylation in obese participants (lean 0.73 ± 0.11 vs. obese 0.09 ± 0.05; lean 0.68 ± 0.10 vs. obese 0.09 ± 0.05, respectively). These two DMCs identified by obesity were also significantly predicted by insulin sensitivity (r = 0.68, P = 0.003; r = 0.66; P = 0.004). In addition, we performed a differentially methylated region (DMR) analysis and demonstrated a decrease in methylation of Chr.21:46,957,915-46,958,001 in SLC19A1 of -34.9% (70.4% lean vs. 35.5% obese). The decrease in whole-blood SLC19A1 methylation in our obese participants was similar to the change observed in skeletal muscle (Chr.21:46,957,981, lean 0.70 ± 0.09 vs. obese 0.31 ± 0.11 and Chr.21:46,957,915, lean 0.72 ± 0.11 vs. obese 0.31 ± 0.13). Pyrosequencing analysis further demonstrated a decrease in methylation at Chr.21:46,957,915 in both whole-blood (lean 0.71 ± 0.10 vs. obese 0.18 ± 0

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

    OpenAIRE

    Pardis Pedram; Guang Sun

    2014-01-01

    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 73...

  10. 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...

  11. 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...... were recruited. Global DNA methylation levels were measured in a cell type-specific manner by flow cytometry. We validated the assay against mass spectrometry measures of the total 5-methylcytosine content in cultured cells treated with the hypomethylation agent decitabine (r = 0.97, p ....001). Results Global DNA methylation in peripheral blood mononuclear cells, monocytes, lymphocytes or T cells was not altered in obese or T2D subjects. However, analysis of blood fractions from lean, obese, and T2D subjects showed increased methylation levels in B cells from obese and T2D subjects...

  12. Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity.

    Science.gov (United States)

    Pigeyre, Marie; Yazdi, Fereshteh T; Kaur, Yuvreet; Meyre, David

    2016-06-01

    In high-, middle- and low-income countries, the rising prevalence of obesity is the underlying cause of numerous health complications and increased mortality. Being a complex and heritable disorder, obesity results from the interplay between genetic susceptibility, epigenetics, metagenomics and the environment. Attempts at understanding the genetic basis of obesity have identified numerous genes associated with syndromic monogenic, non-syndromic monogenic, oligogenic and polygenic obesity. The genetics of leanness are also considered relevant as it mirrors some of obesity's aetiologies. In this report, we summarize ten genetically elucidated obesity syndromes, some of which are involved in ciliary functioning. We comprehensively review 11 monogenic obesity genes identified to date and their role in energy maintenance as part of the leptin-melanocortin pathway. With the emergence of genome-wide association studies over the last decade, 227 genetic variants involved in different biological pathways (central nervous system, food sensing and digestion, adipocyte differentiation, insulin signalling, lipid metabolism, muscle and liver biology, gut microbiota) have been associated with polygenic obesity. Advances in obligatory and facilitated epigenetic variation, and gene-environment interaction studies have partly accounted for the missing heritability of obesity and provided additional insight into its aetiology. The role of gut microbiota in obesity pathophysiology, as well as the 12 genes associated with lipodystrophies is discussed. Furthermore, in an attempt to improve future studies and merge the gap between research and clinical practice, we provide suggestions on how high-throughput '-omic' data can be integrated in order to get closer to the new age of personalized medicine.

  13. The non-obese diabetic (NOD) mouse as a model of human type 1 diabetes.

    Science.gov (United States)

    Kachapati, Kritika; Adams, David; Bednar, Kyle; Ridgway, William M

    2012-01-01

    The non-obese diabetic (NOD) mouse spontaneously develops type 1 diabetes (T1D) and has thus served as a model for understanding the genetic and immunological basis, and treatment, of T1D. Since its initial description in 1980, however, the field has matured and recognized that prevention of diabetes in NOD mice (i.e., preventing the disease from occurring by an intervention prior to frank diabetes) is relatively easy to achieve and does not correlate well with curing the disease (after the onset of frank hyperglycemia). Hundreds of papers have described the prevention of diabetes in NOD mice but only a handful have described its actual reversal. The paradoxical conclusion is that preventing the disease in NOD mice does not necessarily tell us what caused the disease nor how to reverse it. The NOD mouse model is therefore best used now, with respect to human disease, as a way to understand the genetic and immunologic causes of and as a model for trying to reverse disease once hyperglycemia occurs. We describe how genetic approaches to identifying causative gene variants can be adapted to identify novel therapeutic agents for reversing new-onset T1D.

  14. Foodborne transmission of bovine spongiform encephalopathy to non-human primates results in preclinical rapid-onset obesity.

    Directory of Open Access Journals (Sweden)

    Alexander Strom

    Full Text Available Obesity has become one of the largest public health challenges worldwide. Recently, certain bacterial and viral pathogens have been implicated in the pathogenesis of obesity. In the present study, we retrospectively analyzed clinical data, plasma samples and post-mortem tissue specimens derived from a risk assessment study in bovine spongiform encephalopathy (BSE-infected female cynomolgus monkeys (Macaca fascicularis. The original study design aimed to determine minimal infectious doses after oral or intracerebral (i.c. infection of macaques to assess the risk for humans. High-dose exposures resulted in 100% attack rates and a median incubation time of 4.7 years as described previously. Retrospective analyses of clinical data from high-dosed macaques revealed that foodborne BSE transmission caused rapid weight gain within 1.5 years post infection (β = 0.915; P<0.0001 which was not seen in age- and sex-matched control animals or i.c. infected animals. The rapid-onset obesity was not associated with impaired pancreatic islet function or glucose metabolism. In the early preclinical phase of oral transmission associated with body weight gain, prion accumulation was confined to the gastrointestinal tract. Intriguingly, immunohistochemical findings suggest that foodborne BSE transmission has a pathophysiological impact on gut endocrine cells which may explain rapid weight gain. To our knowledge, this is the first experimental model which clearly demonstrates that foodborne pathogens can induce obesity.

  15. Foodborne transmission of bovine spongiform encephalopathy to non-human primates results in preclinical rapid-onset obesity.

    Science.gov (United States)

    Strom, Alexander; Yutzy, Barbara; Kruip, Carina; Ooms, Mark; Schloot, Nanette C; Roden, Michael; Scott, Fraser W; Loewer, Johannes; Holznagel, Edgar

    2014-01-01

    Obesity has become one of the largest public health challenges worldwide. Recently, certain bacterial and viral pathogens have been implicated in the pathogenesis of obesity. In the present study, we retrospectively analyzed clinical data, plasma samples and post-mortem tissue specimens derived from a risk assessment study in bovine spongiform encephalopathy (BSE)-infected female cynomolgus monkeys (Macaca fascicularis). The original study design aimed to determine minimal infectious doses after oral or intracerebral (i.c.) infection of macaques to assess the risk for humans. High-dose exposures resulted in 100% attack rates and a median incubation time of 4.7 years as described previously. Retrospective analyses of clinical data from high-dosed macaques revealed that foodborne BSE transmission caused rapid weight gain within 1.5 years post infection (β = 0.915; P<0.0001) which was not seen in age- and sex-matched control animals or i.c. infected animals. The rapid-onset obesity was not associated with impaired pancreatic islet function or glucose metabolism. In the early preclinical phase of oral transmission associated with body weight gain, prion accumulation was confined to the gastrointestinal tract. Intriguingly, immunohistochemical findings suggest that foodborne BSE transmission has a pathophysiological impact on gut endocrine cells which may explain rapid weight gain. To our knowledge, this is the first experimental model which clearly demonstrates that foodborne pathogens can induce obesity.

  16. Role of n-3 Polyunsaturated Fatty Acids in Ameliorating the Obesity-Induced Metabolic Syndrome in Animal Models and Humans

    Directory of Open Access Journals (Sweden)

    Chao-Wei Huang

    2016-10-01

    Full Text Available The incidence of obesity and its comorbidities, such as insulin resistance and type II diabetes, are increasing dramatically, perhaps caused by the change in the fatty acid composition of common human diets. Adipose tissue plays a role as the major energy reservoir in the body. An excess of adipose mass accumulation caused by chronic positive energy balance results in obesity. The n-3 polyunsaturated fatty acids (n-3 PUFA, DHA (docosahexaenoic acid and EPA (eicosapentaenoic acid exert numerous beneficial effects to maintain physiological homeostasis. In the current review, the physiology of n-3 PUFA effects in the body is delineated from studies conducted in both human and animal experiments. Although mechanistic studies in human are limited, numerous studies conducted in animals and models in vitro provide potential molecular mechanisms of the effects of these fatty acids. Three aspects of n-3 PUFA in adipocyte regulation are discussed: (1 lipid metabolism, including adipocyte differentiation, lipolysis and lipogenesis; (2 energy expenditure, such as mitochondrial and peroxisomal fatty acid β-oxidation; and (3 inflammation, including adipokines and specialized pro-resolving lipid mediators. Additionally, the mechanisms by which n-3 PUFA regulate gene expression are highlighted. The beneficial effects of n-3 PUFA may help to reduce the incidence of obesity and its comorbidities.

  17. Role of n-3 Polyunsaturated Fatty Acids in Ameliorating the Obesity-Induced Metabolic Syndrome in Animal Models and Humans

    Science.gov (United States)

    Huang, Chao-Wei; Chien, Yi-Shan; Chen, Yu-Jen; Ajuwon, Kolapo M.; Mersmann, Harry M.; Ding, Shih-Torng

    2016-01-01

    The incidence of obesity and its comorbidities, such as insulin resistance and type II diabetes, are increasing dramatically, perhaps caused by the change in the fatty acid composition of common human diets. Adipose tissue plays a role as the major energy reservoir in the body. An excess of adipose mass accumulation caused by chronic positive energy balance results in obesity. The n-3 polyunsaturated fatty acids (n-3 PUFA), DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) exert numerous beneficial effects to maintain physiological homeostasis. In the current review, the physiology of n-3 PUFA effects in the body is delineated from studies conducted in both human and animal experiments. Although mechanistic studies in human are limited, numerous studies conducted in animals and models in vitro provide potential molecular mechanisms of the effects of these fatty acids. Three aspects of n-3 PUFA in adipocyte regulation are discussed: (1) lipid metabolism, including adipocyte differentiation, lipolysis and lipogenesis; (2) energy expenditure, such as mitochondrial and peroxisomal fatty acid β-oxidation; and (3) inflammation, including adipokines and specialized pro-resolving lipid mediators. Additionally, the mechanisms by which n-3 PUFA regulate gene expression are highlighted. The beneficial effects of n-3 PUFA may help to reduce the incidence of obesity and its comorbidities. PMID:27735847

  18. 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 foods for reversing metabolic defects in obesity.......Objective: To determine the influence of dietary glycemic index on exercise training-induced adaptations in substrate oxidation in obesity. Design and Methods: Twenty older, obese individuals undertook 3 months of fully supervised aerobic exercise and were randomized to low- (LoGIX) or high....... Results: Weight loss (-8.6 ± 1.1%) and improvements (P fasting lipemia, and metabolic flexibility were similar for both LoGIX and HiGIX groups. During submaximal exercise, energy expenditure was higher following the intervention (P

  19. 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.

  20. Downregulation of STEAP4, a highly-expressed TNF-α-inducible gene in adipose tissue, is associated with obesity in humans

    Institute of Scientific and Technical Information of China (English)

    Chun-mei ZHANG; Xia CHI; Bin WANG; Min ZHANG; Yu-hui NI; Rong-hua CHEN; Xiao-nan LI; Xi-rong GUO

    2008-01-01

    Aim: To determine the relationship between six-transmembrane epithelial antigen of the prostate 4 (STEAP4) expression and obesity. Methods: RT-PCR and immunoblot analyses were performed to determine the differential expressions of STEAP4 mRNA and protein, respectively, in human omental adipose tissue from obese patients and normal weight controls. The expression pattern of STEAP4 mRNA in various human tissues was determined by RT-PCR. The subcellular localization of the STEAP4 protein in human adipose tissue was confirmed by immunohistochemistry. Finally, we confirmed that cultured human omental adi- pose tissue undergoes TNF-α-mediated regulation of the STEAP4 expression.Results: STEAP4 mRNA and protein levels were downregulated in omental adi-pose tissue from obese patients relative to normal controls. The STEAP4 expres-sion was most abundant in human adipose tissue. An immunohistochemical analy-sis confirmed that STEAP4 was associated with the plasma membrane of adipocytes. The STEAP4 expression was induced by TNF-α in a dose-dependent manner in human adipose tissue. Conclusion: STEAP4 was abundantly expressed in human adipose tissue, and the STEAP4 expression was significantly downregulated in obese patients. STEAP4 localized to the plasma membrane of adipocytes, and the STEAP4 expression was induced by TNF-α in adipose tissue.These data suggest that STEAP4 may play a significant role in the development of human obesity.

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

    Science.gov (United States)

    Mariman, Edwin C M; Szklarczyk, Radek; Bouwman, Freek G; Aller, Erik E J G; van Baak, Marleen A; Wang, Ping

    2015-07-01

    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 kg/m(2)) shows that predicted damaging missense variants in olfactory receptor genes on chromosome 1q and rare predicted damaging variants in the protocadherin (PCDH) beta-cluster genes on chromosome 5q31, reported in our previous work, co-localize in subjects with extreme obesity. This implies a synergistic effect between genetic variation in these gene clusters in the predisposition to extreme obesity. Evidence for a general involvement of the olfactory transduction pathway on itself could not be found. Bioinformatic analysis indicates a specific involvement of the PCDH beta-cluster genes in controlling tissue development. Further mechanistic insight needs to await the identification of the ligands of the 1q olfactory receptors. Eventually, this may provide the possibility to manipulate food flavor in a way to reduce the risk of overeating and of extreme obesity in genetically predisposed subjects.

  2. 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.

  3. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain

    DEFF Research Database (Denmark)

    Olesen, R H; Hyde, T M; Kleinman, J E

    2016-01-01

    The incidence of Alzheimer's disease (AD) is increasing. Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia. Obese and diabetic individuals are prone to decreased circulating levels of zinc, reducing the amount of zinc...... available for crucial intracellular processes. In the brain, zinc co-localizes with glutamate in synaptic vesicles, and modulates NMDA receptor activity. Intracellular zinc is involved in apoptosis and fluctuations in cytoplasmic Zn(2+) affect modulation of intracellular signaling. The ZNT and ZIP proteins...... participate in intracellular zinc homeostasis. Altered expression of zinc-regulatory proteins has been described in AD patients. Using microarray data from human frontal cortex (BrainCloud), this study investigates expression of the SCLA30A (ZNT) and SCLA39A (ZIP) families of genes in a Caucasian and African...

  4. The Circulatory and Metabolic Responses to Hypoxia in Humans – With Special Reference to Adipose Tissue Physiology and Obesity

    Science.gov (United States)

    Heinonen, Ilkka H. A.; Boushel, Robert; Kalliokoski, Kari K.

    2016-01-01

    Adipose tissue metabolism and circulation play an important role in human health. It is well-known that adipose tissue mass is increased in response to excess caloric intake leading to obesity and further to local hypoxia and inflammatory signaling. Acute exercise increases blood supply to adipose tissue and mobilization of fat stores for energy. However, acute exercise during systemic hypoxia reduces subcutaneous blood flow in healthy young subjects, but the response in overweight or obese subjects remains to be investigated. Emerging evidence also indicates that exercise training during hypoxic exposure may provide additive benefits with respect to many traditional cardiovascular risk factors as compared to exercise performed in normoxia, but unfavorable effects of hypoxia have also been documented. These topics will be covered in this brief review dealing with hypoxia and adipose tissue physiology. PMID:27621722

  5. Prostaglandin E2 Exerts Multiple Regulatory Actions on Human Obese Adipose Tissue Remodeling, Inflammation, Adaptive Thermogenesis and Lipolysis.

    Directory of Open Access Journals (Sweden)

    Verónica García-Alonso

    Full Text Available Obesity induces white adipose tissue (WAT dysfunction characterized by unremitting inflammation and fibrosis, impaired adaptive thermogenesis and increased lipolysis. Prostaglandins (PGs are powerful lipid mediators that influence the homeostasis of several organs and tissues. The aim of the current study was to explore the regulatory actions of PGs in human omental WAT collected from obese patients undergoing laparoscopic bariatric surgery. In addition to adipocyte hypertrophy, obese WAT showed remarkable inflammation and total and pericellular fibrosis. In this tissue, a unique molecular signature characterized by altered expression of genes involved in inflammation, fibrosis and WAT browning was identified by microarray analysis. Targeted LC-MS/MS lipidomic analysis identified increased PGE2 levels in obese fat in the context of a remarkable COX-2 induction and in the absence of changes in the expression of terminal prostaglandin E synthases (i.e. mPGES-1, mPGES-2 and cPGES. IPA analysis established PGE2 as a common top regulator of the fibrogenic/inflammatory process present in this tissue. Exogenous addition of PGE2 significantly reduced the expression of fibrogenic genes in human WAT explants and significantly down-regulated Col1α1, Col1α2 and αSMA in differentiated 3T3 adipocytes exposed to TGF-β. In addition, PGE2 inhibited the expression of inflammatory genes (i.e. IL-6 and MCP-1 in WAT explants as well as in adipocytes challenged with LPS. PGE2 anti-inflammatory actions were confirmed by microarray analysis of human pre-adipocytes incubated with this prostanoid. Moreover, PGE2 induced expression of brown markers (UCP1 and PRDM16 in WAT and adipocytes, but not in pre-adipocytes, suggesting that PGE2 might induce the trans-differentiation of adipocytes towards beige/brite cells. Finally, PGE2 inhibited isoproterenol-induced adipocyte lipolysis. Taken together, these findings identify PGE2 as a regulator of the complex network of

  6. Prostaglandin E2 Exerts Multiple Regulatory Actions on Human Obese Adipose Tissue Remodeling, Inflammation, Adaptive Thermogenesis and Lipolysis

    Science.gov (United States)

    García-Alonso, Verónica; Titos, Esther; Alcaraz-Quiles, Jose; Rius, Bibiana; Lopategi, Aritz; López-Vicario, Cristina; Jakobsson, Per-Johan; Delgado, Salvadora; Lozano, Juanjo; Clària, Joan

    2016-01-01

    Obesity induces white adipose tissue (WAT) dysfunction characterized by unremitting inflammation and fibrosis, impaired adaptive thermogenesis and increased lipolysis. Prostaglandins (PGs) are powerful lipid mediators that influence the homeostasis of several organs and tissues. The aim of the current study was to explore the regulatory actions of PGs in human omental WAT collected from obese patients undergoing laparoscopic bariatric surgery. In addition to adipocyte hypertrophy, obese WAT showed remarkable inflammation and total and pericellular fibrosis. In this tissue, a unique molecular signature characterized by altered expression of genes involved in inflammation, fibrosis and WAT browning was identified by microarray analysis. Targeted LC-MS/MS lipidomic analysis identified increased PGE2 levels in obese fat in the context of a remarkable COX-2 induction and in the absence of changes in the expression of terminal prostaglandin E synthases (i.e. mPGES-1, mPGES-2 and cPGES). IPA analysis established PGE2 as a common top regulator of the fibrogenic/inflammatory process present in this tissue. Exogenous addition of PGE2 significantly reduced the expression of fibrogenic genes in human WAT explants and significantly down-regulated Col1α1, Col1α2 and αSMA in differentiated 3T3 adipocytes exposed to TGF-β. In addition, PGE2 inhibited the expression of inflammatory genes (i.e. IL-6 and MCP-1) in WAT explants as well as in adipocytes challenged with LPS. PGE2 anti-inflammatory actions were confirmed by microarray analysis of human pre-adipocytes incubated with this prostanoid. Moreover, PGE2 induced expression of brown markers (UCP1 and PRDM16) in WAT and adipocytes, but not in pre-adipocytes, suggesting that PGE2 might induce the trans-differentiation of adipocytes towards beige/brite cells. Finally, PGE2 inhibited isoproterenol-induced adipocyte lipolysis. Taken together, these findings identify PGE2 as a regulator of the complex network of interactions

  7. Modulation of fatty acid transport and metabolism by maternal obesity in the human full-term placenta.

    Science.gov (United States)

    Dubé, Evemie; Gravel, Ariane; Martin, Coralie; Desparois, Guillaume; Moussa, Issa; Ethier-Chiasson, Maude; Forest, Jean-Claude; Giguère, Yves; Masse, André; Lafond, Julie

    2012-07-01

    Knowledge of the consequences of maternal obesity in human placental fatty acids (FA) transport and metabolism is limited. Animal studies suggest that placental uptake of maternal FA is altered by maternal overnutrition. We hypothesized that high maternal body mass index (BMI) affects human placental FA transport by modifying expression of key transporters. Full-term placentas were obtained by vaginal delivery from normal weight (BMI, 18.5-24.9 kg/m(2)) and obese (BMI > 30 kg/m(2)) women. Blood samples were collected from the mother at each trimester and from cord blood at delivery. mRNA and protein expression levels were evaluated with real-time RT-PCR and Western blotting. Lipoprotein lipase (LPL) activity was evaluated using enzyme fluorescence. In vitro linoleic acid transport was studied with isolated trophoblasts. Our results demonstrated that maternal obesity is associated with increased placental weight, decreased gestational age, decreased maternal high-density lipoprotein (HDL) levels during the first and third trimesters, increased maternal triglyceride levels during the second and third trimesters, and increased maternal T3 levels during all trimesters, and decreased maternal cholesterol (CHOL) and low-density lipoprotein (LDL) levels during the third trimester; and increased newborn CHOL, LDL, apolipoprotein B100, and T3 levels. Increases in placental CD36 mRNA and protein expression levels, decreased SLC27A4 and FABP1 mRNA and protein and FABP3 protein expression, and increased LPL activity and decreased villus cytotrophoblast linoleic acid transport were also observed. No changes were seen in expression of PPARA, PPARD, or PPARG mRNA and protein. Overall this study demonstrated that maternal obesity impacts placental FA uptake without affecting fetal growth. These changes, however, could modify the fetus metabolism and its predisposition to develop diseases later in life.

  8. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain.

    Science.gov (United States)

    Olesen, R H; Hyde, T M; Kleinman, J E; Smidt, K; Rungby, J; Larsen, A

    2016-06-14

    The incidence of Alzheimer's disease (AD) is increasing. Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia. Obese and diabetic individuals are prone to decreased circulating levels of zinc, reducing the amount of zinc available for crucial intracellular processes. In the brain, zinc co-localizes with glutamate in synaptic vesicles, and modulates NMDA receptor activity. Intracellular zinc is involved in apoptosis and fluctuations in cytoplasmic Zn(2+) affect modulation of intracellular signaling. The ZNT and ZIP proteins participate in intracellular zinc homeostasis. Altered expression of zinc-regulatory proteins has been described in AD patients. Using microarray data from human frontal cortex (BrainCloud), this study investigates expression of the SCLA30A (ZNT) and SCLA39A (ZIP) families of genes in a Caucasian and African-American sample of 145 neurologically and psychiatrically normal individuals. Expression of ZNT3 and ZNT4 were significantly reduced with increasing age, whereas expression of ZIP1, ZIP9 and ZIP13 were significantly increased. Increasing body mass index (BMI) correlated with a significant reduction in ZNT1 expression similar to what is seen in the early stages of AD. Increasing BMI also correlated with reduced expression of ZNT6. In conclusion, we found that the expression of genes that regulate intracellular zinc homeostasis in the human frontal cortex is altered with increasing age and affected by increasing BMI. With the increasing rates of obesity throughout the world, these findings warrant continuous scrutiny of the long-term consequences of obesity on brain function and the development of neurodegenerative diseases.

  9. Is there a relationship between dietary MSG and [corrected] obesity in animals or humans?

    Science.gov (United States)

    Brosnan, John T; Drewnowski, Adam; Friedman, Mark I

    2014-09-01

    The sodium salt of glutamate (monosodium glutamate; MSG) imparts a savory/meaty taste to foods, and has been used as a flavoring agent for millennia. Past research on MSG/glutamate has evaluated its physiologic, metabolic and behavioral actions, and its safety. Ingested MSG has been found to be safe, and to produce no remarkable effects, except on taste. However, some recent epidemiologic and animal studies have associated MSG use with obesity and aberrations in fat metabolism. Reported effects are usually attributed to direct actions of ingested MSG in brain. As these observations conflict with past MSG research findings, a symposium was convened at the 13th International Congress on Amino Acids, Peptides and Proteins to discuss them. The principal conclusions were: (1) the proposed link between MSG intake and weight gain is likely explained by co-varying environmental factors (e.g., diet, physical activity) linked to the "nutrition transition" in developing Asian countries. (2) Controlled intervention studies adding MSG to the diet of animals and humans show no effect on body weight. (3) Hypotheses positing dietary MSG effects on body weight involve results from rodent MSG injection studies that link MSG to actions in brain not applicable to MSG ingestion studies. The fundamental reason is that glutamate is metabolically compartmentalized in the body, and generally does not passively cross biologic membranes. Hence, almost no ingested glutamate/MSG passes from gut into blood, and essentially none transits placenta from maternal to fetal circulation, or crosses the blood-brain barrier. Dietary MSG, therefore, does not gain access to brain. Overall, it appears that normal dietary MSG use is unlikely to influence energy intake, body weight or fat metabolism.

  10. Future management of human obesity: understanding the meaning of genetic susceptibility

    Directory of Open Access Journals (Sweden)

    Jenkins AB

    2014-12-01

    Full Text Available Arthur B Jenkins,1,2 Lesley V Campbell2,3 1School of Medicine, University of Wollongong, Wollongong, NSW, Australia; 2Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia; 3Diabetes Centre and Department of Endocrinology, St Vincent's Hospital, Sydney, NSW, Australia Abstract: Gene–environment interactions are central to the expression of obesity. The condition is strongly heritable (ie, genetic, and most of the variation in obesity levels between countries and between individuals can be explained by the effects of obesogenic environments on individual genetic susceptibilities. The nature of the obesogenic environmental influences is not clear in detail, but they correlate closely with measures of affluence. The causes of variation in genetic susceptibility are also not clearly defined, but their general nature has become clearer. The failure of genome-wide association studies or large linkage studies to identify or replicate causative genetic variants, together with the segregation of obesity-related traits in families, implicates a heterogenetic mechanism in which rare, dominantly or additively expressed genetic variants are responsible for most of common obesity. The search for rare causative variants continues with some successes, but those identified contribute very little to the overall burden and, assuming heterogenetics, there are many more to find. The time when genomic risk factors provide more information than do currently available markers, such as family history, is a long way off. Genomic studies to date have contributed little, if anything, to the prevention and treatment of common obesity and its associated disorders. This contrasts with the obvious and immediate potential implications of the well-established overall genetic basis of obesity, which have not yet been exploited in the clinical or public health arenas. Genomic studies, which have helped to define the genetic basis of

  11. 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.

  12. The human gut microbial ecology associated with overweight and obesity determines ellagic acid metabolism.

    Science.gov (United States)

    Selma, María V; Romo-Vaquero, María; García-Villalba, Rocío; González-Sarrías, Antonio; Tomás-Barberán, Francisco A; Espín, Juan C

    2016-04-01

    We recently identified three metabotypes (0, A and B) that depend on the metabolic profile of urolithins produced from polyphenol ellagic acid (EA). The gut microbiota and Gordonibacter spp. recently were identified as species able to produce urolithins. A higher percentage of metabotype B was found in patients with metabolic syndrome or colorectal cancer in comparison with healthy individuals. The aim of the present study was to analyse differences in EA metabolism between healthy overweight-obese and normoweight individuals and evaluate the role of gut microbial composition including Gordonibacter. Although the three metabotypes were confirmed in both groups, metabotype B prevailed in overweight-obese (31%) versus normoweight (20%) individuals while metabotype A was higher in normoweight (70%) than the overweight-obese group (57%). This suggests that weight gain favours the growth of bacteria capable of producing urolithin B and/or isourolithin A with respect to urolithin A-producing bacteria. Gordonibacter spp. levels were not significantly different between normoweight and overweight-obese groups but higher Gordonibacter levels were found in metabotype A individuals than in those with metabotype B. Other bacterial species have been reported to show a much closer relationship to obesity and dysbiosis than Gordonibacter. However, Gordonibacter levels are negatively correlated with metabotype B, which prevails in metabolic syndrome and colorectal cancer. This is the first report that links overweight and obesity with an alteration in the catabolism of EA, and where the correlation of Gordonibacter to this alteration is shown. Future investigation of Gordonibacter and urolithin metabotypes as potential biomarkers or therapeutic targets of obesity-related diseases is warranted.

  13. B Lymphocyte Stimulator (BLyS) Is Expressed in Human Adipocytes In Vivo and Is Related to Obesity but Not to Insulin Resistance

    OpenAIRE

    Nike Müller; Schulte, Dominik M.; Susann Hillebrand; Kathrin Türk; Jochen Hampe; Clemens Schafmayer; Mario Brosch; Witigo von Schönfels; Markus Ahrens; Rainald Zeuner; Schröder, Johann O.; Matthias Blüher; Christian Gutschow; Sandra Freitag-Wolf; Marta Stelmach-Mardas

    2014-01-01

    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 ...

  14. 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.

  15. 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

    receptor (MC4R), fat mass and obesity associated (FTO), neuronal growth regulator 1 (NEGR)1 and adiponectin (ADIPOQ), in seven obesity-relevant tissues (liver; muscle; pancreas; hypothalamus; and retroperitoneal, subcutaneous and mesenteric adipose tissues) in two pig breeds (production pigs and Göttingen...... 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...... shows significant differential expression in all tissues analyzed, and NEGR1 shows significant differential expression in muscle, pancreas, hypothalamus and subcutaneous adipose tissue. The MC4R transcript can be detected only in hypothalamus. In general, the expression profiles of the investigated...

  16. 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

    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...... 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....... of genes enriched in metabolic process and mitochondrial function. After weight loss, the expression of the majority of the identified genes was normalized to levels observed in normal-weight, healthy controls. Among the 14 metabolic genes analyzed, promoter methylation of 11 genes was normalized to levels...

  17. Genetic, molecular and physiological mechanisms involved in human obesity: Society for Endocrinology Medal Lecture 2012.

    Science.gov (United States)

    Farooqi, Sadaf I

    2015-01-01

    The health consequences of obesity represent one of the major public health challenges of our time. Whilst the role of environmental drivers such as reduced physical activity and increased food intake is widely acknowledged, the importance of biological factors which influence individual variation in weight is less readily recognised. Considerable evidence suggests that genetic factors influence a person's weight in a given environment and that these genetic influences are more potent at the extremes of the body mass index (BMI) distribution. The discovery that genetic disruption of certain pathways can lead to severe obesity has informed our current understanding of how body weight is regulated by brain circuits that regulate appetite and energy expenditure. These studies provide a framework for investigating patients and ultimately may guide the development of more rational-targeted therapies for genetically susceptible individuals with severe obesity.

  18. 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.

  19. Hormonal and dietary characteristics in obese human subjects with and without food addiction.

    Science.gov (United States)

    Pedram, Pardis; Sun, Guang

    2014-12-31

    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. 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, pobesity 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.

  1. Normal mitochondrial function and increased fat oxidation capacity in leg and arm muscles in obese humans

    DEFF Research Database (Denmark)

    Ara, I; Larsen, S; Stallknecht, Bente Merete

    2011-01-01

    Aim/hypothesis:The aim of this study was to investigate mitochondrial function, fibre-type distribution and substrate oxidation during exercise in arm and leg muscles in male postobese (PO), obese (O) and age- and body mass index (BMI)-matched control (C) subjects. The hypothesis of the study......, but not with differences in fibre-type composition, mitochondrial function or muscle enzyme levels compared with Cs. In PO subjects, the changes in fat oxidation are preserved during leg, but not during arm, exercise.International Journal of Obesity advance online publication, 15 June 2010; doi:10.1038/ijo.2010.123....

  2. Synchronized human skeletal myotubes of lean, obese and type 2 diabetic patients maintain circadian oscillation of clock genes

    Science.gov (United States)

    Hansen, Jan; Timmers, Silvie; Moonen-Kornips, Esther; Duez, Helene; Staels, Bart; Hesselink, Matthijs K. C.; Schrauwen, Patrick

    2016-01-01

    Cell and animal studies have demonstrated that circadian rhythm is governed by autonomous rhythmicity of clock genes. Although disturbances in circadian rhythm have been implicated in metabolic disease development, it remains unknown whether muscle circadian rhythm is altered in human models of type 2 diabetes. Here we used human primary myotubes (HPM) to investigate if rhythmicity of clock- and metabolic gene expression is altered in donors with obesity or type 2 diabetes compared to metabolically healthy donors. HPM were obtained from skeletal muscle biopsies of four groups: type 2 diabetic patients and their BMI- and age-matched obese controls and from lean, healthy and young endurance trained athletes and their age-matched sedentary controls. HPM were differentiated for 7 days before synchronization by serum shock followed by gene expression profiling over the next 72 hours. HPM display robust circadian rhythms in clock genes, but REVERBA displayed dampened rhythmicity in type 2 diabetes. Furthermore, rhythmicity in NAMPT and SIRT1 expression was only observed in HPM from trained athletes. Rhythmicity in expression of key-regulators of carbohydrate and lipid metabolism was modest. We demonstrate that in human skeletal muscle REVERBA/B, NAMPT and SIRT1 circadian rhythms are affected in donors of sedentary life style and poor health status. PMID:27756900

  3. 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.

  4. Functional consequences of microbial shifts in the human gastrointestinal tract linked to antibiotic treatment and obesity

    NARCIS (Netherlands)

    Hernandez, E.; Bargiela, R.; Suarez Diez, M.; Friedrichs, A.; Pérez-Cobas, A.E.; Gosalbes, M.J.; Knecht, H.; Martinez-Martinez, M.; Seifert, J.; Bergen, von M.; Martins Dos Santos, V.A.P.

    2013-01-01

    The microbiomes in the gastrointestinal tract (GIT) of individuals receiving antibiotics and those in obese subjects undergo compositional shifts, the metabolic effects and linkages of which are not clearly understood. Herein, we set to gain insight into these effects, particularly with regard to ca

  5. 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...

  6. Increasing dietary fat elicits similar changes in fat oxidation and markers of muscle oxidative capacity in lean and obese humans.

    Directory of Open Access Journals (Sweden)

    Audrey Bergouignan

    Full Text Available In lean humans, increasing dietary fat intake causes an increase in whole-body fat oxidation and changes in genes that regulate fat oxidation in skeletal muscle, but whether this occurs in obese humans is not known. We compared changes in whole-body fat oxidation and markers of muscle oxidative capacity differ in lean (LN and obese (OB adults exposed to a 2-day high-fat (HF diet. Ten LN (BMI = 22.5±2.5 kg/m², age = 30±8 yrs and nine OB (BMI = 35.9±4.93 kg/m², 38±5 yrs, Mean±SD were studied in a room calorimeter for 24hr while consuming isocaloric low-fat (LF, 20% of energy and HF (50% of energy diets. A muscle biopsy was obtained the next morning following an overnight fast. 24h respiratory quotient (RQ did not significantly differ between groups (LN: 0.91±0.01; OB: 0.92±0.01 during LF, and similarly decreased during HF in LN (0.86±0.01 and OB (0.85±0.01. The expression of pyruvate dehydrogenase kinase 4 (PDK4 and the fatty acid transporter CD36 increased in both LN and OB during HF. No other changes in mRNA or protein were observed. However, in both LN and OB, the amounts of acetylated peroxisome proliferator-activated receptor γ coactivator-1-α (PGC1-α significantly decreased and phosphorylated 5-AMP-activated protein kinase (AMPK significantly increased. In response to an isoenergetic increase in dietary fat, whole-body fat oxidation similarly increases in LN and OB, in association with a shift towards oxidative metabolism in skeletal muscle, suggesting that the ability to adapt to an acute increase in dietary fat is not impaired in obesity.

  7. CCAAT-enhancer-binding protein β (C/EBPβ) and downstream human placental growth hormone genes are targets for dysregulation in pregnancies complicated by maternal obesity.

    Science.gov (United States)

    Vakili, Hana; Jin, Yan; Menticoglou, Savas; Cattini, Peter A

    2013-08-01

    Human chorionic somatomammotropin (CS) and placental growth hormone variant (GH-V) act as metabolic adaptors in response to maternal insulin resistance, which occurs in "normal" pregnancy. Maternal obesity can exacerbate this "resistance," suggesting that CS, GH-V, or transcription factors that regulate their production might be targets. The human CS genes, hCS-A and hCS-B, flank the GH-V gene. A significant decrease in pre-term placental CS/GH-V RNA levels was observed in transgenic mice containing the CS/GH-V genes in a model of high fat diet (HFD)-induced maternal obesity. Similarly, a decrease in CS/GH-V RNA levels was detected in term placentas from obese (body mass index (BMI) ≥ 35 kg/m(2)) versus lean (BMI 20-25 kg/m(2)) women. A specific decrease in transcription factor CCAAT-enhancer-binding protein β (C/EBPβ) RNA levels was also seen with obesity; C/EBPβ is required for mouse placenta development and is expressed, like CS and GH-V, in syncytiotrophoblasts. Binding of C/EBPβ to the CS gene downstream enhancer regions, which by virtue of their position distally flank the GH-V gene, was reduced in placenta chromatin from mice on a HFD and in obese women; a corresponding decrease in RNA polymerase II associated with CS/GH-V promoters was also observed. Detection of decreased endogenous CS/GH-V RNA levels in human placental tumor cells treated with C/EBPβ siRNA is consistent with a direct effect. These data provide evidence for CS/GH-V dysregulation in acute HFD-induced obesity in mouse pregnancy and chronic obesity in human pregnancy and implicate C/EBPβ, a factor associated with CS regulation and placental development.

  8. CCAAT-enhancer-binding Protein β (C/EBPβ) and Downstream Human Placental Growth Hormone Genes Are Targets for Dysregulation in Pregnancies Complicated by Maternal Obesity*

    Science.gov (United States)

    Vakili, Hana; Jin, Yan; Menticoglou, Savas; Cattini, Peter A.

    2013-01-01

    Human chorionic somatomammotropin (CS) and placental growth hormone variant (GH-V) act as metabolic adaptors in response to maternal insulin resistance, which occurs in “normal” pregnancy. Maternal obesity can exacerbate this “resistance,” suggesting that CS, GH-V, or transcription factors that regulate their production might be targets. The human CS genes, hCS-A and hCS-B, flank the GH-V gene. A significant decrease in pre-term placental CS/GH-V RNA levels was observed in transgenic mice containing the CS/GH-V genes in a model of high fat diet (HFD)-induced maternal obesity. Similarly, a decrease in CS/GH-V RNA levels was detected in term placentas from obese (body mass index (BMI) ≥ 35 kg/m2) versus lean (BMI 20–25 kg/m2) women. A specific decrease in transcription factor CCAAT-enhancer-binding protein β (C/EBPβ) RNA levels was also seen with obesity; C/EBPβ is required for mouse placenta development and is expressed, like CS and GH-V, in syncytiotrophoblasts. Binding of C/EBPβ to the CS gene downstream enhancer regions, which by virtue of their position distally flank the GH-V gene, was reduced in placenta chromatin from mice on a HFD and in obese women; a corresponding decrease in RNA polymerase II associated with CS/GH-V promoters was also observed. Detection of decreased endogenous CS/GH-V RNA levels in human placental tumor cells treated with C/EBPβ siRNA is consistent with a direct effect. These data provide evidence for CS/GH-V dysregulation in acute HFD-induced obesity in mouse pregnancy and chronic obesity in human pregnancy and implicate C/EBPβ, a factor associated with CS regulation and placental development. PMID:23782703

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

    Science.gov (United States)

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

    2013-07-01

    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 wide association studies) for obesity and T2D in human adipocytes. The mRNA expression of lipid and glucose metabolism genes was changed upon the treatment of human primary adipocytes with SPIONs. mRNA of GULP1, SLC30A8, NEGR1, SEC16B, MTCH2, MAF, MC4R, and TMEM195 were severely induced, whereas INSIG2, NAMPT, MTMR9, PFKP, KCTD15, LPL and GNPDA2 were down-regulated upon SPIONs stimulation. Since SEC16B gene assist the phagocytosis of apoptotic cells and this gene were highly expressed upon SPIONs treatment in adipocytes, it is logic to assume that SPIONs may play a crucial role in this direction, which requires more consideration in the future.

  10. 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 BACKGROUND: 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. METHODOLOGY: 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. PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: Obesity is associated with elevated serum levels of pro-inflammatory wnt5a in humans. Furthermore, caloric restriction beneficially affects serum concentrations

  11. 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.

  12. Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals.

    Directory of Open Access Journals (Sweden)

    Anja Böhm

    Full Text Available Among obese subjects, metabolically healthy and unhealthy obesity (MHO/MUHO can be differentiated: the latter is characterized by whole-body insulin resistance, hepatic steatosis, and subclinical inflammation. Aim of this study was, to identify adipocyte-specific metabolic signatures and functional biomarkers for MHO versus MUHO.10 insulin-resistant (IR vs. 10 insulin-sensitive (IS non-diabetic morbidly obese (BMI >40 kg/m2 Caucasians were matched for gender, age, BMI, and percentage of body fat. From subcutaneous fat biopsies, primary preadipocytes were isolated and differentiated to adipocytes in vitro. About 280 metabolites were investigated by a targeted metabolomic approach intracellularly, extracellularly, and in plasma.Among others, aspartate was reduced intracellularly to one third (p = 0.0039 in IR adipocytes, pointing to a relative depletion of citric acid cycle metabolites or reduced aspartate uptake in MUHO. Other amino acids, already known to correlate with diabetes and/or obesity, were identified to differ between MUHO's and MHO's adipocytes, namely glutamine, histidine, and spermidine. Most species of phosphatidylcholines (PCs were lower in MUHO's extracellular milieu, though simultaneously elevated intracellularly, e.g., PC aa C32∶3, pointing to increased PC synthesis and/or reduced PC release. Furthermore, altered arachidonic acid (AA metabolism was found: 15(S-HETE (15-hydroxy-eicosatetraenoic acid; 0 vs. 120pM; p = 0.0014, AA (1.5-fold; p = 0.0055 and docosahexaenoic acid (DHA, C22∶6; 2-fold; p = 0.0033 were higher in MUHO. This emphasizes a direct contribution of adipocytes to local adipose tissue inflammation. Elevated DHA, as an inhibitor of prostaglandin synthesis, might be a hint for counter-regulatory mechanisms in MUHO.We identified adipocyte-inherent metabolic alterations discriminating between MHO and MUHO.

  13. Functional consequences of microbial shifts in the human gastrointestinal tract linked to antibiotic treatment and obesity.

    Science.gov (United States)

    Hernández, Ester; Bargiela, Rafael; Diez, María Suárez; Friedrichs, Anette; Pérez-Cobas, Ana Elena; Gosalbes, María José; Knecht, Henrik; Martínez-Martínez, Mónica; Seifert, Jana; von Bergen, Martin; Artacho, Alejandro; Ruiz, Alicia; Campoy, Cristina; Latorre, Amparo; Ott, Stephan J; Moya, Andrés; Suárez, Antonio; Martins dos Santos, Vitor A P; Ferrer, Manuel

    2013-01-01

    The microbiomes in the gastrointestinal tract (GIT) of individuals receiving antibiotics and those in obese subjects undergo compositional shifts, the metabolic effects and linkages of which are not clearly understood. Herein, we set to gain insight into these effects, particularly with regard to carbohydrate metabolism, and to contribute to unravel the underlying mechanisms and consequences for health conditions. We measured the activity level of GIT carbohydrate-active enzymes toward 23 distinct sugars in adults patients (n = 2) receiving 14-d β-lactam therapy and in obese (n = 7) and lean (n = 5) adolescents. We observed that both 14 d antibiotic-treated and obese subjects showed higher and less balanced sugar anabolic capacities, with 40% carbohydrates being preferentially processed as compared with non-treated and lean patients. Metaproteome-wide metabolic reconstructions confirmed that the impaired utilization of sugars propagated throughout the pentose phosphate metabolism, which had adverse consequences for the metabolic status of the GIT microbiota. The results point to an age-independent positive association between GIT glycosidase activity and the body mass index, fasting blood glucose and insulin resistance (r ( 2) ≥ 0.95). Moreover, antibiotics altered the active fraction of enzymes controlling the thickness, composition and consistency of the mucin glycans. Our data and analyses provide biochemical insights into the effects of antibiotic usage on the dynamics of the GIT microbiota and pin-point presumptive links to obesity. The knowledge and the hypotheses generated herein lay a foundation for subsequent, systematic research that will be paramount for the design of "smart" dietary and therapeutic interventions to modulate host-microbe metabolic co-regulation in intestinal homeostasis.

  14. Interleukin-7 Plasma Levels in Human Differentiate Anorexia Nervosa, Constitutional Thinness and Healthy Obesity

    Science.gov (United States)

    Germain, Natacha; Viltart, Odile; Loyens, Anne; Bruchet, Céline; Nadin, Katia; Wolowczuk, Isabelle; Estour, Bruno; Galusca, Bogdan

    2016-01-01

    Introduction Interleukin-7 (IL-7) is a cytokine involved in energy homeostasis as demonstrated in rodents. Anorexia nervosa is characterized by restrained eating behavior despite adaptive orexigenic regulation profile including high ghrelin plasma levels. Constitutional thinness is a physiological condition of resistance to weight gain with physiological anorexigenic profile including high Peptide YY plasma level. Healthy obesity can be considered as a physiological state of resistance to weight loss with opposite appetite regulating profile to constitutional thinness including low Peptide YY plasma level. No studies in IL-7 are yet available in those populations. Therefore we evaluated circadian plasma levels of IL-7 in anorexia nervosa compared to constitutional thinness, healthy obese and control females. Materials and Methods 10 restrictive-type anorexia nervosa women, 5 bingeing/purging anorexia nervosa woman, 5 recovered restrictive anorexia nervosa women, 4 bulimic females, 10 constitutional thinness women, 7 healthy obese females, and 10 normal weight women controls were enrolled in this cross-sectional study, performed in endocrinology unit and academic laboratory. Twelve-point circadian profiles of plasma IL-7 levels were measured in each subject. Results 24h mean IL-7 plasma levels (pg/ml, mean±SEM) were decreased in restrictive-type anorexia nervosa (123.4±14.4, pobese patients (51±3.2, pobesity, with low IL-7, is once again in mirror image of constitutional thinness with normal high IL-7. PMID:27611669

  15. 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.

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

    Science.gov (United States)

    Müller, Nike; Schulte, Dominik M; Hillebrand, Susann; Türk, Kathrin; Hampe, Jochen; Schafmayer, Clemens; Brosch, Mario; von Schönfels, Witigo; Ahrens, Markus; Zeuner, Rainald; Schröder, Johann O; Blüher, Matthias; Gutschow, Christian; Freitag-Wolf, Sandra; Stelmach-Mardas, Marta; Saggau, Carina; Schreiber, Stefan; Laudes, Matthias

    2014-01-01

    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 (pr = 0.43, panti-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.

  17. Lipid exposure elicits differential responses in gene expression and DNA methylation in primary human skeletal muscle cells from severely obese women.

    Science.gov (United States)

    Maples, Jill M; Brault, Jeffrey J; Shewchuk, Brian M; Witczak, Carol A; Zou, Kai; Rowland, Naomi; Hubal, Monica J; Weber, Todd M; Houmard, Joseph A

    2015-05-01

    The skeletal muscle of obese individuals exhibits an impaired ability to increase the expression of genes linked with fatty acid oxidation (FAO) upon lipid exposure. The present study determined if this response could be attributed to differential DNA methylation signatures. RNA and DNA were isolated from primary human skeletal muscle cells (HSkMC) from lean and severely obese women following lipid incubation. mRNA expression and DNA methylation were quantified for genes that globally regulate FAO [PPARγ coactivator (PGC-1α), peroxisome proliferator-activated receptors (PPARs), nuclear respiratory factors (NRFs)]. With lipid oversupply, increases in NRF-1, NRF-2, PPARα, and PPARδ expression were dampened in skeletal muscle from severely obese compared with lean women. The expression of genes downstream of the PPARs and NRFs also exhibited a pattern of not increasing as robustly upon lipid exposure with obesity. Increases in CpG methylation near the transcription start site with lipid oversupply were positively related to PPARδ expression; increases in methylation with lipid were depressed in HSkMC from severely obese women. With severe obesity, there is an impaired ability to upregulate global transcriptional regulators of FAO in response to lipid exposure. Transient changes in DNA methylation patterns and differences in the methylation signature with severe obesity may play a role in the transcriptional regulation of PPARδ in response to lipid. The persistence of differential responses to lipid in HSkMC derived from lean and obese subjects supports the possibility of stable epigenetic programming of skeletal muscle cells by the respective environments.

  18. Pediatric Obesity: Etiology and Treatment^

    OpenAIRE

    Crocker, Melissa K.; Yanovski, Jack A.

    2011-01-01

    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...

  19. 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

    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......2 pig design, by estimating heritabilities, genetic and phenotypic correlations using mixed- and multi-trait BLUP animal models. Our analyses revealed high coefficients of variation (15-42 per cent) and moderate to high heritabilities (0.22 - 0.81) in fatness traits, showing large phenotypic...

  20. No genetic footprints of the fat mass and obesity associated (FTO) gene in human plasma 1H CPMG NMR metabolic profiles

    DEFF Research Database (Denmark)

    Kjeldahl, Karin; Rasmussen, Morten Arendt; Hasselbalch, Ann Louise

    2014-01-01

    In this paper it was investigated if any genotypic footprints from the fat mass and obesity associated (FTO) SNP could be found in 600 MHz 1H CPMG NMR profiles of around 1,000 human plasma samples from healthy Danish twins. The problem was addressed with a combination of univariate and multivariate...

  1. Anatomical locations of human brown adipose tissue: functional relevance and implications in obesity and type 2 diabetes.

    Science.gov (United States)

    Sacks, Harold; Symonds, Michael E

    2013-06-01

    We will review information about and present hypotheses as to the anatomy of brown adipose tissue (BAT). Why is it located where it is in humans? Its anatomical distribution is likely to confer survival value by protecting critical organs from hypothermia by adaptive thermogenesis. Ultimately, the location and function will be important when considering therapeutic strategies for preventing and treating obesity and type 2 diabetes, in which case successful interventions will need to have a significant effect on BAT function in subjects living in a thermoneutral environment. In view of the diverse locations and potential differences in responsiveness between BAT depots, it is likely that BAT will be shown to have much more subtle and thus previously overlooked functions and regulatory control mechanisms.

  2. TLR-3 is present in human adipocytes, but its signalling is not required for obesity-induced inflammation in adipose tissue in vivo.

    Directory of Open Access Journals (Sweden)

    Dov B Ballak

    Full Text Available Innate immunity plays a pivotal role in obesity-induced low-grade inflammation originating from adipose tissue. Key receptors of the innate immune system including Toll-like receptors-2 and -4 (TLRs are triggered by nutrient excess to promote inflammation. The role of other TLRs in this process is largely unknown. In addition to double-stranded viral mRNA, TLR-3 can also recognize mRNA from dying endogenous cells, a process that is frequently observed within obese adipose tissue. Here, we identified profound expression of TLR-3 in adipocytes and investigated its role during diet-induced obesity. Human adipose tissue biopsies (n=80 and an adipocyte cell-line were used to study TLR-3 expression and function. TLR-3-/- and WT animals were exposed to a high-fat diet (HFD for 16 weeks to induce obesity. Expression of TLR-3 was significantly higher in human adipocytes compared to the non-adipocyte cells part of the adipose tissue. In vitro, TLR-3 expression was induced during differentiation of adipocytes and stimulation of the receptor led to elevated expression of pro-inflammatory cytokines. In vivo, TLR-3 deficiency did not significantly influence HFD-induced obesity, insulin sensitivity or inflammation. In humans, TLR-3 expression in adipose tissue did not correlate with BMI or insulin sensitivity (HOMA-IR. Together, our results demonstrate that TLR-3 is highly expressed in adipocytes and functionally active. However, TLR-3 appears to play a redundant role in obesity-induced inflammation and insulin resistance.

  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

    chemoattractant protein-1 (MCP-1), IL-6 (interleukin-6) and adiponectin). CONCLUSION: FA1 serum levels were increased in obese subjects and might influence S(i). The stimulatory effect of FA1 protein on pro-inflammatory cytokines on both immune and adipose cell types could contribute to worsening the inflammatory...... 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. 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

    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...... 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...... directions for research. In previous studies, gene expression analyses show a coordinated pattern of reduction in nuclear-encoded mitochondrial gene expression in insulin resistance. However, changes in mRNA levels may not predict changes in protein abundance. An approach to identify global protein abundance...

  5. Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity.

    Science.gov (United States)

    Lackey, Denise E; Lynch, Christopher J; Olson, Kristine C; Mostaedi, Rouzbeh; Ali, Mohamed; Smith, William H; Karpe, Fredrik; Humphreys, Sandy; Bedinger, Daniel H; Dunn, Tamara N; Thomas, Anthony P; Oort, Pieter J; Kieffer, Dorothy A; Amin, Rajesh; Bettaieb, Ahmed; Haj, Fawaz G; Permana, Paska; Anthony, Tracy G; Adams, Sean H

    2013-06-01

    Elevated blood branched-chain amino acids (BCAA) are often associated with insulin resistance and type 2 diabetes, which might result from a reduced cellular utilization and/or incomplete BCAA oxidation. White adipose tissue (WAT) has become appreciated as a potential player in whole body BCAA metabolism. We tested if expression of the mitochondrial BCAA oxidation checkpoint, branched-chain α-ketoacid dehydrogenase (BCKD) complex, is reduced in obese WAT and regulated by metabolic signals. WAT BCKD protein (E1α subunit) was significantly reduced by 35-50% in various obesity models (fa/fa rats, db/db mice, diet-induced obese mice), and BCKD component transcripts significantly lower in subcutaneous (SC) adipocytes from obese vs. lean Pima Indians. Treatment of 3T3-L1 adipocytes or mice with peroxisome proliferator-activated receptor-γ agonists increased WAT BCAA catabolism enzyme mRNAs, whereas the nonmetabolizable glucose analog 2-deoxy-d-glucose had the opposite effect. The results support the hypothesis that suboptimal insulin action and/or perturbed metabolic signals in WAT, as would be seen with insulin resistance/type 2 diabetes, could impair WAT BCAA utilization. However, cross-tissue flux studies comparing lean vs. insulin-sensitive or insulin-resistant obese subjects revealed an unexpected negligible uptake of BCAA from human abdominal SC WAT. This suggests that SC WAT may not be an important contributor to blood BCAA phenotypes associated with insulin resistance in the overnight-fasted state. mRNA abundances for BCAA catabolic enzymes were markedly reduced in omental (but not SC) WAT of obese persons with metabolic syndrome compared with weight-matched healthy obese subjects, raising the possibility that visceral WAT contributes to the BCAA metabolic phenotype of metabolically compromised individuals.

  6. Cathepsin-D, a key protease in breast cancer, is up-regulated in obese mouse and human adipose tissue, and controls adipogenesis.

    Directory of Open Access Journals (Sweden)

    Olivier Masson

    Full Text Available The aspartic protease cathepsin-D (cath-D is overexpressed by human epithelial breast cancer cells and is closely correlated with poor prognosis in breast cancer. The adipocyte is one of the most prominent cell types in the tumor-microenvironment of breast cancer, and clinical studies have shown that obesity increases the incidence of breast cancer. Here, we provide the first evidence that cath-D expression is up-regulated in adipose tissue from obese human beings, as well as in adipocytes from the obese C57BI6/J mouse. Cath-D expression is also increased during human and mouse adipocyte differentiation. We show that cath-D silencing in 3T3-F442A murine preadipocytes leads to lipid-depleted cells after adipogenesis induction, and inhibits of the expression of PPARγ, HSL and aP2 adipocyte differentiation markers. Altogether, our findings demonstrate the key role of cath-D in the control of adipogenesis, and suggest that cath-D may be a novel target in obesity.

  7. 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.

  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

    2017-01-01

    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, adipose stores and metabolic effects from human studies, including studies amongst normal weight subjects and relevant animal experimentation. Six small short term (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. PMID:28106818

  9. 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.

  10. 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.

  11. Identification of direct and indirect social network effects in the pathophysiology of insulin resistance in obese human subjects.

    Directory of Open Access Journals (Sweden)

    Christian H C A Henning

    Full Text Available OBJECTIVE: The aim of the present study was to examine to what extent different social network mechanisms are involved in the pathogenesis of obesity and insulin-resistance. DESIGN: We used nonparametric and parametric regression models to analyse whether individual BMI and HOMA-IR are determined by social network characteristics. SUBJECTS AND METHODS: A total of 677 probands (EGO and 3033 social network partners (ALTER were included in the study. Data gathered from the probands include anthropometric measures, HOMA-IR index, health attitudes, behavioural and socio-economic variables and social network data. RESULTS: We found significant treatment effects for ALTERs frequent dieting (p<0.001 and ALTERs health oriented nutritional attitudes (p<0.001 on EGO's BMI, establishing a significant indirect network effect also on EGO's insulin resistance. Most importantly, we also found significant direct social network effects on EGO's insulin resistance, evidenced by an effect of ALTERs frequent dieting (p = 0.033 and ALTERs sport activities (p = 0.041 to decrease EGO's HOMA-IR index independently of EGO's BMI. CONCLUSIONS: Social network phenomena appear not only to be relevant for the spread of obesity, but also for the spread of insulin resistance as the basis for type 2 diabetes. Attitudes and behaviour of peer groups influence EGO's health status not only via social mechanisms, but also via socio-biological mechanisms, i.e. higher brain areas might be influenced not only by biological signals from the own organism, but also by behaviour and knowledge from different human individuals. Our approach allows the identification of peer group influence controlling for potential homophily even when using cross-sectional observational data.

  12. 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

  13. Impact of metabolic regulators on the expression of the obesity associated genes FTO and NAMPT in human preadipocytes and adipocytes.

    Directory of Open Access Journals (Sweden)

    Daniela Friebe

    Full Text Available BACKGROUND: FTO and NAMPT/PBEF/visfatin are thought to play a role in obesity but their transcriptional regulation in adipocytes is not fully understood. In this study, we evaluated the transcriptional regulation of FTO and NAMPT in preadipocytes and adipocytes by metabolic regulators. METHODOLOGY AND PRINCIPAL FINDINGS: We assessed FTO mRNA expression during human adipocyte differentiation of Simpson-Golabi-Behmel syndrome (SGBS cells and primary subcutaneous preadipocytes in vitro and evaluated the effect of the metabolic regulators glucose, insulin, dexamethasone, IGF-1 and isoproterenol on FTO and NAMPT mRNA expression in SGBS preadipocytes and adipocytes. FTO mRNA levels were not significantly modulated during adipocyte differentiation. Also, metabolic regulators had no impact on FTO expression in preadipocytes or adipocytes. In SGBS preadipocytes NAMPT expression was more than 3fold induced by dexamethasone and isoproterenol and 1.6fold by dexamethasone in adipocytes. Complete glucose restriction caused an increase in NAMPT mRNA expression by more than 5fold and 1.4fold in SGBS preadipocytes and adipocytes, respectively. CONCLUSION: FTO mRNA expression is not significantly affected by differentiation or metabolic regulators in human adipocytes. The stimulation of NAMPT expression by dexamethasone, isoproterenol and complete glucose restriction may indicate a regulation of NAMPT by metabolic stress, which was more pronounced in preadipocytes compared to mature adipocytes.

  14. Impact of Metabolic Regulators on the Expression of the Obesity Associated Genes FTO and NAMPT in Human Preadipocytes and Adipocytes

    Science.gov (United States)

    Schönberg, Maria; Bernhard, Falk; Büttner, Petra; Landgraf, Kathrin; Kiess, Wieland; Körner, Antje

    2011-01-01

    Background FTO and NAMPT/PBEF/visfatin are thought to play a role in obesity but their transcriptional regulation in adipocytes is not fully understood. In this study, we evaluated the transcriptional regulation of FTO and NAMPT in preadipocytes and adipocytes by metabolic regulators. Methodology and Principal Findings We assessed FTO mRNA expression during human adipocyte differentiation of Simpson-Golabi-Behmel syndrome (SGBS) cells and primary subcutaneous preadipocytes in vitro and evaluated the effect of the metabolic regulators glucose, insulin, dexamethasone, IGF-1 and isoproterenol on FTO and NAMPT mRNA expression in SGBS preadipocytes and adipocytes. FTO mRNA levels were not significantly modulated during adipocyte differentiation. Also, metabolic regulators had no impact on FTO expression in preadipocytes or adipocytes. In SGBS preadipocytes NAMPT expression was more than 3fold induced by dexamethasone and isoproterenol and 1.6fold by dexamethasone in adipocytes. Complete glucose restriction caused an increase in NAMPT mRNA expression by more than 5fold and 1.4fold in SGBS preadipocytes and adipocytes, respectively. Conclusion FTO mRNA expression is not significantly affected by differentiation or metabolic regulators in human adipocytes. The stimulation of NAMPT expression by dexamethasone, isoproterenol and complete glucose restriction may indicate a regulation of NAMPT by metabolic stress, which was more pronounced in preadipocytes compared to mature adipocytes. PMID:21687707

  15. Prandial subcutaneous injections of glucagon-like peptide-1 cause weight loss in obese human subjects

    DEFF Research Database (Denmark)

    Näslund, Erik; King, N; Mansten, S;

    2004-01-01

    Recombinant glucagon-like peptide-1 (7-36)amide (rGLP-1) was recently shown to cause significant weight loss in type 2 diabetics when administered for 6 weeks as a continuous subcutaneous infusion. The mechanisms responsible for the weight loss are not clarified. In the present study, rGLP-1...... was given for 5 d by prandial subcutaneous injections (PSI) (76 nmol 30 min before meals, four times daily; a total of 302.4 nmol/24 h) or by continuous subcutaneous infusion (CSI) (12.7 nmol/h; a total of 304.8 nmol/24 h). This was performed in nineteen healthy obese subjects (mean age 44.2 (sem 2.5) years......; BMI 39.0 (sem 1.2) kg/m(2)) in a prospective randomised, double-blind, placebo-controlled, cross-over study. Compared with the placebo, rGLP-1 administered as PSI and by CSI generated a 15 % reduction in mean food intake per meal (P=0.02) after 5 d treatment. A weight loss of 0.55 (sem 0.2) kg (P

  16. Jejunal administration of glucose enhances acyl ghrelin suppression in obese humans.

    Science.gov (United States)

    Tamboli, Robyn A; Sidani, Reem M; Garcia, Anna E; Antoun, Joseph; Isbell, James M; Albaugh, Vance L; Abumrad, Naji N

    2016-07-01

    Ghrelin is a gastric hormone that stimulates hunger and worsens glucose metabolism. Circulating ghrelin is decreased after Roux-en-Y gastric bypass (RYGB) surgery; however, the mechanism(s) underlying this change is unknown. We tested the hypothesis that jejunal nutrient exposure plays a significant role in ghrelin suppression after RYGB. Feeding tubes were placed in the stomach or jejunum in 13 obese subjects to simulate pre-RYGB or post-RYGB glucose exposure to the gastrointestinal (GI) tract, respectively, without the confounding effects of caloric restriction, weight loss, and surgical stress. On separate study days, the plasma glucose curves obtained with either gastric or jejunal administration of glucose were replicated with intravenous (iv) infusions of glucose. These "isoglycemic clamps" enabled us to determine the contribution of the GI tract and postabsorptive plasma glucose to acyl ghrelin suppression. Plasma acyl ghrelin levels were suppressed to a greater degree with jejunal glucose administration compared with gastric glucose administration (P 0.05). Direct exposure of the proximal jejunum to glucose increases acyl ghrelin suppression independent of circulating glucose levels. The enhanced suppression of acyl ghrelin after RYGB may be due to a nutrient-initiated signal in the jejunum that regulates ghrelin secretion.

  17. Establishment of a human flora associated mice for obesity patient%肥胖患者HFA小鼠模型的建立

    Institute of Scientific and Technical Information of China (English)

    曾本华; 唐欢; 李文霞; 袁静; 邓人伟; 魏泓

    2012-01-01

    Objective To study gut microbiota of obesity patient colonized in germ free mice. Method 20 Kunming mice were inoculated with feces from an obesity patient to construct a human flora associated ( HFA) mice model. Feces of HFA mice and patient were detected by denaturing gradient gel electrophoresis. Result The richness (S) of obesity patient and HFA mice were 24 and 12.04 ± 3.68; ihe Shannon Index (H') of obesity patient and HFA mice were 3. 02 and 2. 46 ± 0. 33; the Similarity Dice of obesity patient and HFA mice was 26%. Most gut microbiota of male mice differed from those of female mice in the cluster profile; and the gut microbiota of male HFA mice were more semblable to human donor than those of female mice. Conclusion HFA mice are able to partly imitate microbiota of obesity patient. The HFA mice model for obesity patient is a new tool for study of the relationship between obesity and microbiota.%目的 研究肥胖患者的肠道菌群在无菌小鼠体内的定植规律.方法 选取20只无菌KM小鼠,接种肥胖患者的粪便,构建菌群人源化(HFA)动物模型,利用变性梯度凝胶电泳技术(DGGE)评价患者肠道菌群在无菌小鼠体内的定植规律.结果 HFA小鼠菌群平均丰富度(richness,S)为12.04±3.68,肥胖患者的条带S为24,为HFA小鼠S的2倍;肥胖患者Shannon指数(H')为3.02,HFA小鼠平均H'为2.46±0.33;HFA小鼠与人肠道菌群的总相似度为26%;大部分雌性HFA小鼠与雄性HFA小鼠在聚类分析图上分离,且雄性HFA小鼠与患者更为相似.结论 HFA小鼠体内能部分模拟肥胖患者的微生物区系,且与患者性别相同的小鼠模拟得更好.本实验建立的HFA模型为肥胖与肠道菌群关系的进一步研究提供新的选择.

  18. Epigenetics of Obesity.

    Science.gov (United States)

    Lopomo, A; Burgio, E; Migliore, L

    2016-01-01

    Obesity is a metabolic disease, which is becoming an epidemic health problem: it has been recently defined in terms of Global Pandemic. Over the years, the approaches through family, twins and adoption studies led to the identification of some causal genes in monogenic forms of obesity but the origins of the pandemic of obesity cannot be considered essentially due to genetic factors, because human genome is not likely to change in just a few years. Epigenetic studies have offered in recent years valuable tools for the understanding of the worldwide spread of the pandemic of obesity. The involvement of epigenetic modifications-DNA methylation, histone tails, and miRNAs modifications-in the development of obesity is more and more evident. In the epigenetic literature, there are evidences that the entire embryo-fetal and perinatal period of development plays a key role in the programming of all human organs and tissues. Therefore, the molecular mechanisms involved in the epigenetic programming require a new and general pathogenic paradigm, the Developmental Origins of Health and Disease theory, to explain the current epidemiological transition, that is, the worldwide increase of chronic, degenerative, and inflammatory diseases such as obesity, diabetes, cardiovascular diseases, neurodegenerative diseases, and cancer. Obesity and its related complications are more and more associated with environmental pollutants (obesogens), gut microbiota modifications and unbalanced food intake, which can induce, through epigenetic mechanisms, weight gain, and altered metabolic consequences.

  19. CD36- and GPR120-mediated Ca2+ Signaling in Human Taste Bud Cells Mediates Differential Responses to Fatty Acids and is Altered in Obese Mice

    Science.gov (United States)

    Ozdener, Mehmet Hakan; Subramaniam, Selvakumar; Sundaresan, Sinju; Sery, Omar; Hashimoto, Toshihiro; Asakawa, Yoshinori; Besnard, Philippe; Abumrad, Nada A.; Khan, Naim Akhtar

    2014-01-01

    Background & Aims It is important to increase our understanding of gustatory detection of dietary fat and its contribution to fat preference. We studied the roles of the fat taste receptors CD36 and GPR120 and their interactions via Ca2+ signaling in fungiform taste bud cells (TBC). Methods We measured Ca2+ signaling in human TBC, transfected with small interfering RNAs (siRNAs) against mRNAs encoding CD36 and GPR120 (or control siRNAs). We also studied Ca2+ signaling in TBC from CD36−/− mice and from wild-type lean and obese mice. Additional studies were conducted with mouse enteroendocrine cell line STC-1 that express GPR120 and stably transfected with human CD36. We measured release of serotonin and GLP-1 from human and mice TBC in response to CD36 and GPR120 activation. Results High concentrations of linoleic acid induced Ca2+ signaling via CD36 and GPR120 in human and mice TBC as well as in STC-1 cells, whereas low concentrations induced Ca2+ signaling via only CD36. Incubation of human and mice fungiform TBC with lineoleic acid downregulated CD36 and upregulated GPR120 in membrane lipid rafts. Obese mice had decreased spontaneous preference for fat. Fungiform TBC from obese mice had reduced Ca2+ and serotonin responses but increased release of GLP1, along with reduced levels of CD36 and increased levels of GPR120 in lipid rafts. Conclusions CD36 and GPR120 have non-overlapping roles in TBC signaling during oro-gustatory perception of dietary lipids; these are differentially regulated by obesity. PMID:24412488

  20. “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

  1. 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 crossov

  2. 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.

  3. Childhood Asthma May Encourage Obesity, Study Suggests

    Science.gov (United States)

    ... Human Services. More Health News on: Asthma in Children Obesity in Children Recent Health News Related MedlinePlus Health Topics Asthma in Children Obesity in Children About MedlinePlus Site Map FAQs Customer ...

  4. Genetics of obesity.

    Science.gov (United States)

    Clement, Karine; Boutin, Philippe; Froguel, Philippe

    2002-01-01

    Obesity is a typical common multifactorial disease in which environmental and genetic factors interact. In rare cases of severe obesity with childhood onset, a single gene has a major effect in determining the occurrence of obesity, with the environment having only a permissive role in the severity of the phenotype. Exceptional mutations of the leptin gene and its receptor, pro-opiomelanocortine (POMC), prohormone convertase 1 (PC1) and more frequently, mutations in the melanocortin receptor 4 (1 to 4% of very obese cases) have been described. All these obesity genes encode proteins that are strongly connected as part of the same loop of the regulation of food intake. They all involve the leptin axis and one of its hypothalamic targets; the melanocortin pathway. Pathways of bodyweight regulation involved in monogenic forms of obesity might represent targets for future drug development. Successful leptin protein replacement in a leptin-deficient child has contributed to the validation of the usefulness of gene screening in humans. However, the individual variability in response to leptin treatment might be related to genetic variability. The efficiency of leptin itself or of small-molecule agonists of the leptin receptor should be studied in relation with genetic variations in the leptin gene promoter. The most common forms of obesity are polygenic. Two general approaches have been used to date in the search for genes underlying common polygenic obesity in humans. The first approach focuses on selected genes having some plausible role in obesity on the basis of their known or presumed biological role. This approach yielded putative susceptibility genes with only small or uncertain effects. The second approach attempts to map genes purely by position and requires no presumptions on the function of genes. Genome-wide scans identify chromosomal regions showing linkage with obesity in large collections of nuclear families. Genome-wide scans in different ethnic

  5. 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 INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Human subcutaneous WAT cells can be induced to attain BAT characteristics, but this capacity is reduced in WAT cells from obese individuals.

  6. 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.…

  7. 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.

  8. Overweight and obesity are associated with neuronal injury in the human cerebellum and hippocampus in young adults: a combined MRI, serum marker and gene expression study.

    Science.gov (United States)

    Mueller, K; Sacher, J; Arelin, K; Holiga, S; Kratzsch, J; Villringer, A; Schroeter, M L

    2012-12-04

    There is growing evidence that obesity represents a risk for enhanced gray matter (GM) density changes comparable to those demonstrated for mild cognitive impairment in the elderly. However, it is not clear what mechanisms underlie this apparent alteration in brain structure of overweight subjects and to what extent these changes can already occur in the adolescent human brain. In the present volumetric magnetic resonance imaging study, we investigated GM changes and serum levels of neuron-specific enolase (NSE), a marker for neuronal injury, in a set of overweight/obese subjects and controls. We report a negative correlation for overweight and obese subjects between serum NSE and GM density in hippocampal and cerebellar regions. To validate our neuroimaging findings, we complement these data with NSE gene expression information obtained from the Allen Brain atlas. GM density changes were localized in brain areas that mediate cognitive function-the hippocampus associated with memory performance, and the cognitive cerebellum (lateral posterior lobes) associated with executive, spatial and linguistic processing. The data of our present study highlight the importance of extending current research on cognitive function and brain plasticity in the elderly in the context of obesity to young adult subjects and include serum biomarkers to validate imaging findings generally.

  9. 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

  10. Decreased MicroRNA-221 is Associated with High Levels of TNF-α in Human Adipose Tissue-Derived Mesenchymal Stem Cells From Obese Woman

    Directory of Open Access Journals (Sweden)

    Wen-Wen Chou

    2013-07-01

    Full Text Available Aim: The present study aimed to investigate the regulation and involvement of miR-221 in the differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs. The relationships between miR-221 and pro-inflammatory markers and adipokines were also explored. Methods: Eight adipose tissues were obtained from four obese (mean body mass index (BMI =31.7 kg/m2 and four lean (mean BMI= 21.5 kg/m2 women. hASCs were induced to differentiate, and the related gene expression were measured in the hASC-differentiated adipocytes using real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR. Results: During adipogenesis, miR-221 was significantly down-regulated; furthermore, miR-221 levels were lower in hASC-differentiated adipocytes from obese subjects than in the corresponding adipocytes from lean subjects. Higher TNF-α mRNA levels were associated with lower levels of miR-221. In addition, the miR-221 levels in the adipocytes were inversely correlated with BMI. Conclusion: Our results support the link between miR-221 and obesity development as well as obesity related inflammatory status.

  11. 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.

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

    Science.gov (United States)

    Respondek, Frederique; Gerard, Philippe; Bossis, Mathilde; Boschat, Laura; Bruneau, Aurélia; Rabot, Sylvie; Wagner, Anne; Martin, Jean-Charles

    2013-01-01

    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.

  13. [Asthma, obesity and diet].

    Science.gov (United States)

    Barranco, P; Delgado, J; Gallego, L T; Bobolea, I; Pedrosa, Ma; García de Lorenzo, A; Quirce, S

    2012-01-01

    Asthma and obesity have a considerable impact on public health and their prevalence has increased in recent years. Numerous studies have linked both disorders. Most prospective studies show that obesity is a risk factor for asthma and have found a positive correlation between baseline body mass index (BMI) and the subsequent development of asthma, although these results are not conclusive when studying the association between airway hyperresponsiveness with BMI. Furthermore, several studies suggest that whereas weight gain increases the risk of asthma, weight loss improves the course of the illness. Different factors could explain this association. Obesity is capable of reducing pulmonary compliance, lung volumes and the diameter of peripheral respiratory airways as well as affecting the volume of blood in the lungs and the ventilation-perfusion relationship. Furthermore, the increase in the normal functioning of adipose tissue in obese subjects leads to a systemic proinflammatory state, which produces a rise in the serum concentrations of several cytokines, the soluble fractions of their receptors and chemokines. Many of these mediators are synthesized and secreted by cells from adipose tissue and receive the generic name of adipokines, including IL-6, IL-10, eotaxin, TNF-α, TGF- 1, PCR, leptin y adiponectin. Finally, specific regions of the human genome which are related to both asthma and obesity have been identified. Most studies point out that obesity is capable of increasing the prevalence and incidence of asthma, although this effect appears to be modest. The treatment of obese asthmatics must include a weight control program.

  14. Childhood obesity.

    Science.gov (United States)

    Seth, Anju; Sharma, Rajni

    2013-04-01

    Childhood obesity is an issue of serious medical and social concern. In developing countries including India, it is a phenomenon seen in higher socioeconomic strata due to the adoption of a western lifestyle. Consumption of high calorie food, lack of physical activity and increased screen time are major risk factors for childhood obesity apart from other genetic, prenatal factors and socio-cultural practices. Obese children and adolescents are at increased risk of medical and psychological complications. Insulin resistance is commonly present especially in those with central obesity and manifests as dyslipidemia, type 2 diabetes mellitus, impaired glucose tolerance, hypertension, polycystic ovarian syndrome and metabolic syndrome. Obese children and adolescents often present to general physicians for management. The latter play a key role in prevention and treatment of obesity as it involves lifestyle modification of the entire family. This article aims at discussing the approach to diagnosis and work-up, treatment and preventive strategies for childhood obesity from a general physician's perspective.

  15. MAP3K8 (TPL2/COT affects obesity-induced adipose tissue inflammation without systemic effects in humans and in mice.

    Directory of Open Access Journals (Sweden)

    Dov B Ballak

    Full Text Available Chronic low-grade inflammation in adipose tissue often accompanies obesity, leading to insulin resistance and increasing the risk for metabolic diseases. MAP3K8 (TPL2/COT is an important signal transductor and activator of pro-inflammatory pathways that has been linked to obesity-induced adipose tissue inflammation. We used human adipose tissue biopsies to study the relationship of MAP3K8 expression with markers of obesity and expression of pro-inflammatory cytokines (IL-1β, IL-6 and IL-8. Moreover, we evaluated obesity-induced adipose tissue inflammation and insulin resistance in mice lacking MAP3K8 and WT mice on a high-fat diet (HFD for 16 weeks. Individuals with a BMI >30 displayed a higher mRNA expression of MAP3K8 in adipose tissue compared to individuals with a normal BMI. Additionally, high mRNA expression levels of IL-1β, IL-6 and IL-8, but not TNF -α, in human adipose tissue were associated with higher expression of MAP3K8. Moreover, high plasma SAA and CRP did not associate with increased MAP3K8 expression in adipose tissue. Similarly, no association was found for MAP3K8 expression with plasma insulin or glucose levels. Mice lacking MAP3K8 had similar bodyweight gain as WT mice, yet displayed lower mRNA expression levels of IL-1β, IL-6 and CXCL1 in adipose tissue in response to the HFD as compared to WT animals. However, MAP3K8 deficient mice were not protected against HFD-induced adipose tissue macrophage infiltration or the development of insulin resistance. Together, the data in both human and mouse show that MAP3K8 is involved in local adipose tissue inflammation, specifically for IL-1β and its responsive cytokines IL-6 and IL-8, but does not seem to have systemic effects on insulin resistance.

  16. Molecular Characterization of the Tumor Suppressor Candidate 5 Gene: Regulation by PPARγ and Identification of TUSC5 Coding Variants in Lean and Obese Humans

    Directory of Open Access Journals (Sweden)

    Trina A. Knotts

    2009-01-01

    Full Text Available Tumor suppressor candidate 5 (TUSC5 is a gene expressed abundantly in white adipose tissue (WAT, brown adipose tissue (BAT, and peripheral afferent neurons. Strong adipocyte expression and increased expression following peroxisome proliferator activated receptor γ (PPARγ agonist treatment of 3T3-L1 adipocytes suggested a role for Tusc5 in fat cell proliferation and/or metabolism. However, the regulation of Tusc5 in WAT and its potential association with obesity phenotypes remain unclear. We tested the hypothesis that the TUSC5 gene is a bona fide PPARγ target and evaluated whether its WAT expression or single-nucleotide polymorphisms (SNPs in the TUSC5 coding region are associated with human obesity. Induction of Tusc5 mRNA levels in 3T3-L1 adipocytes by troglitazone and GW1929 followed a dose-response consistent with these agents' binding affinities for PPARγ. Chromatin immunoprecipitation (ChIP experiments confirmed that PPARγ protein binds a ∼−1.1 kb promotor sequence of murine TUSC5 transiently during 3T3-L1 adipogenesis, concurrent with histone H3 acetylation. No change in Tusc5 mRNA or protein levels was evident in type 2 diabetic patients treated with pioglitazone. Tusc5 expression was not induced appreciably in liver preparations overexpressing PPARs, suggesting that tissue-specific factors regulate PPARγ responsiveness of the TUSC5 gene. Finally, we observed no differences in Tusc5 WAT expression or prevalence of coding region SNPs in lean versus obese human subjects. These studies firmly establish the murine TUSC5 gene locus as a PPARγ target, but the significance of Tusc5 in obesity phenotypes or in the pharmacologic actions of PPARγ agonists in humans remains equivocal.

  17. 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.

  18. Obesity and gastrointestinal neoplasms

    Directory of Open Access Journals (Sweden)

    Izabela Binkowska-Borgosz

    2014-10-01

    Full Text Available Being overweight or obese is a significant public health problem in the 21st century due to its scale, common existence and its cause-effect association with multiple diseases. Excessive accumulation of adipose tissue in humans is regarded as a major risk factor for development of cardiovascular and skeletal diseases. However, data from recent years have revealed that obesity is also strongly associated with increased risk of the majority of cancers in humans, including those originating from the gastrointestinal tract. During the last few year this association has been thoroughly proven and supported by several epidemiological analyses. The authors present i the current state of knowledge regarding key (pathomechanisms that link metabolism of human adipose tissue to development/progression of neoplasms (especially in the gastrointestinal tract, as well as ii the results of selected clinical studies in which the influence of obesity on risk of gastrointestinal cancer development has been addressed.

  19. Gut microbiota and obesity.

    Science.gov (United States)

    Gérard, Philippe

    2016-01-01

    The human intestine harbors a complex bacterial community called the gut microbiota. This microbiota is specific to each individual despite the existence of several bacterial species shared by the majority of adults. The influence of the gut microbiota in human health and disease has been revealed in the recent years. Particularly, the use of germ-free animals and microbiota transplant showed that the gut microbiota may play a causal role in the development of obesity and associated metabolic disorders, and lead to identification of several mechanisms. In humans, differences in microbiota composition, functional genes and metabolic activities are observed between obese and lean individuals suggesting a contribution of the gut microbiota to these phenotypes. Finally, the evidence linking gut bacteria to host metabolism could allow the development of new therapeutic strategies based on gut microbiota modulation to treat or prevent obesity.

  20. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain

    OpenAIRE

    Olesen, R H; Hyde, T M; Kleinman, J E; Smidt, K; Rungby, J; Larsen, A.

    2016-01-01

    The incidence of Alzheimer's disease (AD) is increasing. Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia. Obese and diabetic individuals are prone to decreased circulating levels of zinc, reducing the amount of zinc available for crucial intracellular processes. In the brain, zinc co-localizes with glutamate in synaptic vesicles, and modulates NMDA receptor activity. Intracellular zinc is involved in apoptosis an...

  1. Rare genetic diseases with human lean and/or starvation phenotype open new avenues for obesity and type II diabetes treatment.

    Science.gov (United States)

    Harosh, Itzik

    2014-01-01

    Treatments of obesity and type II diabetes target often gene functions involved in appetite-satiety, fat and carbohydrate metabolism or thermogenesis. None of these, have provided efficient drug therapy due to a large number of genes involved in weight and energy management, the redundancy of biochemical pathways and the environmental factors. Here I discuss a new approach based on studies of genes/proteins that are associated with human "lean or starvation" phenotype that became very rare in the course of evolution. This approach has led to the identification of the congenital enteropeptidase deficiency gene and the Anderson's Disease gene as a potential targets for obesity and type II diabetes treatment. The advantages of these targets are: 1) they are expressed exclusively in the intestine; 2) they are peripheral targets as opposed to systemic targets; 3) they are not redundant targets. These targets open new hopes for the development of novel drugs for the treatment of common metabolic syndrome.

  2. [Expression of human insulin in lactic acid bacteria and its oral administration in non-obese diabetic mice].

    Science.gov (United States)

    Chen, Si-Wei; Zhong, Jin; Huan, Lian-Dong

    2007-12-01

    Type 1 diabetes mellitus (T1DM) is an auto-immune disease while oral administrating its autoantigens could be a treatment of T1DM. To express human insulin gene (ins) in lactic acid bacteria (LAB) for oral vaccine, ins gene was replaced by LAB bias codon and an 8-amino-acid-residue linker peptide forming a beta-turn was designed to link insulin chain A and B. After synthesized by primer annealing method, the whole ins gene was fused with signal peptide sequence SP(Usp45), subcloned into a LAB secretory expressive vector pSW501 and then introduced to Lactococcus lactis (L. lactis) MG1363 and Lactobacillus casei (Lb. casei ) ATCC27092 respectively. Western blot showed that the expression product (SP(Usp45)-INS protein) targeted mainly at the cell wall while little was found in cytoplasm or supernatant. The highest expression level emerged in exponential phase when the optical density at 600nm of the culture was 0.4. The culture of the recombinant strain Lb. casei/pSW501 was administered to non-obese diabetic (NOD) mice orally. ELISA and Western blot results showed that the recombinant strain could induce SP(Usp45)-INS-specific antibodies and raise IL-4 level (38.583 +/- 2.083 pg/mL, P < 0.05) in the mice' s sera. Expression of insulin in the food-grade vehicle LAB could induce oral immune tolerance in NOD mice and protect it from pancreas injury, suggesting it might be a new way to the treatment of T1DM.

  3. Hypertension in obesity: is leptin the culprit?

    Science.gov (United States)

    Simonds, Stephanie E; Cowley, Michael A

    2013-02-01

    The number of obese or overweight humans continues to increase worldwide. Hypertension is a serious disease that often develops in obesity, but it is not clear how obesity increases the risk of hypertension. However, both obesity and hypertension increase the risk of cardiovascular diseases (CVD). In this review, we examine how obesity may increase the risk of developing hypertension. Specifically, we discuss how the adipose-derived hormone leptin influences the sympathetic nervous system (SNS), through actions in the brain to elevate energy expenditure (EE) while also contributing to hypertension in obesity.

  4. Obesity Statistics.

    Science.gov (United States)

    Smith, Kristy Breuhl; Smith, Michael Seth

    2016-03-01

    Obesity is a chronic disease that is strongly associated with an increase in mortality and morbidity including, certain types of cancer, cardiovascular disease, disability, diabetes mellitus, hypertension, osteoarthritis, and stroke. In adults, overweight is defined as a body mass index (BMI) of 25 kg/m(2) to 29 kg/m(2) and obesity as a BMI of greater than 30 kg/m(2). If current trends continue, it is estimated that, by the year 2030, 38% of the world's adult population will be overweight and another 20% obese. Significant global health strategies must reduce the morbidity and mortality associated with the obesity epidemic.

  5. 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

    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......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...

  6. Obesity-insulin targeted genes in the 3p26-25 region in human studies and LG/J and SM/J mice.

    Science.gov (United States)

    Kraja, Aldi T; Lawson, Heather A; Arnett, Donna K; Borecki, Ingrid B; Broeckel, Ulrich; de las Fuentes, Lisa; Hunt, Steven C; Province, Michael A; Cheverud, James; Rao, D C

    2012-08-01

    Identifying metabolic syndrome (MetS) genes is important for novel drug development and health care. This study extends the findings on human chromosome 3p26-25 for an identified obesity-insulin factor QTL, with an LOD score above 3. A focused association analysis comprising up to 9578 African American and Caucasian subjects from the HyperGEN Network (908 African Americans and 1025 whites), the Family Heart Study (3035 whites in time 1 and 1943 in time 2), and the Framingham Heart Study (1317 in Offspring and 1320 in Generation 3) was performed. The homologous mouse region was explored in an F(16) generation of an advanced intercross between the LG/J and SM/J inbred strains, in an experiment where 1002 animals were fed low-fat (247 males; 254 females) or high-fat (253 males; 248 females) diets. Association results in humans indicate pleiotropic effects for SNPs within or surrounding CNTN4 on obesity, lipids and blood pressure traits and for SNPs near IL5RA, TRNT1, CRBN, and LRRN1 on central obesity and blood pressure. Linkage analyses of this region in LG/J×SM/J mice identify a highly significant pleiotropic QTL peak for insulin and glucose levels, as well as response to glucose challenge. The mouse results show that insulin and glucose levels interact with high and low fat diets and differential gene expression was identified for Crbn and Arl8b. In humans, ARL8B resides ~137kbps away from BHLHE40, expression of which shows up-regulation in response to insulin treatment. This focused human genetic analysis, incorporating mouse research evidenced that 3p26-25 has important genetic contributions to MetS components. Several of the candidate genes have functions in the brain. Their interaction with MetS and the brain warrants further investigation.

  7. Dietary Polyphenols and Obesity

    Directory of Open Access Journals (Sweden)

    Mohsen Meydani

    2010-07-01

    Full Text Available The prevalence of overweight and obesity and their associated metabolic disorders are considered a major threat to the public’s health. While several diet and exercise programs are available for weight loss and prevention of weight regain, progress is often slow and disappointing. Recently, natural bioactive phytochemicals present in foods have been discovered for their potential health benefit effects on the prevention of chronic disorders such as cancer, cardiovascular disease, inflammatory and metabolic diseases including obesity.Polyphenols are a class of naturally-occurring phytochemicals, of which some such as catechins, anthocynines, resveratrol and curcumin have been shown to modulate physiological and molecular pathways that are involved in energy metabolism, adiposity, and obesity. The potential in vivo, beneficial effects of these polyphenols on adiposity and obesity as complementary agents in the up-regulation of energy expenditure have emerged by investigating these compounds in cell cultures, animal models of obesity and in some human clinical and epidemiological studies. In this brief review, the efficacy of the above-named polyphenols and their potential efficacy to modulate obesity and some associated disorders are discussed.

  8. Prebiotics in obesity.

    Science.gov (United States)

    Carnahan, S; Balzer, A; Panchal, S K; Brown, L

    2014-06-01

    Obesity was probably rare in ancient times, with the current increase starting in the Industrial Revolution of the eighteenth century, and becoming much more widespread from about 1950, so concurrent with the increased consumption of carbohydrates from cereals in the Green Revolution. However, dietary components such as oligosaccharides from plants including cereals may improve health following fermentation to short-chain carboxylic acids in the intestine by bacteria which constitute of the microbiome. Such non-digestible and fermentable components of diet, called prebiotics, have been part of the human diet since at least Palaeolithic times, and include components of the cereals domesticated in the Neolithic Revolution. If consumption of these cereals has now increased, why is obesity increasing? One reason could be lowered prebiotic intake combined with increased intake of simple sugars, thus changing the bacteria in the microbiome. Processing of food has played an important role in this change of diet composition. Since obesity is a low-grade inflammation, changing the microbiome by increased consumption of simple carbohydrates and saturated fats may lead to obesity via increased systemic inflammation. Conversely, there is now reasonable evidence that increased dietary prebiotic intake decreases inflammation, improves glucose metabolism and decreases obesity. Would widespread increases in prebiotics in the modern diet, so mimicking Palaeolithic or Neolithic nutrition, decrease the incidence and morbidity of obesity in our communities?

  9. Use of pyrosequencing and DNA barcodes to monitor variations in Firmicutes and Bacteroidetes communities in the gut microbiota of obese humans

    Directory of Open Access Journals (Sweden)

    Raoult Didier

    2008-12-01

    Full Text Available Abstract Background Recent studies of 16S rRNA genes in the mammalian gut microbiota distinguished a higher Firmicutes/Bacteroidetes ratio in obese individuals compared to lean individuals. This ratio was estimated using a clonal Sanger sequencing approach which is time-consuming and requires laborious data analysis. In contrast, new high-throughput pyrosequencing technology offers an inexpensive alternative to clonal Sanger sequencing and would significantly advance our understanding of obesity via the development of a clinical diagnostic method. Here we present a cost-effective method that combines 16S rRNA pyrosequencing and DNA barcodes of the Firmicutes and Bacteroidetes 16S rRNA genes to determine the Firmicutes/Bacteroidetes ratio in the gut microbiota of obese humans. Results The main result was the identification of DNA barcodes targeting the Firmicutes and Bacteroidetes phyla. These barcodes were validated using previously published 16S rRNA gut microbiota clone libraries. In addition, an accurate F/B ratio was found when the DNA barcodes were applied to short pyrosequencing reads of published gut metagenomes. Finally, the barcodes were utilized to define the F/B ratio of 16S rRNA pyrosequencing data generated from brain abscess pus and cystic fibrosis sputum. Conclusion Using DNA barcodes of Bacteroidetes and Firmicutes 16S rRNA genes combined with pyrosequencing is a cost-effective method for monitoring relevant changes in the relative abundance of Firmicutes and Bacteroidetes bacterial communities in microbial ecosystems.

  10. 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.

  11. 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.

  12. 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

    2016-01-01

    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-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. PMID:27304953

  13. 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

    OBJECTIVE: Pre-receptor amplification of glucocorticoids is, in part, determined by the isoenzymes 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and type 2, interconverting inert cortisone and active cortisol. Increased tissue activity of cortisol may play a part in features...... 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...... abdominal surgery (lean men, 10), minor gynecological surgery (lean woman, 10), or gastric banding operations (obese men, 10; and obese women, 10). Gene expressions of 11beta-HSD1 in adipose tissue samples were determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Lean...

  14. Childhood obesity.

    Science.gov (United States)

    Strauss, R

    1999-01-01

    Approximately 10% of children are obese. Twin and adoption studies demonstrate a large genetic component to obesity, especially in adults. However, the increasing prevalence of obesity over the last 20 years can only be explained by environmental factors. In most obese individuals, no measurable differences in metabolism can be detected. Few children engage in regular physical activity. Obese children and adults uniformly underreport the amount of food they eat. Obesity is particularly related to increased consumption of high-fat foods. BMI is a quick and easy way to screen for childhood obesity. Treating childhood obesity relies on positive family support and lifestyle changes involving the whole family. Food preferences are influenced early by parental eating habits, and when developed in childhood, they tend to remain fairly constant into adulthood. Children learn to be active or inactive from their parents. In addition, physical activity (or more commonly, physical inactivity) habits that are established in childhood tend to persist into adulthood. Weight loss is usually followed by changes in appetite and metabolism, predisposing individuals to regain their weight. However, when the right family dynamics exist--a motivated child with supportive parents--long-term success is possible.

  15. A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance

    OpenAIRE

    Newgard, Christopher B.; An, Jie; Bain, James R.; Muehlbauer, Michael J.; Robert D. Stevens; Lien, Lillian F.; Haqq, Andrea M.; Shah, Svati H.; Arlotto, Michelle; Slentz, Cris A.; Rochon, James; Gallup, Dianne; Ilkayeva, Olga; Brett R. Wenner; Yancy, William E

    2009-01-01

    Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with insulin resistance. To test its impact on metabolic homeostasis, we fed rats on high-fat (HF), HF with supplemented BCAA (HF/BCAA) or standard chow (SC) diets. Despite having reduced food intake and weight gain equivalent to the SC group, HF/BCAA rats were equally insulin resistant as HF rats. Pair-feed...

  16. 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

  17. 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...... chromosome (SSC) 14 was very strongly associated with NVD (p =9.6E-07). Thirty six SNPs were located in genome regions where QTLs havepreviously been reported...... 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...

  18. Preclinical models for obesity research.

    Science.gov (United States)

    Barrett, Perry; Mercer, Julian G; Morgan, Peter J

    2016-11-01

    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.

  19. 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.

  20. 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

  1. Adipose tissue gene expression is differentially regulated with different rates of weight loss in overweight and obese humans

    NARCIS (Netherlands)

    Vink, R G; Roumans, N J; Fazelzadeh, P; Tareen, S H K; Boekschoten, M V; van Baak, M A; Mariman, E C

    2016-01-01

    BACKGROUND/OBJECTIVES: Moderate weight loss (WL) can ameliorate adverse health effects associated with obesity, reflected by an improved adipose tissue (AT) gene expression profile. However, the effect of rate of WL on the AT transcriptome is unknown. We investigated the global AT gene expression pr

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

    NARCIS (Netherlands)

    Diamant, M.; Vaughan, E.E.; Vos, de 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 lipid-metabolism

  3. 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, M F; Wellner, Niels; Ahmed, Shamaila Saghir;

    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)....

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

    Science.gov (United States)

    Koppo, Katrien; Larrouy, Dominique; Marques, Marie A; Berlan, Michel; Bajzova, Magda; Polak, Jan; Van de Voorde, Johan; Bülow, Jens; Lafontan, Max; Crampes, François; Langin, Dominique; Stich, Vladimir; de Glisezinski, Isabelle

    2010-08-01

    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 cycle exercise bout at 50% of their peak oxygen uptake on two occasions: during intravenous infusion of octreotide (a somatostatin analog) or physiological saline (control condition). Lipolysis in SCAT was evaluated using in situ microdialysis. One microdialysis probe was perfused with the adrenergic blockers phentolamine and propranolol while another probe was perfused with the phosphodiesterase and adenosine receptor inhibitor aminophylline. Compared with the control condition, infusion of octreotide reduced plasma insulin levels in lean (from approximately 3.5 to 0.5 microU/ml) and in obese (from approximately 9 to 2 microU/ml), blunted the exercise-induced rise in plasma GH and epinephrine levels in both groups, and enhanced the exercise-induced natriuretic peptide (NP) levels in lean but not in obese subjects. In both groups, octreotide infusion resulted in higher exercise-induced increases in dialysate glycerol concentrations in the phentolamine-containing probe while no difference in lipolytic response was found in the aminophylline-containing probe. The results suggest that insulin antilipolytic action plays a role in the regulation of lipolysis during exercise in lean as well as in obese subjects. The octreotide-induced enhancement of exercise lipolysis in lean subjects was associated with an increased exercise-induced plasma NP response. Adenosine may contribute to the inhibition of basal lipolysis in both subject groups.

  5. 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)

    Science.gov (United States)

    Pu, Shuaihua; Khazanehei, Hamidreza; Jones, Peter J.; Khafipour, Ehsan

    2016-01-01

    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, 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 16S rRNA gene pyrosequencing. A total of 17 phyla and 187 genera were identified. While five novel oil treatments failed to alter bacterial phyla composition, obese participants resulted in 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’s populations, while the two PUFA-rich diets favored the higher 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 profile, and that MUFA-rich and PUFA-rich diets impact the composition of gut microbiota at lower

  6. 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.

    2011-01-01

    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

  7. 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

  8. 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.

  9. Maternal obesity and prenatal programming.

    Science.gov (United States)

    Elshenawy, Summer; Simmons, Rebecca

    2016-11-05

    Obesity is a significant and increasing public health concern in the United States and worldwide. Clinical and epidemiological evidence clearly shows that genetic and environmental factors contribute to the increased susceptibility of humans to obesity and its associated comorbidities; the interplay of these factors is explained by the concept of epigenetics. The impact of maternal obesity goes beyond the newborn period; fetal programming during the critical window of pregnancy, can have long term detrimental effects on the offspring as well as future generations. Emerging evidence is uncovering a link between the clinical and molecular findings in the offspring with epigenetic changes in the setting of maternal obesity. Research targeted towards reducing the transgenerational propagation and developmental programming of obesity is vital in reducing the increasing rates of disease.

  10. Obesity & osteoarthritis

    OpenAIRE

    King, Lauren K.; Lyn March; Ananthila Anandacoomarasamy

    2013-01-01

    The most significant impact of obesity on the musculoskeletal system is associated with osteoarthritis (OA), a disabling degenerative joint disorder characterized by pain, decreased mobility and negative impact on quality of life. OA pathogenesis relates to both excessive joint loading and altered biomechanical patterns together with hormonal and cytokine dysregulation. Obesity is associated with the incidence and progression of OA of both weight-bearing and non weight-bearing joints, to rate...

  11. Childhood obesity

    OpenAIRE

    Wilkinson, Justine; Howard, Simon

    2006-01-01

    Childhood obesity has important consequences for health and wellbeing both during childhood and also in later adult life. The rising prevalence of childhood obesity poses a major public health challenge in both developed and developing countries by increasing the burden of chronic non-communicable diseases. Despite the urgent need for effective preventative strategies, there remains disagreement over its definition due to a lack of evidence on the optimal cut-offs linking childhood BMI to dis...

  12. 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

    to 2 microU/ml), blunted the exercise-induced rise in plasma GH and epinephrine levels in both groups, and enhanced the exercise-induced natriuretic peptide (NP) levels in lean but not in obese subjects. In both groups, octreotide infusion resulted in higher exercise-induced increases in dialysate...... glycerol concentrations in the phentolamine-containing probe while no difference in lipolytic response was found in the aminophylline-containing probe. The results suggest that insulin antilipolytic action plays a role in the regulation of lipolysis during exercise in lean as well as in obese subjects....... The octreotide-induced enhancement of exercise lipolysis in lean subjects was associated with an increased exercise-induced plasma NP response. Adenosine may contribute to the inhibition of basal lipolysis in both subject groups....

  13. Artificial synthesis and cloning of human obese gene%人肥胖(obese)基因的人工合成及克隆

    Institute of Scientific and Technical Information of China (English)

    杨林; 吴无畏

    2000-01-01

    根据人肥胖基因的cDNA序列,通过合理的引物设计、链延伸反应、PCR反应以及分子克隆等步骤,成功地合成出编码瘦蛋白(Leptin)的肥胖基因(ob基因)全长片段,并将其克隆至pUC18载体质粒上.序列分析和酶切鉴定显示肥胖基因得到了正确合成和克隆.%According to the known sequence of human ob gene cDNA,the gene coding the leptin was synthesized and cloned into pUC18 vector after reasonable primer designing,DNA strain extending,PCR reaction and molecular cloning.Sequence analysis and RE digest results showed the ob gene was synthesized and cloned correctly.

  14. 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...

  15. Identification of Direct and Indirect Social Network Effects in the Pathophysiology of Insulin Resistance in Obese Human Subjects

    OpenAIRE

    Henning, Christian H.C.A.; Nana Zarnekow; Johannes Hedtrich; Sascha Stark; Kathrin Türk; Matthias Laudes

    2014-01-01

    OBJECTIVE: The aim of the present study was to examine to what extent different social network mechanisms are involved in the pathogenesis of obesity and insulin-resistance. DESIGN: We used nonparametric and parametric regression models to analyse whether individual BMI and HOMA-IR are determined by social network characteristics. SUBJECTS AND METHODS: A total of 677 probands (EGO) and 3033 social network partners (ALTER) were included in the study. Data gathered from the probands include ant...

  16. Differences in insula and pre-/frontal responses during reappraisal of food in lean and obese humans

    Directory of Open Access Journals (Sweden)

    Saurabh eKumar

    2016-05-01

    Full Text Available Brain regions involved in the reappraisal of tasty but unhealthy foods are of special interest for the development of new therapeutic interventions for obesity, such as non-invasive brain stimulation or neurofeedback. Here, we visually presented food items (i.e., high/low caloric to obese and lean individuals during EEG recordings, while they either admitted or regulated their food desire. During admitting the desire for low and high calorie foods, obese as well as lean individuals showed higher activity in the left dorsolateral prefrontal cortex (DLPFC, whereas the right frontal operculum was involved in the reappraisal of the same foods, suggesting interplay between executive control and gustatory regions. Only in lean participants, we found an interaction between calorie content and the regulate/admit conditions in bilateral anterior insular cortices, suggesting that the anterior insula, assumed to primarily host gustatory processes, also underpins higher cognitive processes involved in food choices, such as evaluating the foods’ calorie content for its reappraisal.

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

    Science.gov (United States)

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

    2011-04-01

    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 lipid-metabolism. Data, mostly derived from preclinical studies, suggest that gut microbiota play an important role in conditions such as obesity, diabetes, metabolic syndrome and non-alcoholic fatty liver disease. Regulation of energy uptake from the gut, by digesting otherwise indigestible common polysaccharides in our diet, production or activation of signalling molecules involved in host metabolism, modification of gut permeability, the release of gut hormones and inflammation, are among the mechanisms by which gut microbiota may influence the host cardiometabolic phenotype. Recent evidence suggests that quantitative and qualitative differences in gut microbiota exist between lean and obese, and between diabetic and non-diabetic individuals. Modification of the gut microbiota composition and/or its biochemical capacity by specific dietary or pharmacological interventions may favourably affect host metabolism. Large-scale intervention trials, investigating the potential benefit of prebiotics and probiotics in improving cardiometabolic health in high-risk populations, are eagerly awaited.

  18. 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.

  19. 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.

  20. Human-Specific SNP in Obesity Genes, Adrenergic Receptor Beta2 (ADRB2), Beta3 (ADRB3), and PPAR γ2 (PPARG), during Primate Evolution

    Science.gov (United States)

    Takenaka, Akiko; Nakamura, Shin; Mitsunaga, Fusako; Inoue-Murayama, Miho; Udono, Toshifumi; Suryobroto, Bambang

    2012-01-01

    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. PMID:22937051

  1. Chronobiology and obesity.

    Science.gov (United States)

    Garaulet, Marta; Gómez-Abellán, Purificación

    2013-09-01

    Chronobiology is a word derived from three Greek stems: kronos for time, bios for life and logos for study. From microarrays studies, now it is accepted that 10-30% of the human genome is under the control of circadian molecular clocks. This implies that most behavioral, physiological and biochemical variables display circadian rhythms in their expression. In its simplest form, circadian clocks are composed of a set of proteins that generate self-sustained circadian oscillations. The molecular clock comprises two transcription factors, CLOCK and BMAL1, whereas PERs and CRYs are responsible for the negative limb. One of the most important questions related to the circadian system and obesity, was to elucidate if adipose tissue displayed circadian rhythmicity or whether it had an internal peripheral clock. Our group of research has provided an overall view of the internal temporal order of circadian rhythms in human adipose tissue. A new concept related to illness is Chronodisruption (CD). It is defined as a relevant disturbance of the internal temporal order of physiological and behavioral circadian rhythms. In our modern society, CD may be common in several conditions such as jet lag, shift work, light at night, or social jet lag. In addition clock gene polymorphisms and aging may have also chronodisruptive effects. Our group has also demonstrated that Obesity and CD are also highly interconnected. With the help of chronobiology we can reach a new view of obesity considering not only "what" are the factors involved in obesity, but also "when" these factors are produced.

  2. Microsatellite Marker Content Mapping of 12 Candidate Genes for Obesity: Assembly of Seven Obesity Screening Panels for Automated Genotyping

    OpenAIRE

    Winick, Jeffrey D.; Friedman, Jeffrey M.

    1998-01-01

    Twin studies, adoption studies, and studies of familial aggregation indicate that obesity has a genetic component. Whereas, the genetic factors predisposing to obesity have been elucidated for several rare syndromes, the factors responsible for obesity in the general population have remained elusive. Genetic studies of complex traits are often accelerated by the use of candidate genes. To facilitate genetic studies of human obesity, seven multiplex panels of candidate genes for obesity that a...

  3. Hormones and Obesity

    Science.gov (United States)

    ... Balance › Hormones and Obesity Fact Sheet Hormones and Obesity March, 2010 Download PDFs English Espanol Editors Caroline Apovian, MD Judith Korner, MD, PhD What is obesity? Obesity is a chronic (long-term) medical problem ...

  4. Obesity and Physical Modalities

    OpenAIRE

    Kokino, Siranuş; Özdemir, Ferda; Zateri, Coşkun

    2006-01-01

    The prevalence of obesity is increasing. It is one of the commonest pathologies in developed countries. In general, obesity is caused by an imbalance between energy obtained by food and energy expended. A sedentary life-style is also associated with obesity and obesity-related chronic diseases. The result of childhood obesity is adult obesity, so obesity should be treated early. Obesity is a complex problem and effective treatment will probably require incorporation of different approaches. I...

  5. [Obesity paradox].

    Science.gov (United States)

    Aursulesei, Viviana; Cozma, A; Datcu, M D

    2009-01-01

    Obesity has reached global epidemic proportions and is associated with major cardiovascular diseases and reduced overall survival. This paper reviews the metabolic and vascular consequences of dysfunctional adipocytokines in obesity as well as the pathological effects on blood pressure, cardiovascular structure and function. Despite this adverse association, numerous studies have documented an obesity paradox in which overweight and obese population with established cardiovascular disease have a better prognosis. There are potential explanations offered by literature for these puzzling data. For obese hypertensive patients the paradox is possibly linked to the lower systemic vascular resistance and plasma renin activity. In heart failure the excess body weight may confer some protective effects on mortality, due to a more metabolic reserve, higher levels of arterial pressure compatible with higher doses of cardioprotective medications, and a specific neuroendocrine profile with lower levels of circulating natriuretic atrial peptides, attenuated sympathetic nervous system and renin-angiotensin responses. For coronary heart disease and peripheral arterial disease the mechanisms are still uncertain. There are discussed a lesser severity of coronary lesions and left ventricular dysfunction, or a reduced prevalence of moderate-severe chronic obstructive pulmonary disease in patients selected for surgery. On the other hand, the constellation of data which supports purposeful weight reduction in the prevention and treatment of cardiovascular diseases, induces a controversial position regarding this new concept.

  6. Relationship of age and body mass index to the expression of obesity and osteoarthritis related genes in human meniscus

    Science.gov (United States)

    Rai, Muhammad Farooq; Sandell, Linda J.; Cheverud, James M.; Brophy, Robert H.

    2012-01-01

    Objective Aging and obesity contribute to the initiation and progression of osteoarthritis with little information on their relation to gene expression in joint tissues, particularly the meniscus. Here, we test the hypothesis that patient age and body mass index (BMI) correlate with the expression of osteoarthritis- and obesity-related gene signatures in the meniscus. Design Meniscus was obtained from patients (N=68) undergoing arthroscopic partial meniscectomy. The mRNA expression of twenty-four osteoarthritis-related and four obesity-related genes in meniscus was assessed by qRT-PCR. The relationship between gene expression and patient age and BMI was analyzed using Spearman’s rank-order correlation. Hierarchical cluster dendrogram and heat maps were generated to study inter-gene associations. Results Age was negatively correlated (P<0.05) with the expression of MMP-1 (r=−0.447), NFκB2 (r=−0.361), NFκBIA (r=−0.312), IκBA (r=−0.308), IL-8 (r=−0.305), ADAMTS-4 (r=−0.294), APLN (r=−0.250) and IL-6 (r=−0.244). Likewise, BMI was negatively correlated with the expression of APLN (r=−0.328), ACAN (r=−0.268) and MMP-1 (r=−0.261). After adjusting for the correlation between age and BMI (r=0.310; P=0.008), the only independent effect of BMI on gene expression was for APLN (r=−0.272). However, age had an independent effect on expression on ADAMTS-4 (r=−0.253), MMP-1 (r=−0.399), IL-8 (r=−0.327), COL1A1 (r=−0.287), NFκBIA (r=−0.278), NFκB2 (r=−0.312) and IκBA (r=−0.299). The gene-correlation analysis identified four clusters of potentially relevant genes: transcription factors, matrix degrading enzymes, cytokines and chemokines, and obesity genes. Conclusion Age and BMI were negatively correlated with several osteoarthritis- and obesity-related genes. While the bulk of these changes appeared to be driven by age, expression of APLN was related to BMI. Inter-gene correlations implicated a common regulatory role of strongly

  7. Human immune system development and survival of non-obese diabetic (NOD)-scid IL2rγ(null) (NSG) mice engrafted with human thymus and autologous haematopoietic stem cells.

    Science.gov (United States)

    Covassin, L; Jangalwe, S; Jouvet, N; Laning, J; Burzenski, L; Shultz, L D; Brehm, M A

    2013-12-01

    Immunodeficient mice bearing targeted mutations in the IL2rg gene and engrafted with human immune systems are effective tools for the study of human haematopoiesis, immunity, infectious disease and transplantation biology. The most robust human immune model is generated by implantation of human fetal thymic and liver tissues in irradiated recipients followed by intravenous injection of autologous fetal liver haematopoietic stem cells [often referred to as the BLT (bone marrow, liver, thymus) model]. To evaluate the non-obese diabetic (NOD)-scid IL2rγ(null) (NSG)-BLT model, we have assessed various engraftment parameters and how these parameters influence the longevity of NSG-BLT mice. We observed that irradiation and subrenal capsule implantation of thymus/liver fragments was optimal for generating human immune systems. However, after 4 months, a high number of NSG-BLT mice develop a fatal graft-versus-host disease (GVHD)-like syndrome, which correlates with the activation of human T cells and increased levels of human immunoglobulin (Ig). Onset of GVHD was not delayed in NSG mice lacking murine major histocompatibility complex (MHC) classes I or II and was not associated with a loss of human regulatory T cells or absence of intrathymic cells of mouse origin (mouse CD45(+) ). Our findings demonstrate that NSG-BLT mice develop robust human immune systems, but that the experimental window for these mice may be limited by the development of GVHD-like pathological changes.

  8. The intestinal microbiota and obesity.

    Science.gov (United States)

    Kallus, Samuel J; Brandt, Lawrence J

    2012-01-01

    Obesity has been and continues to be an epidemic in the United States. Obesity has been addressed in multiple health initiatives, including Healthy People 2010, with no state meeting the proposed goal of a prevalence of obesity fad diets, incentive-based exercise programs, and gastric bypass surgery; none of which have been optimal. In a murine model, it was shown that the majority of the intestinal microbiome consists of two bacterial phyla, the Bacteroidetes and the Firmicutes, and that the relative abundance of these two phyla differs among lean and obese mice; the obese mouse had a higher proportion of Firmicutes to Bacteroidetes (50% greater) than the lean mouse. The same results were appreciated in obese humans compared to lean subjects. The postulated explanation for this finding is that Firmicutes produce more complete metabolism of a given energy source than do Bacteroidetes, thus promoting more efficient absorption of calories and subsequent weight gain. Researchers were able to demonstrate that colonizing germ-free mice with the intestinal microbiome from obese mice led to an increased total body fat in the recipient mice despite a lack of change in diet. The converse, that, colonizing germ-free obese mice with the intestinal microbiome of thin mice causing a decreased total body fat in the recipient mice, has not yet been done. Other possible mechanisms by which the intestinal microbiome affects host obesity include induction of low-grade inflammation with lipopolysaccharide, regulation of host genes responsible for energy expenditure and storage, and hormonal communication between the intestinal microbiome and the host. The following review discusses the microbiome-obesity relationship and proposed mechanisms by which the intestinal microbiota is hypothesized to influence weight gain.

  9. T-cell receptor gene therapy targeting melanoma-associated antigen-A4 inhibits human tumor growth in non-obese diabetic/SCID/γcnull mice.

    Science.gov (United States)

    Shirakura, Yoshitaka; Mizuno, Yukari; Wang, Linan; Imai, Naoko; Amaike, Chisaki; Sato, Eiichi; Ito, Mamoru; Nukaya, Ikuei; Mineno, Junichi; Takesako, Kazutoh; Ikeda, Hiroaki; Shiku, Hiroshi

    2012-01-01

    Adoptive cell therapy with lymphocytes that have been genetically engineered to express tumor-reactive T-cell receptors (TCR) is a promising approach for cancer immunotherapy. We have been exploring the development of TCR gene therapy targeting cancer/testis antigens, including melanoma-associated antigen (MAGE) family antigens, that are ideal targets for adoptive T-cell therapy. The efficacy of TCR gene therapy targeting MAGE family antigens, however, has not yet been evaluated in vivo. Here, we demonstrate the in vivo antitumor activity in immunodeficient non-obese diabetic/SCID/γc(null) (NOG) mice of human lymphocytes genetically engineered to express TCR specific for the MAGE-A4 antigen. Polyclonal T cells derived from human peripheral blood mononuclear cells were transduced with the αβ TCR genes specific for MAGE-A4, then adoptively transferred into NOG mice inoculated with MAGE-A4 expressing human tumor cell lines. The transferred T cells maintained their effector function in vivo, infiltrated into tumors, and inhibited tumor growth in an antigen-specific manner. The combination of adoptive cell therapy with antigen peptide vaccination enhanced antitumor activity, with improved multifunctionality of the transferred cells. These data suggest that TCR gene therapy with MAGE-A4-specific TCR is a promising strategy to treat patients with MAGE-A4-expressing tumors; in addition, the acquisition of multifunctionality in vivo is an important factor to predict the quality of the T-cell response during adoptive therapy with human lymphocytes.

  10. 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.

  11. 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...... (1881-1968) wrote, "The biggest problem in the world could have been solved when it was small"....

  12. Prevalence of asymptomatic urinary tract infections in morbidly obese dogs

    OpenAIRE

    Wynn, Susan G.; Angela L. Witzel; Joseph W. Bartges; Tamberlyn S. Moyers; Claudia A. Kirk

    2016-01-01

    Background. Obesity has reached epidemic proportions in dogs and, as in humans, cost of care has increased due to associated comorbidities. In humans, asymptomatic urinary tract infections (UTI) may be more prevalent in the obese. Asymptomatic bacteriuria (AB) is the term used when UTI are asymptomatic. We hypothesized that morbidly obese dogs are similarly more likely to have asymptomatic bacteriuria than lean, overweight, and moderately obese dogs. Methods. A retrospective study was underta...

  13. Childhood Obesity

    Centers for Disease Control (CDC) Podcasts

    2013-08-06

    In this podcast, Dr. Tom Frieden, CDC Director, discusses the decrease in childhood obesity rates and what strategies have been proven to work to help our children grow up and thrive.  Created: 8/6/2013 by National Center for Injury Prevention and Control.   Date Released: 3/6/2014.

  14. Relationships of Adrenoceptor Polymorphisms with Obesity

    OpenAIRE

    Kazuko Masuo; Lambert, Gavin W.

    2011-01-01

    Obesity, hypertension, and type 2 diabetes are rapidly growing public health problems. Heightened sympathetic nerve activity is a well-established observation in obesity, hypertension, and type 2 diabetes. Human obesity, hypertension, and diabetes have strong genetic as well as environmental determinants. Reduced energy expenditure and resting metabolic rate are predictive of weight gain, and the sympathetic nervous system participates in regulating energy balance through thermogenesis. The t...

  15. 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.

  16. 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.

  17. Obesity & osteoarthritis.

    Science.gov (United States)

    King, Lauren K; March, Lyn; Anandacoomarasamy, Ananthila

    2013-01-01

    The most significant impact of obesity on the musculoskeletal system is associated with osteoarthritis (OA), a disabling degenerative joint disorder characterized by pain, decreased mobility and negative impact on quality of life. OA pathogenesis relates to both excessive joint loading and altered biomechanical patterns together with hormonal and cytokine dysregulation. Obesity is associated with the incidence and progression of OA of both weight-bearing and non weight-bearing joints, to rate of joint replacements as well as operative complications. Weight loss in OA can impart clinically significant improvements in pain and delay progression of joint structural damage. Further work is required to determine the relative contributions of mechanical and metabolic factors in the pathogenesis of OA.

  18. Obesity & osteoarthritis

    Directory of Open Access Journals (Sweden)

    Lauren K King

    2013-01-01

    Full Text Available The most significant impact of obesity on the musculoskeletal system is associated with osteoarthritis (OA, a disabling degenerative joint disorder characterized by pain, decreased mobility and negative impact on quality of life. OA pathogenesis relates to both excessive joint loading and altered biomechanical patterns together with hormonal and cytokine dysregulation. Obesity is associated with the incidence and progression of OA of both weight-bearing and non weight-bearing joints, to rate of joint replacements as well as operative complications. Weight loss in OA can impart clinically significant improvements in pain and delay progression of joint structural damage. Further work is required to determine the relative contributions of mechanical and metabolic factors in the pathogenesis of OA.

  19. Endocannabinoids and obesity.

    Science.gov (United States)

    Chen, Guoxun; Pang, Zhen

    2013-01-01

    A safe and effective antiobesity drug is needed to combat the global obesity epidemic. The discovery of cannabinoids from medicinal herbs has revealed the endocannabinoid system (ECS) in animals and humans, which regulates various physiological activities such as feeding, thermogenesis, and body weight (BW). Although cannabinoid receptors 1 (CB1) antagonists have shown antiobesity efficacies in animal models and in the clinic, they failed to establish as a treatment due to their psychological side effects. Recent studies indicate that CB1 in various peripheral tissues may mediate some of the therapeutic effects of CB1 antagonists, such as improved lipid and glucose homeostasis. It rationalizes the development of compounds with limited brain penetration, for minimizing the side effects while retaining the therapeutic efficacies. A survey of the literature has revealed some controversies about how the ECS affects obesity. This review summarizes the research progresses and discusses some future perspectives.

  20. 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...

  1. Childhood Obesity and the Right to Health

    DEFF Research Database (Denmark)

    Ó Cathaoir, Katharina Eva

    2016-01-01

    Childhood obesity is now a global health epidemic, yet the obligations of states to prevent obesity through fulfillment of the right to health have received limited consideration. This article examines the childhood obesity recommendations of the UN Committee on the Rights of the Child (the...... 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...

  2. Chronobiology and obesity

    Directory of Open Access Journals (Sweden)

    Marta Garaulet

    2013-09-01

    Full Text Available Chronobiology is a word derived from three Greek stems: kronos for time, bios for life and logos for study. From microarrays studies, now it is accepted that 10-30% of the human genome is under the control of circadian molecular clocks. This implies that most behavioral, physiological and biochemical variables display circadian rhythms in their expression. In its simplest form, circadian clocks are composed of a set of proteins that generate self-sustained circadian oscillations. The molecular clock comprises two transcription factors, CLOCK and BMAL1, whereas PERs and CRYs are responsible for the negative limb. One of the most important questions related to the circadian system and obesity, was to elucidate if adipose tissue displayed circadian rhythmicity or whether it had an internal peripheral clock. Our group of research has provided an overall view of the internal temporal order of circadian rhythms in human adipose tissue. A new concept related to illness is Chronodisruption (CD. It is defined as a relevant disturbance of the internal temporal order of physiological and behavioral circadian rhythms. In our modern society, CD may be common in several conditions such as jet lag, shift work, light at night, or social jet lag. In addition clock gene polymorphisms and aging may have also chronodisruptive effects. Our group has also demonstrated that Obesity and CD are also highly interconnected. With the help of chronobiology we can reach a new view of obesity considering not only "what" are the factors involved in obesity, but also "when" these factors are produced.

  3. Expressions of neuropeptide Y and Y1 receptor in subcutaneous and visceral fat tissues in normal weight and obese humans and their correlations with clinical parameters and peripheral metabolic factors.

    Science.gov (United States)

    Sitticharoon, Chantacha; Chatree, Saimai; Churintaraphan, Malika

    2013-08-10

    Recently, neuropeptide Y (NPY) and Y1 receptor (Y1R) were found to be expressed and synthesized in adipose tissue. This study aimed to compare NPY and Y1R mRNA expressions in subcutaneous and visceral fat tissues as well as serum NPY in normal weight and obese humans and their correlations with clinical parameters and peripheral metabolic factors. We demonstrated that NPY mRNA expression was higher in obese than in normal weight humans (ptissues and was significantly greater in visceral when compared with subcutaneous fat in overall (ptissue and was statistically greater in subcutaneous when compared to visceral adipose tissue in obese (ptissue was positively correlated with body weight (R=0.586), BMI (R=0.611), waist (R=0.474) and hip (R=0.483) circumferences, insulin levels (R=0.539), and HOMA-IR (R=0.480). As the result, Y1R expression in visceral adipose tissue might be an indicator of increased risk of metabolic syndrome. Further studies about blocking specific Y1R may propose strategies for risk reduction in metabolic syndrome and prevention or treatment of obesity.

  4. Oxazolone and ethanol induce colitis in non-obese diabetic-severe combined immunodeficiency interleukin-2Rγnull mice engrafted with human peripheral blood mononuclear cells

    Science.gov (United States)

    Nolte, T; Zadeh-Khorasani, M; Safarov, O; Rueff, F; Gülberg, V; Herbach, N; Wollenberg, A; Mueller, T; Siebeck, M; Wolf, E; Gropp, R

    2013-01-01

    Oxazolone-induced colitis in mice has become a recognized model to study the efficacy of therapeutics targeting the immunological response underlying the development of inflammatory bowel disease. However, this model cannot be used when therapeutics designed to address human targets do not interact with the respective murine counterpart. In this study, we examined the induction of oxazolone mediated colitis in non-obese diabetic-severe combined immunodeficiency interleukin-2Rγnull (NOD-SCID IL2Rγnull) mice engrafted with human peripheral blood mononuclear cells (hPBMC) derived from patients suffering from ulcerative colitis (UC), atopic dermatitis (AD) and healthy volunteers. NOD-SCID IL2Rγ null mice were engrafted with hPBMC followed by challenge with oxazolone or ethanol vehicle. Mice developed the same symptoms as observed previously in immunocompetent mice. The clinical activity score increased and the colon architecture was characterized by the development of oedema, fibrosis, crypt loss and dense infiltration of predominantly T cells into the lamina propria. Fluorescence activated cell sorter (FACS) analysis of lymphocytes in the colon identified natural killer (NK) T cells as a major constituent. In contrast to studies with immunocompetent mice, we observed the same phenotype in the group challenged with ethanol vehicle. The phenotype was most pronounced in mice engrafted with PBMC derived from a patient suffering from UC, suggesting that the immunological history of the donors predisposes the engrafted mice to react to ethanol. The model described here has the potential to study the efficacy of therapeutics targeting human lymphocytes in a model which is more reflective of the human disease. In addition, it might be developed to elucidate molecular mechanisms underlying the disease. PMID:23574330

  5. Determinants of obesity in transition economies: The case of Russia

    NARCIS (Netherlands)

    Rizov, M.I.; Huffman, S.K.

    2007-01-01

    This paper examines human obesity, measured as weight and body mass index (BMI), and its determinants in Russia. Obesity increased dramatically during transition from a planned to a market economy, by 38 percent. We determine the factors contributing to rising obesity using individual level data fro

  6. Obesity and Hispanic Americans

    Science.gov (United States)

    ... and Data > Minority Population Profiles > Hispanic/Latino > Obesity Obesity and Hispanic Americans Among Mexican American women, 77 ... ss6304.pdf [PDF | 3.38MB] HEALTH IMPACT OF OBESITY More than 80 percent of people with type ...

  7. Obesity Hypoventilation Syndrome

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Is Obesity Hypoventilation Syndrome? Obesity hypoventilation (HI-po-ven-tih- ... NHLBI Research Featured in HBO Documentary Series on Obesity Hear people talk about their challenges and successes ...

  8. Obesity and African Americans

    Science.gov (United States)

    ... Data > Minority Population Profiles > Black/African American > Obesity Obesity and African Americans African American women have the ... ss6304.pdf [PDF | 3.38MB] HEALTH IMPACT OF OBESITY More than 80 percent of people with type ...

  9. Obesity and Asian Americans

    Science.gov (United States)

    ... and Data > Minority Population Profiles > Asian American > Obesity Obesity and Asian Americans Non-Hispanic whites are 60% ... youthonline . [Accessed 05/25/2016] HEALTH IMPACT OF OBESITY More than 80 percent of people with type ...

  10. Childhood Obesity Facts

    Science.gov (United States)

    ... Breastfeeding Micronutrient Malnutrition State and Local Programs Childhood Obesity Facts Recommend on Facebook Tweet Share Compartir On ... Children (WIC) Program, 2000–2014 Prevalence of Childhood Obesity in the United States, 2011-2014 Childhood obesity ...

  11. COL18A1 is highly expressed during human adipocyte differentiation and the SNP c.1136C > T in its "frizzled" motif is associated with obesity in diabetes type 2 patients

    Directory of Open Access Journals (Sweden)

    Flavia I.V. Errera

    2008-03-01

    Full Text Available Collagen XVIII can generate two fragments, NC11-728 containing a frizzled motif which possibly acts in Wnt signaling and Endostatin, which is cleaved from the NC1 and is a potent inhibitor of angiogenesis. Collagen XVIII and Wnt signaling have recently been associated with adipogenic differentiation and obesity in some animal models, but not in humans. In the present report, we have shown that COL18A1 expression increases during human adipogenic differentiation. We also tested if polymorphisms in the Frizzled (c.1136C>T; Thr379Met and Endostatin (c.4349G>A; Asp1437Asn regions contribute towards susceptibility to obesity in patients with type 2 diabetes (113 obese, BMI =30; 232 non-obese, BMI A and obesity, but we observed a significantly higher frequency of homozygotes c.1136TT in obese (19.5% than in non-obese individuals (10.9% [P = 0.02; OR = 2.0 (95%CI: 1.07-3.73], suggesting that the allele c.1136T is associated to obesity in a recessive model. This genotype, after controlling for cholesterol, LDL cholesterol, and triglycerides, was independently associated with obesity (P = 0.048, and increases the chance of obesity in 2.8 times. Therefore, our data suggest the involvement of collagen XVIII in human adipogenesis and susceptibility to obesity.Colágeno XVIII pode gerar dois fragmentos, um correspondendo à região NC11-728 contendo o motivo ''frizzled'', o qual possivelmente atua na sinalização Wnt, e outro correspondendo a Endostatina, que é clivada a partir da região NC1 e é uma potente inibidora de angiogênese. Colágeno XVIII e a via de sinalização Wnt foram recentemente associados à diferenciação adipogênica e obesidade em alguns modelosanimais, porém ainda não em humanos. No presente trabalho, mostramos que os níveis de expressão gênica do COL18A1 aumentam durante o processo de diferenciação adipogênica em humanos. Também testamos se polimorfismos localizados no motivo ''Frizzled'' (c.1136C > T; Thr379Met e na

  12. Obesity Prevalence Maps

    Science.gov (United States)

    ... Breastfeeding Micronutrient Malnutrition State and Local Programs Adult Obesity Prevalence Maps Recommend on Facebook Tweet Share Compartir Obesity Prevalence in 2015 Varies Across States and Territories ...

  13. Periodontal innate immune mechanisms relevant to obesity.

    Science.gov (United States)

    Amar, S; Leeman, S

    2013-10-01

    Obesity affects over 35% of the adult population of the USA, and obesity-related illnesses have emerged as the leading cause of preventable death worldwide, according to the World Health Organization. Obesity's secondary morbidities include increased risk of cardiovascular disease, type II diabetes, and cancer, in addition to increased occurrence and severity of infections. Sedentary lifestyle and weight gain caused by consumption of a high-fat diet contribute to the development of obesity, with individuals having a body mass index (BMI) score > 30 being considered obese. Genetic models of obesity (ob/ob mice, db/db mice, and fa/fa rats) have been insufficient to study human obesity because of the overall lack of genetic causes for obesity in human populations. To date, the diet-induced obese (DIO) mouse model best serves research studies relevant to human health. Periodontal disease presents with a wide range of clinical variability and severity. Research in the past decade has shed substantial light on both the initiating infectious agents and host immunological responses in periodontal disease. Up to 46% of the general population harbors the microorganism(s) associated with periodontal disease, although many are able to limit the progression of periodontal disease or even clear the organism(s) if infected. In the last decade, several epidemiological studies have found an association between obesity and increased incidence of periodontal disease. This review focuses on exploring the immunological consequences of obesity that exacerbate effects of infection by pathogens, with focus on infection by the periodontal bacterium Porphyromonas gingivalis as a running example.

  14. Human monoclonal antibodies against glucagon receptor improve glucose homeostasis by suppression of hepatic glucose output in diet-induced obese mice.

    Directory of Open Access Journals (Sweden)

    Wook-Dong Kim

    Full Text Available AIM: Glucagon is an essential regulator of hepatic glucose production (HGP, which provides an alternative therapeutic target for managing type 2 diabetes with glucagon antagonists. We studied the effect of a novel human monoclonal antibody against glucagon receptor (GCGR, NPB112, on glucose homeostasis in diet-induced obese (DIO mice. METHODS: The glucose-lowering efficacy and safety of NPB112 were investigated in DIO mice with human GCGR for 11 weeks, and a hyperinsulinemic-euglycemic clamp study was conducted to measure HGP. RESULTS: Single intraperitoneal injection of NPB112 with 5 mg/kg effectively decreased blood glucose levels in DIO mice for 5 days. A significant reduction in blood glucose was observed in DIO mice treated with NPB112 at a dose ≥5 mg/kg for 6 weeks, and its glucose-lowering effect was dose-dependent. Long-term administration of NPB112 also caused a mild 29% elevation in glucagon level, which was returned to the normal range after discontinuation of treatment. The clamp study showed that DIO mice injected with NPB112 at 5 mg/kg were more insulin sensitive than control mice, indicating amelioration of insulin resistance by treatment with NPB112. DIO mice treated with NPB112 showed a significant improvement in the ability of insulin to suppress HGP, showing a 33% suppression (from 8.3 mg/kg/min to 5.6 mg/kg/min compared to the 2% suppression (from 9.8 mg/kg/min to 9.6 mg/kg/min in control mice. In addition, no hypoglycemia or adverse effect was observed during the treatment. CONCLUSIONS: A novel human monoclonal GCGR antibody, NPB112, effectively lowered the glucose level in diabetic animal models with mild and reversible hyperglucagonemia. Suppression of excess HGP with NPB112 may be a promising therapeutic modality for the treatment of type 2 diabetes.

  15. MAP3K8 (TPL2/COT) Affects Obesity-Induced Adipose Tissue Inflammation without Systemic Effects in Humans and in Mice

    NARCIS (Netherlands)

    Ballak, D.B.; Essen, P. van; Diepen, J.A. van; Jansen, H.J.; Hijmans, A.G.; Matsuguchi, T.; Sparrer, H.; Tack, C.J.J.; Netea, M.G.; Joosten, L.A.B.; Stienstra, R.

    2014-01-01

    Chronic low-grade inflammation in adipose tissue often accompanies obesity, leading to insulin resistance and increasing the risk for metabolic diseases. MAP3K8 (TPL2/COT) is an important signal transductor and activator of pro-inflammatory pathways that has been linked to obesity-induced adipose ti

  16. 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....

  17. 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."

  18. Childhood Obesity and the Right to Health

    DEFF Research Database (Denmark)

    Ó Cathaoir, Katharina Eva

    2016-01-01

    Childhood obesity is now a global health epidemic, yet the obligations of states to prevent obesity through fulfillment of the right to health have received limited consideration. This article examines the childhood obesity recommendations of the UN Committee on the Rights of the Child (the...... committee on the CRC), the Special Rapporteur on the right to health, and the UN High Commissioner on Human Rights. It suggests how their engagement might be strengthened. It concludes that the final report of the World Health Organization’s Commission on Ending Childhood Obesity could provide the committee...... 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...

  19. Central nervous system lipocalin-type prostaglandin D2-synthase is correlated with orexigenic neuropeptides, visceral adiposity and markers of the hypothalamic-pituitary-adrenal axis in obese humans.

    Science.gov (United States)

    Elias, E; Benrick, A; Behre, C J; Ekman, R; Zetterberg, H; Stenlöf, K; Wallenius, V

    2011-06-01

    Lipocalin-type prostaglandin D2-synthase (L-PGDS) is the main producer of prostaglandin D2 (PGD2) in the central nervous system (CNS). Animal data suggest effects of central nervous L-PGDS in the regulation of food intake and obesity. No human data are available. We hypothesised that a role for CNS L-PGDS in metabolic function in humans would be reflected by correlations with known orexigenic neuropeptides. Cerebrospinal fluid (CSF) and serum samples were retrieved from 26 subjects in a weight loss study, comprising a 3-week dietary lead-in followed by 12-weeks of leptin or placebo treatment. At baseline, CSF L-PGDS was positively correlated with neuropeptide Y (NPY) (ρ = 0.695, P obesity by interaction with the neuroendocrine circuits regulating appetite and fat distribution. Further interventional studies will be needed to characterise these interactions in more detail.

  20. 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

    2016-11-14

    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

  1. Rai1 haploinsufficiency causes reduced Bdnf expression resulting in hyperphagia, obesity and altered fat distribution in mice and humans with no evidence of metabolic syndrome.

    Science.gov (United States)

    Burns, Brooke; Schmidt, Kristie; Williams, Stephen R; Kim, Sun; Girirajan, Santhosh; Elsea, Sarah H

    2010-10-15

    Smith-Magenis syndrome (SMS) is a genetic disorder caused by haploinsufficiency of the retinoic acid induced 1 (RAI1) gene. In addition to intellectual disabilities, behavioral abnormalities and sleep disturbances, a majority of children with SMS also have significant early-onset obesity. To study the role of RAI1 in obesity, we investigated the growth and obesity phenotype in a mouse model haploinsufficient for Rai1. Data show that Rai1(+/-) mice are hyperphagic, have an impaired satiety response and have altered abdominal and subcutaneous fat distribution, with Rai1(+/-) female mice having a higher proportion of abdominal fat when compared with wild-type female mice. Expression analyses revealed that Bdnf (brain-derived neurotrophic factor), a gene previously associated with hyperphagia and obesity, is downregulated in the Rai1(+/-) mouse hypothalamus, and reporter studies show that RAI1 directly regulates the expression of BDNF. Even though the Rai1(+/-) mice are significantly obese, serum analyses do not reveal any evidence of metabolic syndrome. Supporting these findings, a caregiver survey revealed that even though a high incidence of abdominal obesity is observed in females with SMS, they did not exhibit a higher incidence of indicators of metabolic syndrome above the general population. We conclude that Rai1 haploinsufficiency represents a single-gene model of obesity with hyperphagia, abnormal fat distribution and altered hypothalamic gene expression associated with satiety, food intake, behavior and obesity. Linking RAI1 and BDNF provides a more thorough understanding of the role of Rai1 in growth and obesity and insight into the complex pathogenicity of obesity, behavior and sex-specific differences in adiposity.

  2. Experimental model to induce obesity in rats

    OpenAIRE

    von Diemen,Vinicius; Trindade, Eduardo Neubarth; Trindade, Manoel Roberto Maciel

    2006-01-01

    The etiology of obesity is multifactorial and is becoming a problem of public health, due to its increased prevalence and the consequent repercussion of its comorbidities on the health of the population. The great similarity and homology between the genomes of rodents and humans make these animal models a major tool to study conditions affecting humans, which can be simulated in rats. Obesity can be induced in animals by neuroendocrine, dietary or genetic changes. The most widely used models ...

  3. Paradoxical Effects of Fruit on Obesity

    Science.gov (United States)

    Sharma, Satya P.; Chung, Hea J.; Kim, Hyeon J.; Hong, Seong T.

    2016-01-01

    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. PMID:27754404

  4. 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.

  5. The chronobiology, etiology and pathophysiology of obesity.

    Science.gov (United States)

    Garaulet, M; Ordovás, J M; Madrid, J A

    2010-12-01

    The effect of CD on human health is an emerging issue. Many records link CD with diseases such as cancer, cardiovascular, cognitive impairment and obesity, all of them conducive to premature aging. The amount of sleep has declined by 1.5 h over the past century, accompanied by an important increase in obesity. Shift work, sleep deprivation and exposure to bright light at night increase the prevalence of adiposity. Animal models have shown that mice with Clock gene disruption are prone to developing obesity and MetS. This review summarizes the latest developments with regard to chronobiology and obesity, considering (1) how molecular clocks coordinate metabolism and the specific role of the adipocyte; (2) CD and its causes and pathological consequences; (3) the epidemiological evidence of obesity as a chronobiological illness; and (4) theories of circadian disruption and obesity. Energy intake and expenditure, relevance of sleep, fat intake from a circadian perspective and psychological and genetic aspects of obesity are examined. Finally, ideas about the use of chronobiology in the treatment of obesity are discussed. Such knowledge has the potential to become a valuable tool in the understanding of the relationship between the chronobiology, etiology and pathophysiology of obesity.

  6. The gut microbiota, obesity and insulin resistance.

    Science.gov (United States)

    Shen, Jian; Obin, Martin S; Zhao, Liping

    2013-02-01

    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 inflammation and insulin resistance. In this review we discuss molecular and cell biological mechanisms by which the microbiota participate in host functions that impact the development and maintenance of the obese state, including host ingestive behavior, energy harvest, energy expenditure and fat storage. We additionally explore the diverse signaling pathways that regulate gut permeability and bacterial translocation to the host and how these are altered in the obese state to promote the systemic inflammation ("metabolic endotoxemia") that is a hallmark of obesity and its complications. Fundamental to our discussions is the concept of "crosstalk", i.e., the biochemical exchange between host and microbiota that maintains the metabolic health of the superorganism and whose dysregulation is a hallmark of the obese state. Differences in community composition, functional genes and metabolic activities of the gut microbiota appear to distinguish lean vs obese individuals, suggesting that gut 'dysbiosis' contributes to the development of obesity and/or its complications. The current challenge is to determine the relative importance of obesity-associated compositional and functional changes in the microbiota and to identify the relevant taxa and functional gene modules that promote leanness and metabolic health. As diet appears to play a predominant role in shaping the microbiota and promoting obesity-associated dysbiosis, parallel initiatives are required to elucidate dietary patterns and diet components (e.g., prebiotics, probiotics) that promote healthy gut microbiota. How the microbiota promotes human health and disease is a rich area of investigation that is likely to generate

  7. Comparison of Markers and Functional Attributes of Human Adipose-Derived Stem Cells and Dedifferentiated Adipocyte Cells from Subcutaneous Fat of an Obese Diabetic Donor.

    Science.gov (United States)

    Watson, James E; Patel, Niketa A; Carter, Gay; Moor, Andrea; Patel, Rekha; Ghansah, Tomar; Mathur, Abhishek; Murr, Michel M; Bickford, Paula; Gould, Lisa J; Cooper, Denise R

    2014-03-01

    Objective: Adipose tissue is a robust source of adipose-derived stem cells (ADSCs) that may be able to provide secreted factors that promote the ability of wounded tissue to heal. However, adipocytes also have the potential to dedifferentiate in culture to cells with stem cell-like properties that may improve their behavior and functionality for certain applications. Approach: ADSCs are adult mesenchymal stem cells that are cultured from the stromal vascular fraction of adipose tissue. However, adipocytes are capable of dedifferentiating into cells with stem cell properties. In this case study, we compare ADSC and dedifferentiated fat (DFAT) cells from the same patient and fat depot for mesenchymal cell markers, embryonic stem cell markers, ability to differentiate to adipocytes and osteoblasts, senescence and telomerase levels, and ability of conditioned media (CM) to stimulate migration of human dermal fibroblasts (HDFs). Innovation and Conclusions: ADSCs and DFAT cells displayed identical levels of CD90, CD44, CD105, and were CD34- and CD45-negative. They also expressed similar levels of Oct4, BMI1, KLF4, and SALL4. DFAT cells, however, showed higher efficiency in adipogenic and osteogenic capacity. Telomerase levels of DFAT cells were double those of ADSCs, and senescence declined in DFAT cells. CM from both cell types altered the migration of fibroblasts. Despite reports of ADSCs from a number of human depots, there have been no comparisons of the ability of dedifferentiated DFAT cells from the same donor and depot to differentiate or modulate migration of HDFs. Since ADSCs were from an obese diabetic donor, reprogramming of DFAT cells may help improve a patient's cells for regenerative medicine applications.

  8. [Obesity and cancer].

    Science.gov (United States)

    Salaün, Hélène; Thariat, Juliette; Vignot, Marina; Merrouche, Yacine; Vignot, Stéphane

    2017-01-01

    The proportion of people affected by obesity is increasing and this finding emphasizes several issues in oncology: obesity as a risk factor for cancer, prognostic value of obesity in cancer patients, nutritional assessment in overweight patients and impact of obesity on treatment management. It is important to remember the common underevaluation of malnutrition in overweight or obese patients. Every caregiver must be especially careful about the management of comorbidities in these patients.

  9. 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....... The obese child has an increased risk of perioperative complications especially related to airway management and ventilation. There is a significantly increased risk of difficult mask ventilation and perioperative desaturation. Furthermore, obesity has an impact on the pharmacokinetics of most anesthetic...

  10. MicroRNA 21 regulates the proliferation of human adipose tissue-derived mesenchymal stem cells and high-fat diet-induced obesity alters microRNA 21 expression in white adipose tissues.

    Science.gov (United States)

    Kim, Yeon Jeong; Hwang, Soo Hyun; Cho, Hyun Hwa; Shin, Keun Koo; Bae, Yong Chan; Jung, Jin Sup

    2012-01-01

    A better understanding of the molecular mechanisms that govern human adipose tissue-derived mesenchymal stem cells (hASCs) differentiation could provide new insights into a number of diseases including obesity. Our previous study demonstrated that microRNA-21 (miR-21) controls the adipogenic differentiation of hASCs. In this study, we determined the expression of miR-21 in white adipose tissues in a high-fat diet (HFD)-induced obesity mouse model to examine the relationship between miR-21 and obesity and the effect of miR-21 on hASCs proliferation. Our study showed biphasic changes of miR-21 expression and a correlation between miR-21 level and adipocyte number in the epididymal fat of HFD mice. Over-expression of miR-21 decreased cell proliferation, whereas inhibiting miR-21 with 2'-O-methyl-antisense RNA increased it. Over-expression of miR-21 decreased both protein and mRNA levels of STAT3, whereas inhibiting miR-21 with 2'-O-methyl-antisense RNA increased these levels. The activity of a luciferase construct containing the miR-21 target site from the STAT3 3'UTR was lower in LV-miR21-infected hASCs than in LV-miLacZ infected cells. RNA interference-mediated down-regulation of STAT3 decreased cell proliferation without affecting adipogenic differentiation. These findings provide the evidence of the correlation between miR-21 level and adipocyte number in the white adipose tissue of HFD-induced obese mice, which provides new insights into the mechanisms of obesity.

  11. 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

  12. 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....

  13. Obesity-related hypertension: possible pathophysiological mechanisms.

    Science.gov (United States)

    Vaněčková, Ivana; Maletínská, Lenka; Behuliak, Michal; Nagelová, Veronika; Zicha, Josef; Kuneš, Jaroslav

    2014-12-01

    Hypertension is one of the major risk factors of cardiovascular diseases, but despite a century of clinical and basic research, the discrete etiology of this disease is still not fully understood. The same is true for obesity, which is recognized as a major global epidemic health problem nowadays. Obesity is associated with an increasing prevalence of the metabolic syndrome, a cluster of risk factors including hypertension, abdominal obesity, dyslipidemia, and hyperglycemia. Epidemiological studies have shown that excess weight gain predicts future development of hypertension, and the relationship between BMI and blood pressure (BP) appears to be almost linear in different populations. There is no doubt that obesity-related hypertension is a multifactorial and polygenic trait, and multiple potential pathogenetic mechanisms probably contribute to the development of higher BP in obese humans. These include hyperinsulinemia, activation of the renin-angiotensin-aldosterone system, sympathetic nervous system stimulation, abnormal levels of certain adipokines such as leptin, or cytokines acting at the vascular endothelial level. Moreover, some genetic and epigenetic mechanisms are also in play. Although the full manifestation of both hypertension and obesity occurs predominantly in adulthood, their roots can be traced back to early ontogeny. The detailed knowledge of alterations occurring in the organism of experimental animals during particular critical periods (developmental windows) could help to solve this phenomenon in humans and might facilitate the age-specific prevention of human obesity-related hypertension. In addition, better understanding of particular pathophysiological mechanisms might be useful in so-called personalized medicine.

  14. 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.......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....

  15. Ethanol extract of lotus (Nelumbo nucifera) root exhibits an anti-adipogenic effect in human pre-adipocytes and anti-obesity and anti-oxidant effects in rats fed a high-fat diet.

    Science.gov (United States)

    You, Jeong Soon; Lee, Yun Ju; Kim, Kyoung Soo; Kim, Sung Hoon; Chang, Kyung Ja

    2014-03-01

    Lotus (Nelumbo Nucifera) root, a well-known medicinal plant in Asia, is reported to have various therapeutic benefits, including anti-diabetes, anti-hypertension, and anti-hyperlipidaemia. We hypothesized that the ethanol extract of lotus root (ELR) would exhibit an anti-adipogenic effect in human pre-adipocytes as well as anti-obesity and anti-oxidant effects in rats fed a high-fat diet. Treatment with ELR in human pre-adipocytes resulted in inhibition of lipid accumulation and attenuated expression of adipogenic transcription factors such as peroxisome proliferator-activated receptor gamma and adipocyte marker genes, such as glucose transporter 4 and leptin. Administration of ELR resulted in a significant decrease in relative weights of adipose tissues in rats fed a high-fat diet. Consumption of a high-fat diet resulted in an increase in serum total cholesterol (TC) and triglyceride (TG) levels; however, administration of ELR resulted in a decrease in the levels of TC and TG. Administration of ELR resulted in a decrease in the level of serum leptin and insulin. Administration of ELR in rats fed a high-fat diet resulted in a decrease in hepatic thiobarbituric acid reactive substance content, elevated by a high-fat diet and an increase in superoxide dismutase activity and hepatic glutathione content. These results suggest that lotus root exerts anti-oxidant and anti-obesity effects and could be used as a functional and nutraceutical ingredient in combatting obesity-related diseases.

  16. 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.

  17. Targeting microRNAs in obesity.

    Science.gov (United States)

    Xie, Huangming; Sun, Lei; Lodish, Harvey F

    2009-10-01

    Obesity is a serious health problem worldwide associated with an increased risk of life-threatening diseases such as type 2 diabetes, atherosclerosis, and certain types of cancer. Fundamental for the development of novel therapeutics for obesity and its associated metabolic syndromes is an understanding of the regulation of fat cell development. Recent computational and experimental studies have shown that microRNAs (miRNAs) play a role in metabolic tissue development, lipid metabolism and glucose homeostasis. In addition, many miRNAs are dysregulated in metabolic tissues from obese animals and humans, which potentially contributes to the pathogenesis of obesity-associated complications. In this review we summarize the current state of understanding of the roles of miRNAs in metabolic tissues under normal development and obese conditions, and discuss the potential use of miRNAs as therapeutic targets.

  18. Increased aldosterone: mechanism of hypertension in obesity.

    Science.gov (United States)

    Flynn, Colleen

    2014-05-01

    The prevalence of both obesity and hypertension are increasing worldwide. Hypertension is a common consequence of obesity. Increased central adiposity is associated with increased aldosterone levels and blood pressure in human beings. A number of small studies have shown an association between obesity-mediated hypertension and mechanisms directly linked to increased levels of aldosterone. These studies have shown a trend toward relatively greater blood pressure reduction using aldosterone-receptor blockers compared with other classes of antihypertensive agents. Other than treatment for weight loss, treatment of hypertension with specific antihypertensive medications that block or reduce aldosterone action are appropriate in obese patients. Further research is needed to understand the exact role of the adipocyte in obesity-mediated hypertension.

  19. Genetic polymorphisms of human β-adrenergic receptor genes and their association with obesity%人类β-肾上腺素受体基因的遗传多态性及其与肥胖的关系

    Institute of Scientific and Technical Information of China (English)

    刘昭前; 莫玮; 黄琼; 周宏灏

    2007-01-01

    The prevalent rates of overweight and obesity are steadily increasing all over the world. Previous studies of some candidate genes have indicated that most of the genes are associated with obesity in human adipose tissue. As much as 40% of the variations in body mass could be attributed to genetic difference. The β-adrenergic receptor (β-AR) plays a major role in the regulation of energy balance in humans. A high sympathetic nervous system activity has been shown to be associated with obesity and is believed to have pathogenetic relevance. Several common single nucleotide polymorphisms (SNPs) including Gly389Arg in β1-AR, Gln27Glu in β2-AR, and Trp64Arg in β3-AR in humans could alter receptor function and these variations ofβ-ARs were shown to have certain association with obesity. Here we summarize the genetic polymorphisms of human β-ARs and their potential impacts to obesity.%在世界范围内,肥胖和超重的发生率正在稳步增长.过去有关候选基因的大量研究已经表明,大多数基因与人类脂肪组织中肥胖的发生相关.与人体体质量相关的40%以上的基因变异可以产生遗传差异.β-肾上腺素受体在人体能量平衡调节中扮演重要作用,交感神经系统的高度激活被认为与肥胖的发生密切相关.β-肾上腺素受体的单核苷酸多态性如β1-肾上腺素受体Gly389Arg,β2-肾上腺素受体Gln27Glu和β3-肾上腺素受体Trp64Arg已经被证明能够改变受体的功能,并与肥胖的发生有关.本文就β-肾上腺素受体的遗传多态性以及它们在肥胖发生中的作用作一综述.

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

    OpenAIRE

    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 short-term but poor long-term results. New strategies are needed. A novel theory posits that obesity in pets and children is due to ‘treats’ and excessive meal amounts given by the ‘pet–parent’ and...

  1. Ghrelin in obesity, physiological and pharmacological considerations.

    Science.gov (United States)

    Álvarez-Castro, Paula; Pena, Lara; Cordido, Fernando

    2013-04-01

    The aim of this review is to summarize the physiological and pharmacological aspects of ghrelin. Obesity can be defined as an excess of body fat and is associated with significant disturbances in metabolic and endocrine function. Obesity has become a worldwide epidemic. In obesity there is a decreased growth hormone (GH) secretion, and the altered somatotroph secretion in obesity is functional. Ghrelin is a peptide that has a unique structure with 28 amino-acids and an n-octanoyl ester at its third serine residue, which is essential for its potent stimulatory activity on somatotroph secretion. The pathophysiological mechanism responsible for GH hyposecretion in obesity is probably multifactorial, and there is probably a defect in ghrelin secretion. Ghrelin is the only known circulating orexigenic factor, and has been found to be reduced in obese humans. Ghrelin levels in blood decrease during periods of feeding. Due to its orexigenic and metabolic effects, ghrelin has a potential benefit in antagonizing protein breakdown and weight loss in catabolic conditions such as cancer cachexia, renal and cardiac disease, and age-related frailty. Theoretically ghrelin receptor antagonists could be employed as anti-obesity drugs, blocking the orexigenic signal. By blocking the constitutive receptor activity, inverse agonists of the ghrelin receptor may lower the set-point for hunger, and could be used for the treatment of obesity. In summary, ghrelin secretion is reduced in obesity, and could be partly responsible for GH hyposecretion in obesity, ghrelin antagonist or partial inverse agonists should be considered for the treatment of obesity.

  2. [The obesity paradox].

    Science.gov (United States)

    Du Pan, Rémi C Martin; Golay, Alain

    2014-06-25

    In general population, cardiovascular (CV) mortality increases in parallel with obesity severity, determined by body mass index (BMI). However in cohorts of patients with coronary diseases or heart failure a decrease of the global mortality has been observed in patients aged more than 65 years old with moderate obesity (BMI = 30-35) compared to normal weight people (BMI = 20-25) and morbid obese (BMI > 35). This "obesity paradox" could result from the selection of obese people with healthy metabolic profile and way of life. BMI does not allow to distinguish lean body mass from fat mass and therefore to evaluate abdominal obesity which is associated with metabolic syndrome and CV risk.

  3. 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....

  4. Obesity in Infants to Preschoolers

    Science.gov (United States)

    ... is childhood obesity? Overweight in Children BMI in Children Is Childhood Obesity an Issue in Your Home? Addressing your Child's Weight at the Doctor Preventing Childhood Obesity: Tips for Parents and Caretakers Obesity in Infants ...

  5. Impact of infant feeding practices on childhood obesity.

    Science.gov (United States)

    Butte, Nancy F

    2009-02-01

    Childhood obesity is a complex disease influenced by genetic and environmental factors and their interactions. The current surge in childhood obesity in the United States is attributable to an interaction between a genetic predisposition toward obesity and a permissive environment. Several recent systematic reviews and meta-analyses have been published on the association between breast-feeding and childhood obesity. In these analyses, adjustment for confounding factors attenuated or nullified the protective effect of breast-feeding on later obesity. The Viva La Familia Study was designed to identify genetic and environmental factors affecting obesity and its comorbidities in 1030 Hispanic children from 319 families. Odds ratios for potential risk factors associated with childhood overweight were computed using binary logistic regression for panel data. Early infant-feeding practices were not significant. Salient independent risk factors for childhood obesity in this cohort of Hispanic children were age, birth weight, maternal obesity, paternal obesity, number of children in the family, and the percentage of awake time spent in sedentary activity. Breast-feeding may have a small protective effect against childhood obesity, although residual confounding may exist. Human milk is exquisitely fitted for optimal infant growth and development and may uniquely modulate neuroendocrine and immunologic pathways involved in the regulation of body weight. Nevertheless, other genetic and environmental determinants such as socioeconomic status, parental obesity, smoking, birth weight, and rapid infancy weight gain far supersede infant-feeding practices as risk factors for childhood obesity.

  6. 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

  7. 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.

  8. 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.

  9. Reducing Childhood Obesity

    Science.gov (United States)

    ... the NHLBI Obesity Education Initiative. (See accompanying article, " Obesity Research: A New Approach. ") We Can! focuses on three important behaviors: improved food choices, increased physical activity, and reduced recreational screen time. ...

  10. 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.

  11. 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.

  12. 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 ...

  13. Obesity and Anesthesia

    Science.gov (United States)

    ... Apnea and Anesthesia Smoking and Anesthesia Outpatient Surgery Obesity and Anesthesia More than one-third of Americans ... Sleep Apnea, a chronic medical problem common with obesity, can present with serious breathing problems before, during, ...

  14. Overweight and Obesity Statistics

    Science.gov (United States)

    ... the full list of resources ​​. Overweight and Obesity Statistics Page Content About Overweight and Obesity Prevalence of ... adults age 20 and older [ Top ] Physical Activity Statistics Adults Research Findings Research suggests that staying active ...

  15. Neuropeptides and obesity.

    Science.gov (United States)

    Beck, B

    2000-10-01

    neuromodulators include numerous brain areas, but some interest has returned to the classic ones such as the ventromedial and lateral hypothalamic areas because of the recent discovery of some peptides (orexins and melanin-concentrating hormone for the lateral hypothalamus) and receptors (CRF type 2 in the ventromedial hypothalamus). All of these pathways are redundant and function in a coordinated manner and sometimes by the novel expression of a peptide in an unusual area. The importance of such a phenomenon in obesity remains to be determined. Even if single-gene mutations are exceptions in human obesity, the study of genetic animal models of obesity has greatly contributed to the understanding of the regulation of feeding behavior and will allow researchers to develop new drug treatments for obesity that have to be associated with drastic changes in lifestyle (feeding, work habits, and physical activity) for a complete efficiency.

  16. 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

  17. Obesity-Related Hypertension

    OpenAIRE

    Re, Richard N.

    2009-01-01

    Obesity-associated arterial hypertension is characterized by activation of the sympathetic nervous system, activation of the renin-angiotensin system, and sodium retention, among other abnormalities. In this review, the following 3 facets of the obesity/hypertension nexus will be discussed: the potential mechanisms by which obesity can lead to elevated arterial pressure, the interaction of obesity with the sequelae of hypertension, and the therapies that are believed to optimally treat obesit...

  18. Leptin receptor 170 kDa (OB-R170) protein expression is reduced in obese human skeletal muscle: a potential mechanism of leptin resistance

    DEFF Research Database (Denmark)

    Fuentes, T; Ara, I; Guadalupe-Grau, A

    2010-01-01

    To examine whether obesity-associated leptin resistance could be due to down-regulation of leptin receptors (OB-Rs) and/or up-regulation of suppressor of cytokine signalling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) in skeletal muscle, which blunt janus kinase 2-dependent leptin...... had a greater amount of leptin receptors than the vastus lateralis, whilst SOCS3 protein expression was increased and basal STAT3, AMPKalpha and ACCbeta phosphorylation levels were reduced in the vastus lateralis compared with the deltoid muscle (all P leptin...... receptors and leptin signalling are reduced in obesity, particularly in the leg muscles....

  19. 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

  20. 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....

  1. Obesity, Physical Activity - Children.

    Science.gov (United States)

    Gilliam, Thomas B.

    Childhood obesity starts at a very early age, and preventive measures taken early enough may retard the development of fat cells. It appears that physical activity plays an important role in reducing obesity. The activity program must start early, in preschool days. It is felt that screening children for obesity when they first enter school and…

  2. 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…

  3. Obesity and respiratory diseases

    Directory of Open Access Journals (Sweden)

    Christopher Zammit

    2010-10-01

    Full Text Available Christopher Zammit, Helen Liddicoat, Ian Moonsie, Himender MakkerSleep and Ventilation Unit, Department of Respiratory Medicine, North Middlesex University Hospital, London, UKAbstract: The obesity epidemic is a global problem, which is set to increase over time. However, the effects of obesity on the respiratory system are often underappreciated. In this review, we will discuss the mechanical effects of obesity on lung physiology and the function of adipose tissue as an endocrine organ producing systemic inflammation and effecting central respiratory control. Obesity plays a key role in the development of obstructive sleep apnea and obesity hypoventilation syndrome. Asthma is more common and often harder to treat in the obese population, and in this study, we review the effects of obesity on airway inflammation and respiratory mechanics. We also discuss the compounding effects of obesity on chronic obstructive pulmonary disease (COPD and the paradoxical interaction of body mass index and COPD severity. Many practical challenges exist in caring for obese patients, and we highlight the complications faced by patients undergoing surgical procedures, especially given the increased use of bariatric surgery. Ultimately, a greater understanding of the effects of obesity on the respiratory disease and the provision of adequate health care resources is vital in order to care for this increasingly important patient population.Keywords: obesity, lung function, obstructive sleep apnea, obesity hypoventilation syndrome, anesthesia

  4. 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...

  5. The Complexity of Obesity

    Science.gov (United States)

    Gray, Katti

    2010-01-01

    With Americans fatter and more malnourished than ever--almost two-thirds of the population is considered overweight or obese compared with 56 percent in the late 1980s and early 1990s, and people of color and the poor are the most obese of all--federal and university researchers and outreach workers from various anti-obesity organizations aim to…

  6. Obesity and renal hemodynamics

    NARCIS (Netherlands)

    Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.

    2006-01-01

    Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile inde

  7. Effects of obesity, diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue: in vivo and in vitro studies

    Science.gov (United States)

    Kurdiova, Timea; Balaz, Miroslav; Vician, Marek; Maderova, Denisa; Vlcek, Miroslav; Valkovic, Ladislav; Srbecky, Miroslav; Imrich, Richard; Kyselovicova, Olga; Belan, Vitazoslav; Jelok, Ivan; Wolfrum, Christian; Klimes, Iwar; Krssak, Martin; Zemkova, Erika; Gasperikova, Daniela; Ukropec, Jozef; Ukropcova, Barbara

    2014-01-01

    Irisin was identified as a myokine secreted by contracting skeletal muscle, possibly mediating some exercise health benefits via ‘browning’ of white adipose tissue. However, a controversy exists concerning irisin origin, regulation and function in humans. Thus, we have explored Fndc5 gene and irisin protein in two clinical studies: (i) a cross-sectional study (effects of type 2 diabetes (T2D) in drug-naive men) and (ii) an intervention study (exercise effects in sedentary, overweight/obese individuals). Glucose tolerance and insulin sensitivity were assessed. Maximal aerobic capacity and muscle strength were measured before and after training. Body composition (magnetic resonance imaging), muscle and liver fat content (1H-magnetic resonance spectroscopy (MRS)) and in vivo muscle metabolism (32P-MRS) were determined. Skeletal muscle and subcutaneous abdominal adipose tissue samples were taken in the fasted state and during euglycaemic hyperinsulinaemia (adipose tissue) and before/after exercise training (muscle). We found that muscle Fndc5 mRNA was increased in prediabetes but not T2D. Fndc5 in adipose tissue and irisin in plasma were reduced in T2D by 40% and 50%, respectively. In contrast, T2D-derived myotubes expressed/secreted the highest levels of Fndc5/irisin. Neither hyperinsulinaemia (adipose tissue/plasma) nor exercise (muscle/plasma) affected Fndc5/irisin in vivo. Circulating irisin was positively associated with muscle mass, strength and metabolism and negatively with fasting glycaemia. Glucose and palmitate decreased Fndc5 mRNA in myotubes in vitro. We conclude that distinct patterns of Fndc5/irisin in muscle, adipose tissue and circulation, and concordant in vivo down-regulation in T2D, indicate that irisin might distinguish metabolic health and disease. Moreover, Fndc5/irisin was discordantly regulated in diabetic muscle and myotubes in vitro, suggesting that whole body factors, such as glucose and fatty acids, might be important for irisin

  8. Neuroendocrine perturbations in human obesity

    NARCIS (Netherlands)

    Kok, Petra

    2006-01-01

    The evolutionary advantage to conserve energy in the form of adipose issue in order to survive long periods of food shortage in the past, turned into a major health problem in current times of plenty. Excess accumulation of body fat, or “obesity”, is associated with severely increased co-morbidity a

  9. 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.

  10. 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.

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

    Science.gov (United States)

    Leon-Cabrera, Sonia; Arana-Lechuga, Yoaly; Esqueda-León, Enrique; Terán-Pérez, Guadalupe; Gonzalez-Chavez, Antonio; Velázquez Moctezuma, Javier

    2015-01-01

    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. PMID:25944984

  12. 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

    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......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...... 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...

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

    Directory of Open Access Journals (Sweden)

    Camilla Scheele

    Full Text Available Obesity and type 2 diabetes are associated with chronically elevated systemic levels of IL-6, a pro-inflammatory cytokine with a role in skeletal muscle metabolism that signals through the IL-6 receptor (IL-6Rα. We hypothesized that skeletal muscle in obesity-associated type 2 diabetes develops 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 isolated satellite cells from skeletal muscle of people that were healthy (He, obese (Ob or were obese and had type 2 diabetes (DM, and differentiated them in vitro into myocytes. Down-regulation of IL-6Rα was conserved in Ob myocytes. In addition, acute IL-6 administration for 30, 60 and 120 minutes, resulted in a down-regulation of IL-6Rα protein in Ob myocytes compared to both He myocytes (P<0.05 and DM myocytes (P<0.05. Interestingly, there was a strong time-dependent regulation of IL-6Rα protein in response to IL-6 (P<0.001 in He myocytes, not present in the other groups. Assessing downstream signaling, DM, but not Ob myocytes demonstrated a trend towards an increased protein phosphorylation of STAT3 in DM myocytes (P = 0.067 accompanied by a reduced SOCS3 protein induction (P<0.05, in response to IL-6 administration. Despite this loss of negative control, IL-6 failed to increase AMPKα2 activity and IL-6 mRNA expression in DM myocytes. There was no difference in fusion capacity of myocytes between cell groups. Our data suggest that negative control of IL-6 signaling is increased in myocytes in obesity, whereas a dysfunctional IL-6 signaling is established further downstream of IL-6Rα in DM myocytes, possibly representing a novel mechanism by which skeletal muscle function is compromised in type 2 diabetes.

  14. Obesity and cancer: mechanistic insights from transdisciplinary studies.

    Science.gov (United States)

    Allott, Emma H; Hursting, Stephen D

    2015-12-01

    Obesity is associated with a range of health outcomes that are of clinical and public health significance, including cancer. Herein, we summarize epidemiologic and preclinical evidence for an association between obesity and increased risk of breast and prostate cancer incidence and mortality. Moreover, we describe data from observational studies of weight change in humans and from calorie-restriction studies in mouse models that support a potential role for weight loss in counteracting tumor-promoting properties of obesity in breast and prostate cancers. Given that weight loss is challenging to achieve and maintain, we also consider evidence linking treatments for obesity-associated co-morbidities, including metformin, statins and non-steroidal anti-inflammatory drugs, with reduced breast and prostate cancer incidence and mortality. Finally, we highlight several challenges that should be considered when conducting epidemiologic and preclinical research in the area of obesity and cancer, including the measurement of obesity in population-based studies, the timing of obesity and weight change in relation to tumor latency and cancer diagnosis, and the heterogeneous nature of obesity and its associated co-morbidities. Given that obesity is a complex trait, comprised of behavioral, epidemiologic and molecular/metabolic factors, we argue that a transdisciplinary approach is the key to understanding the mechanisms linking obesity and cancer. As such, this review highlights the critical need to integrate evidence from both epidemiologic and preclinical studies to gain insight into both biologic and non-biologic mechanisms contributing to the obesity-cancer link.

  15. Asthma and obesity: a known association but unknown mechanism.

    Science.gov (United States)

    Farah, Claude S; Salome, Cheryl M

    2012-04-01

    The obese asthma phenotype is an increasingly common encounter in our clinical practice. Epidemiological data indicate that obesity increases the prevalence and incidence of asthma, and evidence that obesity precedes the development of asthma raises the possibility of a causal association. Obese patients with asthma experience more symptoms and increased morbidity compared with non-obese asthma patients. Despite more than a decade of research into this association, the exact mechanisms that underlie the interaction of obesity with asthma remain unclear. It is unlikely that the asthma-obesity association is simply due to comorbidities such as obstructive sleep apnoea or gastroesophageal reflux disease. Although inflammatory pathways are purported to play a role, there is scant direct evidence in humans that systemic inflammation modulates the behaviour of the asthmatic airway or the expression of symptoms in the obese. The role of non-eosinophilic airway inflammation also requires further study. Obesity results in important changes to the mechanical properties of the respiratory system, and these obesity-related factors appear to exert an additive effect to the asthma-related changes seen in the airways. An understanding of the various physiological perturbations that might be contributing to symptoms in obese patients with asthma will allow for a more targeted and rational treatment approach for these patients.

  16. Developmental origins of obesity: programmed adipogenesis.

    Science.gov (United States)

    Desai, Mina; Beall, Marie; Ross, Michael G

    2013-02-01

    The metabolic syndrome epidemic, including a marked increase in the prevalence of obesity and gestational diabetes mellitus (GDM) among pregnant women, represents a significant public health problem. There is increasing recognition that the risk of adult obesity is clearly influenced by prenatal and infant environmental exposures, particularly nutrition. This tenet is the fundamental basis of developmental programming. Low birth weight, together with infant catch-up growth, is associated with a significant risk of adult obesity. Exposure to maternal obesity, with or without GDM, or having a high birth weight also represents an increased risk for childhood and adult obesity. Animal models have replicated human epidemiologic findings and elucidated potential programming mechanisms that include altered organ development, cellular signaling responses, and epigenetic modifications. Prenatal care has made great strides in optimizing maternal, fetal, and neonatal health, and now has the opportunity to begin interventions which prevent or reduce childhood/adult obesity. Guidelines that integrate optimal pregnancy nutrition and weight gain, management of GDM, and newborn feeding strategies with long-term consequences on adult obesity, remain to be elucidated.

  17. 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.

  18. Obesity and hypertension

    Science.gov (United States)

    Jiang, Shu-Zhong; Lu, Wen; Zong, Xue-Feng; Ruan, Hong-Yun; Liu, Yi

    2016-01-01

    The imbalance between energy intake and expenditure is the main cause of excessive overweight and obesity. Technically, obesity is defined as the abnormal accumulation of ≥20% of body fat, over the individual's ideal body weight. The latter constitutes the maximal healthful value for an individual that is calculated based chiefly on the height, age, build and degree of muscular development. However, obesity is diagnosed by measuring the weight in relation to the height of an individual, thereby determining or calculating the body mass index. The National Institutes of Health have defined 30 kg/m2 as the limit over which an individual is qualified as obese. Accordingly, the prevalence of obesity in on the increase in children and adults worldwide, despite World Health Organization warnings. The growth of obesity and the scale of associated health issues induce serious consequences for individuals and governmental health systems. Excessive overweight remains among the most neglected public health issues worldwide, while obesity is associated with increasing risks of disability, illness and death. Cardiovascular diseases, the leading cause of mortality worldwide, particularly hypertension and diabetes, are the main illnesses associated with obesity. Nevertheless, the mechanisms underlying obesity-associated hypertension or other associated metabolic diseases remains to be adequately investigated. In the present review, we addressed the association between obesity and cardiovascular disease, particularly the biological mechanisms linking obesity and hypertension. PMID:27703502

  19. Linking obesity and asthma.

    Science.gov (United States)

    Sutherland, E Rand

    2014-04-01

    A growing body of literature suggests that obesity has a significant impact on asthma risk, phenotype, and prognosis. Epidemiological studies have clearly demonstrated that asthma is more likely to occur in obese patients, and health status is impaired in obese individuals with asthma, with obese asthmatics experiencing more symptoms, worse quality of life, increased healthcare use, and increased asthma severity. However, obesity has well-described effects on lung function and mechanics that can lead to symptoms of dyspnea without causing the pathophysiologic changes of asthma. Adding to the challenges of evaluating this association, some studies have failed to demonstrate a robust relationship between obesity and traditional biomarkers of airway inflammation in adult asthmatics, leading to the conclusion that obesity does not necessarily worsen airway inflammation in asthma. In this regard, emerging data suggest that nonatopic mechanisms may be relevant in obese asthmatics, and that these mechanisms may have a direct impact on the response of obese asthmatics to asthma therapies, most notably inhaled glucocorticoids. This article will review selected aspects of the contributions of obesity-related airway and systemic inflammation to asthma, with a focus on the impact of obesity as a modifier of risk, prognosis, and therapeutic response in asthma.

  20. Challenges in obesity research

    Directory of Open Access Journals (Sweden)

    Andreu Palou

    2013-09-01

    Full Text Available Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors -often interrelated and many of them still unknown or poorly understood- can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity.

  1. Challenges in obesity research.

    Science.gov (United States)

    Palou, Andreu; Bonet, M Luisa

    2013-09-01

    Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors--often interrelated and many of them still unknown or poorly understood--can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity.

  2. Obesity and Gastrointestinal Diseases

    Directory of Open Access Journals (Sweden)

    Ai Fujimoto

    2013-01-01

    Full Text Available The prevalence of obesity in the Japanese population has been increasing dramatically in step with the Westernization of lifestyles and food ways. Our study demonstrated significant associations between obesity and a number of gastrointestinal disorders in a large sample population in Japan. We demonstrated that reflux esophagitis and hiatal hernia were strongly related to obesity (BMI > 25 in the Japanese. In particular, obesity with young male was a high risk for these diseases. On the other hand, it has been reported that obesity is also associated with Barrett’s esophagus and colorectal adenoma; however, obesity was not a risk factor for these diseases in our study. The difference of ethnicity of our subjects may partly explain why we found no data to implicate obesity as a risk factor for Barrett’s esophagus. Arterial sclerosis associated with advanced age and hyperglycemia was accompanied by an increased risk of colorectal adenoma.

  3. OPEN about obesity

    DEFF Research Database (Denmark)

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

    2007-01-01

    OBJECTIVE: Obesity-related under-reporting of usual dietary intake is one of the most persistent sources of bias in nutrition research. The aim of this paper is to characterize obese and non-obese individuals with respect to reporting errors observed with two common dietary instruments, using...... energy and protein recovery biomarkers as reference measures. POPULATION AND METHODS: This report employs data from the Observing Protein and Energy Nutrition (OPEN) study. Analyses are based on stratified samples of 211 (57 obese) men and 179 (50 obese) women who completed 24-h recalls (24HR), food...... 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...

  4. Association of the Intestinal Microbiota and Obesity.

    Science.gov (United States)

    López-Cepero, Andrea A; Palacios, Cristina

    2015-06-01

    Obesity is a condition mainly caused by an alteration in energy intake, shifting towards positive energy balance, which can be influenced by genetic and environmental factors. The human gut is heavily populated with microbial organisms. Recent evidence suggests that obesity is influenced by specific bacterial phyla present in the human gut that have increased energy harvesting capabilities. The main objective of this review is to identify the microbial taxa that are related to obesity and weight loss. In this review, we also discuss the differences between the phylum ratio of the gut microbiota population of obese individuals and that of individuals who have healthy weight. It has been shown that obese individuals have a higher ratio of Firmicutes to Bacteroidetes than healthy weight individuals. The few studies to date have shown that weight-loss treatment may change microbial population of the gut, as there is a decrease in the ratio of Firmicutes to Bacteroidetes. Treating imbalances of the gut microbiota may offer new possibilities for treating obesity.

  5. Obesity and respiratory diseases.

    Science.gov (United States)

    Zammit, Christopher; Liddicoat, Helen; Moonsie, Ian; Makker, Himender

    2010-10-20

    The obesity epidemic is a global problem, which is set to increase over time. However, the effects of obesity on the respiratory system are often underappreciated. In this review, we will discuss the mechanical effects of obesity on lung physiology and the function of adipose tissue as an endocrine organ producing systemic inflammation and effecting central respiratory control. Obesity plays a key role in the development of obstructive sleep apnea and obesity hypoventilation syndrome. Asthma is more common and often harder to treat in the obese population, and in this study, we review the effects of obesity on airway inflammation and respiratory mechanics. We also discuss the compounding effects of obesity on chronic obstructive pulmonary disease (COPD) and the paradoxical interaction of body mass index and COPD severity. Many practical challenges exist in caring for obese patients, and we highlight the complications faced by patients undergoing surgical procedures, especially given the increased use of bariatric surgery. Ultimately, a greater understanding of the effects of obesity on the respiratory disease and the provision of adequate health care resources is vital in order to care for this increasingly important patient population.

  6. Asthma and obesity.

    Science.gov (United States)

    Boulet, L-P

    2013-01-01

    The prevalence and incidence of asthma have increased among obese children and adults, particularly among women. Obesity seems to be a predisposing factor for the development of asthma, but the underlying mechanisms of its influence are still uncertain. Various hypotheses have been proposed to explain the link between obesity and asthma such as a common genetic predisposition, developmental changes, altered lung mechanics, the presence of a systemic inflammatory process, and an increased prevalence of associated comorbid conditions. Over-diagnosis of asthma does not seem to be more frequent in obese compared to non-obese subjects, but the added effects of obesity on respiratory symptoms can affect asthma control assessment. Obesity can make asthma more difficult to control and is associated with a reduced beneficial effect of asthma medications. This could be due to a change in asthma phenotype, particularly evidenced as a less eosinophilic type of airway inflammation combined to the added effects of changes in lung mechanics. Weight loss is associated with a universal improvement of asthma and should be part of asthma management in the obese patient. Additional research should be conducted to better determine how obesity influences the development and clinical expression of asthma, establish the optimal management of asthma in this population and determine how obesity affects long-term asthma outcomes in these patients.

  7. Obesity and asthma.

    Science.gov (United States)

    Gibson, Peter G

    2013-12-01

    There is a global epidemic of asthma and obesity that is concentrated in Westernized and developed countries. A causal association in some people with asthma is suggested by observations that obesity precedes the onset of asthma and that bariatric surgery for morbid obesity can resolve asthma. The obese asthma phenotype features poor asthma control, limited response to corticosteroids, and an exaggeration of the physiological effects of obesity on lung function, which includes a reduction in expiratory reserve volume and airway closure occurring during tidal breathing. Obesity has important implications for asthma treatment. Increasing corticosteroid doses based on poor asthma control, as currently recommended in guidelines, may lead to overtreatment with corticosteroids in obese asthma. Enhanced bronchodilation, particularly of the small airways, may reduce the component of airway closure due to increased bronchomotor tone and suggests that greater emphasis should be placed on long-acting bronchodilators in obese asthma. The societal implications of this are important: with increasing obesity there will be increasing asthma from obesity, and the need to identify successful individual and societal weight-control strategies becomes a key goal.

  8. Applications of Systems Genetics and Biology for Obesity Using Pig Models

    DEFF Research Database (Denmark)

    Kogelman, Lisette J. A.; Kadarmideen, Haja N.

    2016-01-01

    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...... 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...

  9. Intracellular Retention of Human Melanocortin-4 Receptor:A Molecular Mechanism Underlying Early-onset Obesity in F261S Pedigree of Chinese

    Institute of Scientific and Technical Information of China (English)

    QI-CHEN FANG; WEI-PING JIA; SHU-BING CAI; XIN-YU SHAO; RONG ZHANG; CONG-RONG WANG; YU-QIAN BAO; KUN-SAN XIANG

    2008-01-01

    To investigate how F261S mutation identified from Chinese obese patients affects the function of melanocortin 4 receptor (MC4R) and to analyze the obesity-related phenotypes in subjects carrying the F261S mutation. Methods F261S mutant of MC4R was generated by site-directed mutagenesis. Plasmids encoding wild-type or F261S mutant of MC4R were transfected into HEK293 and COS-7 cells to examine their functional characteristics. Signaling properties of F261S MC4R were assessed by measuring intracellular cAMP levels in response to α-MSH stimulation. Cell surface expression of F261S MC4R was compared with that of wild-type MC4R. Clinical examinations were performed in subjects carrying F261S mutation and in non-mutated controls. Results The α-MSH-stimulated reporter gene activity was significantly reduced in cells expressing F261S MC4R, with a maximal response equal to 57% of wild-type MC4R. The F261S mutation also led to a significant change in the EC value compared with the wild-type receptor (P<0.01). Immunofluorescent assay revealed a marked reduction in plasma membrane localization of the MC4R in cells expressing the F261S mutant receptor. The resting metabolic rate and fat composition of the mutant carriers were not significantly different from those of the non-mutated obese controls. Conclusions The decreased response to α-MSH due to the intracellular retention of MC4R may cause early-onset obesity in the F261S pedigree of Chinese.

  10. 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

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

    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...

  11. An obesity-associated risk allele within the FTO gene affects human brain activity for areas important for emotion, impulse control and reward in response to food images.

    Science.gov (United States)

    Wiemerslage, Lyle; Nilsson, Emil K; Solstrand Dahlberg, Linda; Ence-Eriksson, Fia; Castillo, Sandra; Larsen, Anna L; Bylund, Simon B A; Hogenkamp, Pleunie S; Olivo, Gaia; Bandstein, Marcus; Titova, Olga E; Larsson, Elna-Marie; Benedict, Christian; Brooks, Samantha J; Schiöth, Helgi B

    2016-05-01

    Understanding how genetics influences obesity, brain activity and eating behaviour will add important insight for developing strategies for weight-loss treatment, as obesity may stem from different causes and as individual feeding behaviour may depend on genetic differences. To this end, we examined how an obesity risk allele for the FTO gene affects brain activity in response to food images of different caloric content via functional magnetic resonance imaging (fMRI). Thirty participants homozygous for the rs9939609 single nucleotide polymorphism were shown images of low- or high-calorie food while brain activity was measured via fMRI. In a whole-brain analysis, we found that people with the FTO risk allele genotype (AA) had increased activity compared with the non-risk (TT) genotype in the posterior cingulate, cuneus, precuneus and putamen. Moreover, higher body mass index in the AA genotype was associated with reduced activity to food images in areas important for emotion (cingulate cortex), but also in areas important for impulse control (frontal gyri and lentiform nucleus). Lastly, we corroborate our findings with behavioural scales for the behavioural inhibition and activation systems. Our results suggest that the two genotypes are associated with differential neural processing of food images, which may influence weight status through diminished impulse control and reward processing.

  12. Variation at diabetes- and obesity-associated Loci may mirror neutral patterns of human population diversity and diabetes prevalence in India.

    Science.gov (United States)

    Raj, Srilakshmi M; Halebeedu, Pradeep; Kadandale, Jayarama S; Mirazon Lahr, Marta; Gallego Romero, Irene; Yadhav, Jamuna R; Iliescu, Mircea; Rai, Niraj; Crivellaro, Federica; Chaubey, Gyaneshwer; Villems, Richard; Thangaraj, Kumarasamy; Muniyappa, Kalappagowda; Chandra, H Sharat; Kivisild, Toomas

    2013-09-01

    South Asian populations harbor a high degree of genetic diversity, due in part to demographic history. Two studies on genome-wide variation in Indian populations have shown that most Indian populations show varying degrees of admixture between ancestral north Indian and ancestral south Indian components. As a result of this structure, genetic variation in India appears to follow a geographic cline. Similarly, Indian populations seem to show detectable differences in diabetes and obesity prevalence between different geographic regions of the country. We tested the hypothesis that genetic variation at diabetes- and obesity-associated loci may be potentially related to different genetic ancestries. We genotyped 2977 individuals from 61 populations across India for 18 SNPs in genes implicated in T2D and obesity. We examined patterns of variation in allele frequency across different geographical gradients and considered state of origin and language affiliation. Our results show that most of the 18 SNPs show no significant correlation with latitude, the geographic cline reported in previous studies, or by language family. Exceptions include KCNQ1 with latitude and THADA and JAK1 with language, which suggests that genetic variation at previously ascertained diabetes-associated loci may only partly mirror geographic patterns of genome-wide diversity in Indian populations.

  13. 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…

  14. 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

  15. Obesity and NAFLD: the role of bacteria and microbiota.

    Science.gov (United States)

    Duseja, Ajay; Chawla, Yogesh Kumar

    2014-02-01

    There are trillions of microorganisms in the human intestine collectively called gut microbiota. Obesity may be affected by the gut microbiota through energy harvesting and fat storage by the bacteria. Small intestinal bacterial overgrowth is also responsible for endotoxemia, systemic inflammation, and its consequences including obesity and nonalcoholic fatty liver disease (NAFLD). Relationship between gut microbiota and NAFLD is also dependent on altered choline and bile acid metabolism and endogenous alcohol production by gut bacteria. Further evidence linking gut microbiota with obesity and NAFLD comes from studies showing usefulness of probiotics in animals and patients with NAFLD. This article reviews the relationship among gut microbiota, obesity, and NAFLD.

  16. 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.

  17. 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 a...... argue that the relationship between obesity in people and in companion animals is closer and more complex than previously thought, and that obesity should be treated as a One Health problem.......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...

  18. Obesity in pregnancy.

    Science.gov (United States)

    Lim, Chu Chin; Mahmood, Tahir

    2015-04-01

    The prevalence of obesity has reached alarming proportions globally, and continues to rise in both developed and developing countries. Maternal obesity has become one of the most commonly occurring risk factors in obstetric practice. The 2003-2005 report of the Confidential Enquiries into Maternal Deaths in the United Kingdom highlighted obesity as a significant risk for maternal death [1]. More than half of all women who died from direct or indirect causes were either overweight or obese. For the mother, obesity increases the risk of obstetric complications during the antenatal, intrapartum and postnatal period, as well as contributing to technical difficulties with fetal assessment. The offspring of obese mothers also have a higher rate of perinatal morbidity and an increased risk of long-term health problems.

  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...... 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......., 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...

  20. Maternal obesity in Europe

    DEFF Research Database (Denmark)

    Devlieger, Roland; Benhalima, Katrien; Damm, Peter

    2016-01-01

    Paralleling the global epidemic of obesity figures in the general population, the incidence of maternal obesity (BMI>30kg/m(2) at the start of pregnancy) has been rising over the last world. While most European countries do not systematically report obesity figures in their pregnant population......, 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...... and offspring. These effects are often aggravated by the high incidence of abnormal glucose tolerance and excessive gestational weight gain found in this group. The main controversies around the management of the obese pregnant women are related to (1) the value of repeated weighing during pregnancy, (2...

  1. Predisposition to Obesity

    DEFF Research Database (Denmark)

    Olsen, Nanna Julie; Mortensen, Erik Lykke; Heitmann, Berit Lilienthal

    2012-01-01

    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...... 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...... status. Thus, we may be more successful in preventing obesity when targeting predisposed individuals, but more studies are needed before a firm conclusion can be drawn....

  2. 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...

  3. Anti-obesity effects of gut microbiota are associated with lactic acid bacteria.

    Science.gov (United States)

    Tsai, Yueh-Ting; Cheng, Po-Ching; Pan, Tzu-Ming

    2014-01-01

    The prevalence of obesity is rapidly becoming endemic in industrialized countries and continues to increase in developing countries worldwide. Obesity predisposes people to an increased risk of developing metabolic syndrome. Recent studies have described an association between obesity and certain gut microbiota, suggesting that gut microbiota might play a critical role in the development of obesity. Although probiotics have many beneficial health effects in humans and animals, attention has only recently been drawn to manipulating the gut microbiota, such as lactic acid bacteria (LAB), to influence the development of obesity. In this review, we first describe the causes of obesity, including the genetic and environmental factors. We then describe the relationship between the gut microbiota and obesity, and the mechanisms by which the gut microbiota influence energy metabolism and inflammation in obesity. Lastly, we focus on the potential role of LAB in mediating the effects of the gut microbiota in the development of obesity.

  4. The gut microbiota and obesity: from correlation to causality.

    Science.gov (United States)

    Zhao, Liping

    2013-09-01

    The gut microbiota has been linked with chronic diseases such as obesity in humans. However, the demonstration of causality between constituents of the microbiota and specific diseases remains an important challenge in the field. In this Opinion article, using Koch's postulates as a conceptual framework, I explore the chain of causation from alterations in the gut microbiota, particularly of the endotoxin-producing members, to the development of obesity in both rodents and humans. I then propose a strategy for identifying the causative agents of obesity in the human microbiota through a combination of microbiome-wide association studies, mechanistic analysis of host responses and the reproduction of diseases in gnotobiotic animals.

  5. Obesity: A multifactorial disease

    Directory of Open Access Journals (Sweden)

    Marianna Ntokou

    2010-04-01

    Full Text Available Obesity represents one of the most serious global health issues with approximately 310 million people presently affected. Main cause of it’s development is the increase of energy intake in regard to energy expenditure.Aim: The aim of the present study was to review the literature about the causes and treatment of obesity, as well as the anthropometrical measurements used for the assessment of obesity. The method οf this study included bibliography research from both the review and the research literature, mainly in the “pub med data base” which referred to the causes and treatment of obesity, as well as the anthropometrical measurements used for the assessment of obesity. Results: The prevalence of obesity has increased markedly, throughout the world. Although the etiology of obesity has not been fully understood yet, however it seems to be a multifactorial disease for which are responsible a great deal of psychological, environmental, genetic and behavioral factors. The most common anthropometrical measurement that is used for assessment of obesity is Body Mass Index (BMI and is calculated by the following equation: ΒΜΙ=Weight/Height2. A value of ΒΜΙ ≥ 30 kg/m2 equals obesity. Another simple test used to measure obesity is Waist to Hip Ratio, which measures abdominal adiposity. Values greater than 0,95 should be treated seriously as they normally indicate body fatness. The majority of studies show that life-style modification in conjunction with a well-balanced nutrition and regular physical exercise consist the cornerstone for the treatment and prevention of obesity.Conclusions: Obesity is a disease that can be preventable through modification of way of living. The development of proper strategy prevention capable to change attitudes, to promote nutrition and physical activity should be the primary goal of every community and government.

  6. Virtual screening against obesity.

    Science.gov (United States)

    Markt, P; Herdlinger, S; Schuster, D

    2011-01-01

    The development of novel drugs against obesity is one of the top priorities of worldwide drug research. In recent years, it has been facilitated by the application of virtual screening methods. In this review, we give a short introduction into obesity-related protein targets and computer-aided drug design techniques. Furthermore, we highlight the most successful virtual screening studies, outline their results, and provide suggestions for future anti-obesity drug development.

  7. Current mapping of obesity

    OpenAIRE

    Carmen Pérez Rodrigo

    2013-01-01

    Obesity is a major risk factor for non-communicable diseases (NCDs), such as diabetes, cardiovascular diseases, and cancers. The worldwide prevalence of obesity has almost doubled between 1980 and 2008. In some regions, such as Europe, the Eastern Mediterranean and the Americas, more than 50% of women are overweight. Tonga, Nauru and the Cook Islands show the highest prevalence of obesity worldwide, above 60% in men and in women. China and the United States are the countries that experienced ...

  8. Obesity and kidney protection

    OpenAIRE

    Chandra, Aravind; Biersmith, Michael; Tolouian, Ramin

    2014-01-01

    Context: Obesity, both directly and indirectly, increases the risk for a variety of disease conditions including diabetes, hypertension, liver disease, and certain cancers, which in turn, decreases the overall lifespan in both men and women. Though the cardiovascular risks of obesity are widely acknowledged, less often identified is the relationship between obesity and renal function. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO and Web of Sci...

  9. Medical management of obesity.

    Science.gov (United States)

    Klein, S

    2001-10-01

    Obesity has become a major health problem in many countries because of its high prevalence and causal relationship with serious medical complications. Many of the medical complications associated with obesity improve with intentional weight in a dose-dependent fashion, and even a modest weight loss of 50% of initial weight has beneficial effects. This article reviews the nonsurgical approaches for achieving weight loss in obese persons.

  10. Meta-Chlorophenylpiperazine enhances leptin sensitivity in diet-induced obese mice

    Science.gov (United States)

    Most forms of human obesity are characterized by impaired leptin sensitivity and, therefore, the effectiveness of anti-obesity leptin therapy in these leptin-resistant obese patients is marginal. Hence, the development of strategies to increase leptin sensitivity is of high priority in the field of ...

  11. 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.

  12. In Search of New Therapeutic Targets in Obesity Treatment: Sirtuins.

    Science.gov (United States)

    Kurylowicz, Alina

    2016-04-19

    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.

  13. Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects

    DEFF Research Database (Denmark)

    Arngrim, N; Simonsen, L; Holst, Jens Juul;

    2012-01-01

    The aim of this study was to investigate subcutaneous adipose tissue lymphatic drainage (ATLD) of macromolecules in lean and obese subjects and, furthermore, to evaluate whether ATLD may change in parallel with adipose tissue blood flow. Lean and obese male subjects were studied before and after...... an oral glucose load. Adipose-tissue blood flow was measured in the anterior subcutaneous abdominal adipose tissue by the (133)Xe-washout technique. ATLD was measured as the disappearance rate of (99m)Tc-labelled nanoaggregated human albumin, during fasting and after an oral glucose load. A significant...... the lymphatic system in obese subjects. Furthermore, they suggest that postprandial changes in ATLD taking place in lean subjects are not observed in obese subjects. This may have a role in the development of obesity-related inflammation in hypertrophic adipose tissue.International Journal of Obesity advance...

  14. Effects of Maternal Obesity on Fetal Programming: Molecular Approaches.

    Science.gov (United States)

    Neri, Caterina; Edlow, Andrea G

    2015-09-03

    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.

  15. Obesity in children with developmental and/or physical disabilities.

    Science.gov (United States)

    Bandini, Linda; Danielson, Melissa; Esposito, Layla E; Foley, John T; Fox, Michael H; Frey, Georgia C; Fleming, Richard K; Krahn, Gloria; Must, Aviva; Porretta, David L; Rodgers, Anne Brown; Stanish, Heidi; Urv, Tiina; Vogel, Lawrence C; Humphries, Kathleen

    2015-07-01

    Children with developmental or physical disabilities, many of whom face serious health-related conditions, also are affected by the current obesity crisis. Although evidence indicates that children with disabilities have a higher prevalence of obesity than do children without disabilities, little is known of the actual magnitude of the problem in this population. To address this concern, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) held a conference on obesity in children with intellectual, developmental, or physical disabilities, bringing together scientists and practitioners in the fields of obesity and disability to foster collaboration, identify barriers to healthy weight status in populations with disabilities, propose avenues to solutions through research and practice, and develop a research agenda to address the problem. This article describes current knowledge about prevalence of obesity in this population, discusses factors influencing obesity risk, and summarizes recommendations for research presented at the conference.

  16. Prevalence of asymptomatic urinary tract infections in morbidly obese dogs

    Science.gov (United States)

    Witzel, Angela L.; Bartges, Joseph W.; Moyers, Tamberlyn S.; Kirk, Claudia A.

    2016-01-01

    Background. Obesity has reached epidemic proportions in dogs and, as in humans, cost of care has increased due to associated comorbidities. In humans, asymptomatic urinary tract infections (UTI) may be more prevalent in the obese. Asymptomatic bacteriuria (AB) is the term used when UTI are asymptomatic. We hypothesized that morbidly obese dogs are similarly more likely to have asymptomatic bacteriuria than lean, overweight, and moderately obese dogs. Methods. A retrospective study was undertaken to explore a possible association between obesity and asymptomatic bacteriuria. Records from lean, overweight, and obese dogs receiving both a dual energy absorptiometry (DXA) scan and urine culture were included. Results. Six positive urine cultures were identified among 46 dogs fulfilling search criteria. All six positive cultures were found in dogs with body fat percentage of >45%. In dogs with body fat percentage of <45%, there were no positive urine cultures. Discussion. There was an increased prevalence of asymptomatic bacteriuria in the morbidly obese dogs in this study compared to those that were lean, overweight, or moderately obese. Whether antibiotic therapy is necessary in such cases is still being debated, but because asymptomatic bacteriuria may be associated with ascending infections, uroliths, or other complications, the data reported herein support the screening of obese patients for bacteriuria. PMID:26989606

  17. Prevalence of asymptomatic urinary tract infections in morbidly obese dogs.

    Science.gov (United States)

    Wynn, Susan G; Witzel, Angela L; Bartges, Joseph W; Moyers, Tamberlyn S; Kirk, Claudia A

    2016-01-01

    Background. Obesity has reached epidemic proportions in dogs and, as in humans, cost of care has increased due to associated comorbidities. In humans, asymptomatic urinary tract infections (UTI) may be more prevalent in the obese. Asymptomatic bacteriuria (AB) is the term used when UTI are asymptomatic. We hypothesized that morbidly obese dogs are similarly more likely to have asymptomatic bacteriuria than lean, overweight, and moderately obese dogs. Methods. A retrospective study was undertaken to explore a possible association between obesity and asymptomatic bacteriuria. Records from lean, overweight, and obese dogs receiving both a dual energy absorptiometry (DXA) scan and urine culture were included. Results. Six positive urine cultures were identified among 46 dogs fulfilling search criteria. All six positive cultures were found in dogs with body fat percentage of >45%. In dogs with body fat percentage of obese dogs in this study compared to those that were lean, overweight, or moderately obese. Whether antibiotic therapy is necessary in such cases is still being debated, but because asymptomatic bacteriuria may be associated with ascending infections, uroliths, or other complications, the data reported herein support the screening of obese patients for bacteriuria.

  18. Prevalence of asymptomatic urinary tract infections in morbidly obese dogs

    Directory of Open Access Journals (Sweden)

    Susan G. Wynn

    2016-03-01

    Full Text Available Background. Obesity has reached epidemic proportions in dogs and, as in humans, cost of care has increased due to associated comorbidities. In humans, asymptomatic urinary tract infections (UTI may be more prevalent in the obese. Asymptomatic bacteriuria (AB is the term used when UTI are asymptomatic. We hypothesized that morbidly obese dogs are similarly more likely to have asymptomatic bacteriuria than lean, overweight, and moderately obese dogs. Methods. A retrospective study was undertaken to explore a possible association between obesity and asymptomatic bacteriuria. Records from lean, overweight, and obese dogs receiving both a dual energy absorptiometry (DXA scan and urine culture were included. Results. Six positive urine cultures were identified among 46 dogs fulfilling search criteria. All six positive cultures were found in dogs with body fat percentage of >45%. In dogs with body fat percentage of <45%, there were no positive urine cultures. Discussion. There was an increased prevalence of asymptomatic bacteriuria in the morbidly obese dogs in this study compared to those that were lean, overweight, or moderately obese. Whether antibiotic therapy is necessary in such cases is still being debated, but because asymptomatic bacteriuria may be associated with ascending infections, uroliths, or other complications, the data reported herein support the screening of obese patients for bacteriuria.

  19. [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.

  20. DBS for Obesity

    Science.gov (United States)

    Franco, Ruth; Fonoff, Erich T.; Alvarenga, Pedro; Lopes, Antonio Carlos; Miguel, Euripides C.; Teixeira, Manoel J.; Damiani, Durval; Hamani, Clement

    2016-01-01

    Obesity is a chronic, progressive and prevalent disorder. Morbid obesity, in particular, is associated with numerous comorbidities and early mortality. In patients with morbid obesity, pharmacological and behavioral approaches often have limited results. Bariatric surgery is quite effective but is associated with operative failures and a non-negligible incidence of side effects. In the last decades, deep brain stimulation (DBS) has been investigated as a neurosurgical modality to treat various neuropsychiatric disorders. In this article we review the rationale for selecting different brain targets, surgical results and future perspectives for the use of DBS in medically refractory obesity. PMID:27438859

  1. DBS for Obesity

    Directory of Open Access Journals (Sweden)

    Ruth Franco

    2016-07-01

    Full Text Available Obesity is a chronic, progressive and prevalent disorder. Morbid obesity, in particular, is associated with numerous comorbidities and early mortality. In patients with morbid obesity, pharmacological and behavioral approaches often have limited results. Bariatric surgery is quite effective but is associated with operative failures and a non-negligible incidence of side effects. In the last decades, deep brain stimulation (DBS has been investigated as a neurosurgical modality to treat various neuropsychiatric disorders. In this article we review the rationale for selecting different brain targets, surgical results and future perspectives for the use of DBS in medically refractory obesity.

  2. Obesity and Exercise

    OpenAIRE

    2014-01-01

    Obesity is defined as the accumulation of abnormal or excessive fat in fat tissues that substantially disrupt health. The main reasons of obesity are excessive and unbalanced diet and lack of physical activity. Obesity and santral obesity leads to many diseases. Body mass index (weight (kg)/lenght (m2)) has been used extensively to define categories of body weight. All healthy adults aged 18-65 yr need moderate-intensity aerobic physical activity for a minimum of 30 min on five days each week...

  3. Economic Impact of Obesity.

    Science.gov (United States)

    Spieker, Elena A; Pyzocha, Natasha

    2016-03-01

    Parallel to rising obesity rates is an increase in costs associated with excess weight. Estimates of future direct (medical) and indirect (nonmedical) costs related to obesity suggest rising expenditures that will impose a significant economic burden to individuals and society as a whole. This article reviews research on direct and indirect medical costs and future economic trends associated with obesity and associated comorbidities. Cost disparities associated with subsets of the population experiencing higher than average rates of obesity are explored. Finally, potential solutions with the highest estimated impact are offered, and future directions are proposed.

  4. 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.

  5. Update on obesity surgery

    Institute of Scientific and Technical Information of China (English)

    Dan Eisenberg; Andrew J Duffy; Robert L Bell

    2006-01-01

    The prevalence of obesity in the United States has reached epidemic proportions. With more than 30 million Americans clinically obese, the younger population has also been affected. Surgical therapy should be offered to the severely obese patient who is refractory to nonsurgical therapy, as established by the 1991 NIH Consensus Conference on Gastrointestinal Surgery for Severe Obesity. Surgery is currently the most effective therapy for weight loss. It is far more effective than any other treatment modality, both in terms of the amount of weight loss and in terms of durability in maintaining weight loss.

  6. What Are Overweight and Obesity?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. Overweight and Obesity Español Also known as adiposity. Overweight and obesity ... more information. Rate This Content: NEXT >> Featured Video Obesity happens one pound at a time. So does ...

  7. Overweight, Obesity, and Weight Loss

    Science.gov (United States)

    ... Overweight, obesity, and weight loss fact sheet ePublications Overweight, obesity, and weight loss fact sheet Print this fact sheet Overweight, obesity, and weight loss fact sheet (full version) ( ...

  8. Treating Obesity As a Disease

    Science.gov (United States)

    ... Restaurant Deciphering the Menu Ordering Your Meal Eating Fast Food Dining Out Tips by Cuisine Physical Activity Fitness ... Childhood Obesity What is childhood obesity? Overweight in Children BMI in Children Is Childhood Obesity an Issue ...

  9. El factor de necrosis tumoral-α, la resistencia a la insulina, el metabolismo de lipoproteínas y la obesidad en humanos Tumor necrosis factor-α, insulin resistance, the lipoprotein metabolism and obesity in humans

    Directory of Open Access Journals (Sweden)

    M.ª M. Ramírez Alvarado

    2012-12-01

    produces proinflammatory molecules as tumor necrosis factor-α, which has local effects on adipocyte physiology and systemic effects in other organs. Many studies linking TNF-α, obesity, insulin resistance and lipid metabolism have been conducted in rats, rabbits and dogs, but the results observed in several of these studies have been conflicting and many of them have not been able to reproduce in humans, which on human makes difficult the interpretation of the effect of TNF-α on human metabolism. Objective: To conduct a systematic review of human studies which relates, TNF-α insulin resistance and lipoprotein metabolism. Methods: We searched the PubMed database for studies in humans, human tissue and human cell lines linking TNF-α, obesity, insulin resistance and lipoprotein. Results: There is a increased production of TNF-α on adipose tissue of obese. TNF-α decreases the cellular response to insulin in adipocytes, hepatocytes and human muscle cells. There is an increase of TNF-α in patients with dyslipidemia, and inactivation of TNF-α affects lipid metabolism. In human hepatocytes, TNF-α inhibits expression of APO AI, which may decrease the secretion of high density lipoproteins. TNF-α affects the excretion of cholesterol by inhibiting the enzyme cholesterol-7α-hydroxylase in hepatocytes. Conclusion: TNF-α decreases the cellular response to insulin, and has effects on the metabolism of cholesterol and lipoproteins in humans. A better understanding of the mechanisms of the inflammatory response induced obesity in humans, can lead to identifying new therapeutic targets that can prevent the complications associated with obesity.

  10. 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.

  11. Matrix metalloproteinases in exercise and obesity

    Directory of Open Access Journals (Sweden)

    Jaoude J

    2016-07-01

    Full Text Available Jonathan Jaoude,1 Yunsuk Koh2 1Department of Biology, 2Department of Health, Human Performance, and Recreation, Baylor University, Waco, TX, USA Abstract: Matrix metalloproteinases (MMPs are zinc- and calcium-dependent endoproteinases that have the ability to break down extracellular matrix. The large range of MMPs’ functions widens their spectrum of potential role as activators or inhibitors in tissue remodeling, cardiovascular diseases, and obesity. In particular, MMP-1, -2, and -9 may be associated with exercise and obesity. Thus, the current study reviewed the effects of different types of exercise (resistance and aerobic on MMP-1, -2, and -9. Previous studies report that the response of MMP-2 and -9 to resistance exercise is dependent upon the length of exercise training, since long-term resistance exercise training increased both MMP-2 and -9, whereas acute bout of resistance exercise decreased these MMPs. Aerobic exercise produces an inconsistent result on MMPs, although some studies showed a decrease in MMP-1. Obesity is related to a relatively lower level of MMP-9, indicating that an exercise-induced increase in MMP-9 may positively influence obesity. A comprehensive understanding of the relationship between exercise, obesity, and MMPs does not exist yet. Future studies examining the acute and chronic responses of these MMPs using different subject models may provide a better understanding of the molecular mechanisms that are associated with exercise, obesity, and cardiovascular disease. Keywords: cardiovascular disease, gelatinases, collagenases, TIMP

  12. 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

  13. Cardiac autonomic nervous system activity in obesity.

    Science.gov (United States)

    Liatis, Stavros; Tentolouris, Nikolaos; Katsilambros, Nikolaos

    2004-08-01

    The development of obesity is caused by a disturbance of energy balance, with energy intake exceeding energy expenditure. As the autonomic nervous system (ANS) has a role in the regulation of both these variables, it has become a major focus of investigation in the fields of obesity pathogenesis. The enhanced cardiac sympathetic drive shown in most of the studies in obese persons might be due to an increase in their levels of circulating insulin. The role of leptin needs further investigation with studies in humans. There is a blunted response of the cardiac sympathetic nervous system (SNS) activity in obese subjects after consumption of a carbohydrate-rich meal as well as after insulin administration. This might be due to insulin resistance. It is speculated that increased SNS activity in obesity may contribute to the development of hypertension in genetically susceptible individuals. It is also speculated that the increase in cardiac SNS activity under fasting conditions in obesity may be associated with high cardiovascular morbidity and mortality.

  14. Canine and feline obesity: a review of pathophysiology, epidemiology, and clinical management

    OpenAIRE

    Loftus JP; Wakshlag JJ

    2014-01-01

    John P Loftus, Joseph J Wakshlag Cornell University College of Veterinary Medicine, Veterinary Medical Center, Ithaca, NY, USAAbstract: Canine and feline obesity rates have reached pandemic proportions and are similar to those in humans, with approximately 30%–40% of dogs and cats being overweight to obese. Obesity has been associated with other health problems, including osteoarthritis, renal disease, skin disease, insulin resistance, and neoplasia in dogs, while in cats obesity is...

  15. Obesity and genomics: role of technology in unraveling the complex genetic architecture of obesity.

    Science.gov (United States)

    Apalasamy, Yamunah Devi; Mohamed, Zahurin

    2015-04-01

    Obesity is a complex and multifactorial disease that occurs as a result of the interaction between "obesogenic" environmental factors and genetic components. Although the genetic component of obesity is clear from the heritability studies, the genetic basis remains largely elusive. Successes have been achieved in identifying the causal genes for monogenic obesity using animal models and linkage studies, but these approaches are not fruitful for polygenic obesity. The developments of genome-wide association approach have brought breakthrough discovery of genetic variants for polygenic obesity where tens of new susceptibility loci were identified. However, the common SNPs only accounted for a proportion of heritability. The arrival of NGS technologies and completion of 1000 Genomes Project have brought other new methods to dissect the genetic architecture of obesity, for example, the use of exome genotyping arrays and deep sequencing of candidate loci identified from GWAS to study rare variants. In this review, we summarize and discuss the developments of these genetic approaches in human obesity.

  16. Surfactant protein D of the innate immune defence is inversely associated with human obesity and SP-D deficiency infers increased body weight in mice

    DEFF Research Database (Denmark)

    Sorensen, G.L.; Hjelmborg, J.V.B.; Leth-Larsen, R.

    2006-01-01

    Surfactant protein D (SP-D) is a key regulator of pathogen-induced inflammation. SP-D is further involved in lipid homeostasis in mouse lung and circulation and recent data have demonstrated that the body mass index (BMI; in kg/m(2)) is influenced by genes in common with SP-D. The objective of th.......0001) in males on normal chow. Fat percentage was significantly increased by 17% in the Spd-/- male mice (P = 0.003). We conclude, that there is an association between low levels or absent SP-D and obesity....

  17. 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.

  18. 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......, and 8 h in the absence (control trial) and presence of experimental hyperglycemia (hyperglycemia trial; 5.4 mM above basal). Circulating levels of glucose, insulin, ghrelin, and peptide YY (PYY)3-36 and visual analog scale ratings of satiety were measured throughout each trial. In the control trial...

  19. 用ENDEAVOUR软件鉴定肥胖症致病基因GAD2%Verification of candidate gene GAD2 for human obesity by ENDEAVOUR

    Institute of Scientific and Technical Information of China (English)

    张焕萍; 张小白

    2011-01-01

    Disease genes identification is very important for understanding disease pathogenesis and improving clinic treatment. The computational gene prioritization tools have the advantages of huge data sources, efficient data processing and low costs. Many researchers have studied the disputing candidate disease gene GAD2 for obesity on chromosome 1 Op 12 by association studies but obtained contradictory conclusions. In this paper, the probability of gene GAD2 being an obesity disease gene is verified by the computational gene prioritization tool ENDEAVOUR. The prioritization strategies of ENDEAVOUR are based on the similarity between the candidate gene and the profile derived from genes already known to be involved in the processes (the training genes) by genomic data fusion. In the computational results, the first rank of gene GAD2 means that the probability of gene GAD2 being an obesity disease gene is high. The results are helpful to explain the biological mechanism of gene GAD2 and genetic factors of the complex obesity disease..%鉴别复杂疾病致病基因对于治疗和预防疾病作用非常重要,致病基因预测软件是鉴别致病基因的有效工具.位于染色体10p12的基因GAD2是尚有争议的肥胖基因,许多研究者用实验方法研究基因GAD2,却得出了不一致的结论.基于生物计算的致病基因预测软件能弥补实验的不足,已成为揭示疾病发病机理和预测致病基因的有效途径,本文采用ENDEAVOUR软件来验证基因GAD2是否为肥胖症致病基因,该软件运用多种生物数据,根据每一个候选基因与已知致病基因的相似程度以排序,结果在35个候选基因中,基因GAD2排在最前面,表明基因GAD2最可能是肥胖症致病基因.预测结果有利于重新解释基因GAD2的生物功能,促使肥胖症药物的研制及治疗水平的提高.

  20. Obesidad monogénica humana: papel del sistema leptina-melanocortina en la regulación de la ingesta de alimentos y el peso corporal en humanos Monogenic human obesity: role of the leptin-melanocortin system in the regulation of food intake and body weight in humans

    Directory of Open Access Journals (Sweden)

    E. González Jiménez

    2012-08-01

    Full Text Available La obesidad humana es un trastorno de origen multifactorial en el que intervienen factores tanto genéticos como ambientales. La existencia de alteraciones genéticas que dan origen a obesidades monogénicas resulta muy interesante para el estudio de los mecanismos que contribuyen a un aumento de la ingesta de energía y la acumulación de grasa en el cuerpo. La mayoría de los genes implicados en obesidad monogénica se relacionan con el sistema de la leptina-melanocortinas, de ahí la importancia de su estudio a través de mutaciones naturales en ratones. Así, se han descrito mutaciones relacionadas con obesidad humana de tipo monogénica en la leptina y su receptor, proopiomelanocortina y prohormona convertasa 1. El objetivo de este trabajo ha sido ofrecer una revisión actualizada acerca de las principales características y funcionamiento del sistema leptina-melanocortinas, así como de sus implicaciones y potencialidades en el proceso de regulación de la ingesta alimentaria y control del peso corporal.Human obesity is a disorder of multifactorial origin in which genetic and environmental factors are involved. To understand the mechanisms regulating energy intake and fat accumulation in the body, it is important to study the genetic alterations causing monogenic obesity. Most of the genes involved in monogenic obesity are associated with the leptin-melanocortin system; hence the importance of studying this system by analysing natural mutations in mice. Previous studies have described mutations in leptin and its receptor, proopiomelanocortin and prohormone convertase 1 associated with human obesity of monogenic origin. The aim of this study is to provide an updated review of the main characteristics and functioning of the leptin-melanocortin system, and its implications and potentialities in regulating food intake and body weight.

  1. 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.

  2. 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.

  3. 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

  4. Obesity and pregnancy

    DEFF Research Database (Denmark)

    Andreasen, Kirsten Riis; Andersen, Malene Lundgren; Schantz, Anne Louise

    2004-01-01

    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....

  5. Childhood Overweight and Obesity

    Science.gov (United States)

    ... Home Prevention and Wellness Food and Nutrition Healthy Food Choices Childhood Overweight and Obesity Childhood Overweight and Obesity Family HealthFood and NutritionHealthy Food ChoicesKids and TeensPrevention and WellnessWeight Loss and Diet ...

  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. Battling the Obesity Epidemic.

    Science.gov (United States)

    Kelly, Mark; Moag-Stahlberg, Alicia

    2002-01-01

    Describes causes of overweight and obesity in children; cites research linking good nutrition and a child's capacity to learn; includes six Web-based links to resources to help principals and teachers reduce the serious problem of overweight and obese children. (PKP)

  8. Obesity and craniopharyngioma

    Directory of Open Access Journals (Sweden)

    Bruzzi Patrizia

    2011-08-01

    Full Text Available Abstract An epidemic of pediatric obesity has occurred across the world in recent years. There are subgroups within the population at high-risk of becoming obese and especially of having experience of precocious cardiovascular and metabolic co-morbidities of obesity. One of these subgroups comprises patients treated for childhood cancers and namely survivors of craniopharyngioma. The high incidence of obesity in this group makes these patients an important disease model to better understand the metabolic disturbances and the mechanisms of weight gain among cancer survivors. The hypothalamic-pituitary axis damage secondary to cancer therapies or to primary tumor location affect long-term outcomes. Nevertheless, the aetiology of obesity in craniopharyngioma is not yet fully understood. The present review has the aim of summarizing the published data and examining the most accepted mechanisms and main predisposing factors related to weight gain in this particular population.

  9. Obesity and cancer.

    Science.gov (United States)

    Brawer, Rickie; Brisbon, Nancy; Plumb, James

    2009-09-01

    Obesity has become the second leading preventable cause of disease and death in the United States, trailing only tobacco use. Weight control, dietary choices, and levels of physical activity are important modifiable determinants of cancer risk. Physicians have a key role in integrating multifactorial approaches to prevention and management into clinical care and advocating for systemic prevention efforts. This article provides an introduction to the epidemiology and magnitude of childhood and adult obesity; the relationship between obesity and cancer and other chronic diseases; potential mechanisms postulated to explain these relationships; a review of recommended obesity treatment and assessment guidelines for adults, adolescents, and children; multilevel prevention strategies; and an approach to obesity management in adults using the Chronic Care Model.

  10. 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....

  11. 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...

  12. Sexual function and obesity

    DEFF Research Database (Denmark)

    Larsen, S H; Wagner, G; Heitmann, B L

    2007-01-01

    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...... 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...... activity among both men and women after weight loss intervention. CONCLUSION: Support for the assumption that obesity is associated with ED was found in both prospective and cross-sectional studies. FSD was not adequately described in the literature and prospective studies are needed here. Results from...

  13. 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

  14. Refeeding hypertension in dietary obesity

    Energy Technology Data Exchange (ETDEWEB)

    Ernsberger, P.; Nelson, D.O. (Northwestern Univ. Medical School, Chicago, IL (USA))

    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 {beta}-adrenergic receptors were downregulated, as indicated by a 40% decrease in the maximum binding of ({sup 3}H)dihydroalpranolol; and (2) the decrease in heart rate as a result of {beta}-blockade was enhanced. Refeeding hypertension in the dietary obese rat may be a potential animal model for some forms of human obesity-related hypertension.

  15. Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft-versus-host-like disease and the role of host major histocompatibility complex

    Science.gov (United States)

    King, M A; Covassin, L; Brehm, M A; Racki, W; Pearson, T; Leif, J; Laning, J; Fodor, W; Foreman, O; Burzenski, L; Chase, T H; Gott, B; Rossini, A A; Bortell, R; Shultz, L D; Greiner, D L

    2009-01-01

    Immunodeficient non-obese diabetic (NOD)-severe combined immune-deficient (scid) mice bearing a targeted mutation in the gene encoding the interleukin (IL)-2 receptor gamma chain gene (IL2rγnull) engraft readily with human peripheral blood mononuclear cells (PBMC). Here, we report a robust model of xenogeneic graft-versus-host-like disease (GVHD) based on intravenous injection of human PBMC into 2 Gy conditioned NOD-scid IL2rγnull mice. These mice develop xenogeneic GVHD consistently (100%) following injection of as few as 5 × 106 PBMC, regardless of the PBMC donor used. As in human disease, the development of xenogeneic GVHD is highly dependent on expression of host major histocompatibility complex class I and class II molecules and is associated with severely depressed haematopoiesis. Interrupting the tumour necrosis factor-α signalling cascade with etanercept, a therapeutic drug in clinical trials for the treatment of human GVHD, delays the onset and progression of disease. This model now provides the opportunity to investigate in vivo mechanisms of xenogeneic GVHD as well as to assess the efficacy of therapeutic agents rapidly. PMID:19659776

  16. Long-term human immune system reconstitution in non-obese diabetic (NOD)-Rag (-)-γ chain (-) (NRG) mice is similar but not identical to the original stem cell donor.

    Science.gov (United States)

    Harris, D T; Badowski, M; Balamurugan, A; Yang, O O

    2013-12-01

    The murine immune system is not necessarily identical to it human counterpart, which has led to the construction of humanized mice. The current study analysed whether or not a human immune system contained within the non-obese diabetic (NOD)-Rag1(null) -γ chain(null) (NRG) mouse model was an accurate representation of the original stem cell donor and if multiple mice constructed from the same donor were similar to one another. To that end, lightly irradiated NRG mice were injected intrahepatically on day 1 of life with purified cord blood-derived CD34(+) stem and progenitor cells. Multiple mice were constructed from each cord blood donor. Mice were analysed quarterly for changes in the immune system, and followed for periods up to 12 months post-transplant. Mice from the same donor were compared directly with each other as well as with the original donor. Analyses were performed for immune reconstitution, including flow cytometry, T cell receptor (TCR) and B cell receptor (BCR) spectratyping. It was observed that NRG mice could be 'humanized' long-term using cord blood stem cells, and that animals constructed from the same cord blood donor were nearly identical to one another, but quite different from the original stem cell donor immune system.

  17. Morphometric Analysis of Recognized Genes for Autism Spectrum Disorders and Obesity in Relationship to the Distribution of Protein-Coding Genes on Human Chromosomes

    Directory of Open Access Journals (Sweden)

    Austen B. McGuire

    2016-05-01

    Full Text Available Mammalian chromosomes are comprised of complex chromatin architecture with the specific assembly and configuration of each chromosome influencing gene expression and function in yet undefined ways by varying degrees of heterochromatinization that result in Giemsa (G negative euchromatic (light bands and G-positive heterochromatic (dark bands. We carried out morphometric measurements of high-resolution chromosome ideograms for the first time to characterize the total euchromatic and heterochromatic chromosome band length, distribution and localization of 20,145 known protein-coding genes, 790 recognized autism spectrum disorder (ASD genes and 365 obesity genes. The individual lengths of G-negative euchromatin and G-positive heterochromatin chromosome bands were measured in millimeters and recorded from scaled and stacked digital images of 850-band high-resolution ideograms supplied by the International Society of Chromosome Nomenclature (ISCN 2013. Our overall measurements followed established banding patterns based on chromosome size. G-negative euchromatic band regions contained 60% of protein-coding genes while the remaining 40% were distributed across the four heterochromatic dark band sub-types. ASD genes were disproportionately overrepresented in the darker heterochromatic sub-bands, while the obesity gene distribution pattern did not significantly differ from protein-coding genes. Our study supports recent trends implicating genes located in heterochromatin regions playing a role in biological processes including neurodevelopment and function, specifically genes associated with ASD.

  18. Leptin Enhances the Potency of Circulating Angiogenic Cells via Src Kinase and Integrin αvβ5: Implications for Angiogenesis in Human Obesity

    Science.gov (United States)

    Heida, Nana-Maria; Leifheit-Nestler, Maren; Schroeter, Marco R.; Müller, Jan-Peter; Cheng, I-Fen; Henkel, Sarah; Limbourg, Anne; Limbourg, Florian P.; Alves, Frauke; Quigley, James P.; Ruggeri, Zaverio M.; Hasenfuss, Gerd; Konstantinides, Stavros; Schäfer, Katrin

    2010-01-01

    Objective The present study investigated the capacity of the adipokine leptin to promote angiogenesis by modulating the function of circulating angiogenic cells (CAC). Methods and Results In vitro, leptin specifically promoted CAC adhesion to tubular endothelial structures and migration along outgrowing sprouts of endothelial cells. In vivo, stimulation of CAC with leptin increased their capacity to promote new vessel formation in the chorioallantoic membrane of chicken embryos and to improve neovascularization of ischemic murine hindlimbs. These effects required the phosphorylation of αvβ5 integrins which depended on the interaction of leptin with its receptor ObR, and on JAK2- and PLCγ-mediated activation of Src kinase. Protein tyrosine phosphatase (PTP1)B, a negative regulator of leptin signaling, was overexpressed in CAC from obese, hyperleptinemic individuals, and this was associated with insensitivity of CAC to the angiogenic effects of leptin. Weight loss (by 30±15 kg) normalized PTP1B expression in CAC and restored their responsiveness to leptin. A similar, dose-dependent response was found after incubation of CAC from the obese with a PTP1B inhibitor ex vivo. Conclusions Our results point to the ObR-Src kinase-αvβ5 cross-talk as a distinct novel component of the network of specific interactions between integrins and cytokine receptors in angiogenesis. PMID:19910644

  19. Morphometric Analysis of Recognized Genes for Autism Spectrum Disorders and Obesity in Relationship to the Distribution of Protein-Coding Genes on Human Chromosomes.

    Science.gov (United States)

    McGuire, Austen B; Rafi, Syed K; Manzardo, Ann M; Butler, Merlin G

    2016-05-05

    Mammalian chromosomes are comprised of complex chromatin architecture with the specific assembly and configuration of each chromosome influencing gene expression and function in yet undefined ways by varying degrees of heterochromatinization that result in Giemsa (G) negative euchromatic (light) bands and G-positive heterochromatic (dark) bands. We carried out morphometric measurements of high-resolution chromosome ideograms for the first time to characterize the total euchromatic and heterochromatic chromosome band length, distribution and localization of 20,145 known protein-coding genes, 790 recognized autism spectrum disorder (ASD) genes and 365 obesity genes. The individual lengths of G-negative euchromatin and G-positive heterochromatin chromosome bands were measured in millimeters and recorded from scaled and stacked digital images of 850-band high-resolution ideograms supplied by the International Society of Chromosome Nomenclature (ISCN) 2013. Our overall measurements followed established banding patterns based on chromosome size. G-negative euchromatic band regions contained 60% of protein-coding genes while the remaining 40% were distributed across the four heterochromatic dark band sub-types. ASD genes were disproportionately overrepresented in the darker heterochromatic sub-bands, while the obesity gene distribution pattern did not significantly differ from protein-coding genes. Our study supports recent trends implicating genes located in heterochromatin regions playing a role in biological processes including neurodevelopment and function, specifically genes associated with ASD.

  20. Current mapping of obesity

    Directory of Open Access Journals (Sweden)

    Carmen Pérez Rodrigo

    2013-09-01

    Full Text Available Obesity is a major risk factor for non-communicable diseases (NCDs, such as diabetes, cardiovascular diseases, and cancers. The worldwide prevalence of obesity has almost doubled between 1980 and 2008. In some regions, such as Europe, the Eastern Mediterranean and the Americas, more than 50% of women are overweight. Tonga, Nauru and the Cook Islands show the highest prevalence of obesity worldwide, above 60% in men and in women. China and the United States are the countries that experienced the largest absolute increase in the number of overweight and obese people between 1980 and 2008, followed by Brazil and Mexico. The regions with the largest increase in the prevalence of female obesity were Central Latin America, Oceania and Southern Latin America. Updated data provide evidence that the progression of the epidemic has effectively slowed for the past ten years in several countries. In low-income countries obesity is generally more prevalent among the better-off, while disadvantaged groups are increasingly affected as countries grow. Many studies have shown an overall socio-economic gradient in obesity in modern industrialized societies. Rates tend to decrease progressively with increasing socio-economic status. Children obesity rates in Spain are amongst the highest in the OECD. One in 3 children aged 13 to 14 are overweight. Overweight in infants and young children is observed in the upper middle-income countries. However, the fastest growth occurs in the group of lower middle-income countries. There is a growing body of evidence for an inverse association between SES and child obesity in developed countries. The prevalence of overweight and obesity is high in all age groups in many countries, but especially worrying in children and adolescents in developed countries and economies in transition.

  1. Current mapping of obesity.

    Science.gov (United States)

    Pérez Rodrigo, Carmen

    2013-09-01

    Obesity is a major risk factor for non-communicable diseases (NCDs), such as diabetes, cardiovascular diseases, and cancers. The worldwide prevalence of obesity has almost doubled between 1980 and 2008. In some regions, such as Europe, the Eastern Mediterranean and the Americas, more than 50% of women are overweight. Tonga, Nauru and the Cook Islands show the highest prevalence of obesity worldwide, above 60% in men and in women. China and the United States are the countries that experienced the largest absolute increase in the number of overweight and obese people between 1980 and 2008, followed by Brazil and Mexico. The regions with the largest increase in the prevalence of female obesity were Central Latin America, Oceania and Southern Latin America. Updated data provide evidence that the progression of the epidemic has effectively slowed for the past ten years in several countries. In low-income countries obesity is generally more prevalent among the better-off, while disadvantaged groups are increasingly affected as countries grow. Many studies have shown an overall socio-economic gradient in obesity in modern industrialized societies. Rates tend to decrease progressively with increasing socio-economic status. Children obesity rates in Spain are amongst the highest in the OECD. One in 3 children aged 13 to 14 are overweight. Overweight in infants and young children is observed in the upper middle-income countries. However, the fastest growth occurs in the group of lower middle-income countries. There is a growing body of evidence for an inverse association between SES and child obesity in developed countries. The prevalence of overweight and obesity is high in all age groups in many countries, but especially worrying in children and adolescents in developed countries and economies in transition.

  2. 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 ...... 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......RNAs are differentially expressed in subcutaneous adipose tissue between the lean and obese group of pigs, and in addition gender specific significant differential expression is observed for a number of miRNAs. The differentially expressed miRNAs have been verified using qPCR. The results of these studies in general...

  3. 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.

  4. Establishment and evaluation of human flora associated animals related with Kazakh obese children in Xinjiang%新疆哈萨克族肥胖儿童菌群人源化动物模型的建立及评价

    Institute of Scientific and Technical Information of China (English)

    刘新彩; 李敏; 徐佩茹

    2016-01-01

    Objective To establish human flora associated (HFA) animal models related with Kazakh obese children in Xinjiang based on germ-free (GF) mice, study the engraftment of intestinal flora in GF mice, to provide a new way for the further study of the physiopathologic mechanism of Kazakh obese children. Methods We collected fresh feces from Kazakh obese children, and 20 GF C57BL/6J mice (half male and half female) were selected. The GF mice received gavage inoculation of bacterium suspension from Kazakh obese children when they were three-week-old. On the one month after inoculation, fresh feces samples were collected, PCR-DGGE method was adopted to detect, similarity UPGMA clustering analysis method was used to analyze the DGGE profiles, in order to understand the engraftment of intestinal flora in HFA animal models. Results The average richness of flora in HFA mice was 0.76 times of Kazakh obesity children; the average Evenness and Shannon-Wiener of flora in HFA mice were below Kazakh obesity children; but there was no obvious statistical significance; the similarity dice of Kazakh obesity children and HFA mice was 64%, the similarity between HFA mice was 73%-94%; Most gut microbiota of female mice differed from those of male mice in the cluster profile. Conclusion (1) It was successful to simulate the character intestinal flora environment of Kazakh obese children based on GF C57BL/6J mice. (2) HFA animal model is a new method for study of the relationship between Kazakh obese children and intestinal flora.%目的:利用无菌小鼠建立新疆哈萨克族肥胖儿童菌群人源化(HFA)动物模型,研究哈萨克族肥胖儿童的肠道菌群在无菌小鼠体内的定植规律,为深入研究哈萨克族儿童肥胖的病理生理机制提供了一种新的选择方式。方法收集新疆哈萨克族肥胖儿童新鲜粪便样本,选取20只无菌级 C57BL/6J 小鼠(雌雄各半),于无菌小鼠3周龄时,开始灌胃接种哈萨克族肥胖

  5. Contemporary pharmacological obesity treatments

    Directory of Open Access Journals (Sweden)

    Kaszubska Katarzyna

    2016-06-01

    Full Text Available In the last few years, obesity has become a global epidemic. Consequently, worldwide costs associated with managing obesity and obesity-related comorbidities are huge. Numerous studies have focused on discerning the appropriate proper treatment of weight related problems such as overweight and obesity. Moreover, many clinical trials have been conducted for many years in order to introduce effective anti-obesity drugs. The aim of the present review is to provide an overview of current and future pharmacotherapy for obesity, and to provide the reader with a determination of the concentration and composition of long and short term anti-obesity drugs, doing so by placing emphasis on pharmacotherapy and up-to-day solutions. It should be noted that, currently, the worldwide pharmacotherapy is represented by phendimetrazine, benzphetamine and diethylpropion, as well as by orlistat, lorcaserin, phentermine/topiramate, naltrexone/bupropion and liraglutide. In our paper, individual cases of patients’ needs are thoroughly illustrated by way of examples. Medical prescriptions and contraindications are also described.

  6. 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

  7. 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.

  8. The chronobiology, etiology and pathophysiology of obesity

    OpenAIRE

    M. Garaulet; Ordovás, JM; Madrid, JA

    2010-01-01

    The effect of CD on human health is an emerging issue. Many records link CD with diseases such as cancer, cardiovascular, cognitive impairment and obesity, all of them conducive to premature aging. The amount of sleep has declined by 1.5 h over the past century, accompanied by an important increase in obesity. Shift work, sleep deprivation and exposure to bright light at night increase the prevalence of adiposity. Animal models have shown that mice with Clock gene disruption are prone to deve...

  9. Role of Dietary Soy Protein in Obesity

    Directory of Open Access Journals (Sweden)

    Manuel T. Velasquez, Sam J. Bhathena

    2007-01-01

    Full Text Available Soy protein is an important component of soybeans and provides an abundant source of dietary protein. Among the dietary proteins, soy protein is considered a complete protein in that it contains ample amounts of all the essential amino acids plus several other macronutrients with a nutritional value roughly equivalent to that of animal protein of high biological value. Soy protein is unique among the plant-based proteins because it is associated with isoflavones, a group of compounds with a variety of biological properties that may potentially benefit human health. An increasing body of literature suggests that soy protein and its isoflavones may have a beneficial role in obesity. Several nutritional intervention studies in animals and humans indicate that consumption of soy protein reduces body weight and fat mass in addition to lowering plasma cholesterol and triglycerides. In animal models of obesity, soy protein ingestion limits or reduces body fat accumulation and improves insulin resistance, the hallmark of human obesity. In obese humans, dietary soy protein also reduces body weight and body fat mass in addition to reducing plasma lipids. Several potential mechanisms whereby soy protein may improve insulin resistance and lower body fat and blood lipids are discussed and include a wide spectrum of biochemical and molecular activities that favorably affect fatty acid metabolism and cholesterol homeostasis. The biologic actions of certain constituents of soy protein, particularly conglycinin, soyasaponins, phospholipids, and isoflavones, that relate to obesity are also discussed. In addition, the potential of soy protein in causing food allergy in humans is briefly discussed.

  10. [Obesity and cardiovascular disease].

    Science.gov (United States)

    Poirier, Paul; Després, Jean-Pierre

    2003-10-01

    Available evidence clearly indicates a rapid progression in the prevalence of obesity worldwide. As a consequence, there has also been a marked increase in the prevalence of type 2 diabetes all over the world and this chronic metabolic disease is now considered as a coronary heart disease risk equivalent. However, even in the absence of the hyperglycaemic state which characterizes type 2 diabetic patients, non diabetic individuals with a specific form of obesity, named abdominal obesity, often show clustering metabolic abnormalities which include high triglyceride levels, increased apolipoprotein B, small dense low density lipoproteins and decreased high density lipoproteins-cholesterol levels, a hyperinsulinemic-insulin resistant state, alterations in coagulation factors as well as an inflammatory profile. This agglomeration of abnormalities has been referred to as the metabolic syndrome which can be identified by the presence of three of the five following variables: abdominal obesity, elevated triglyceride concentrations, low HDL-cholesterol levels, increased blood pressure and elevated fasting glucose. Post-mortem analyses of coronary arteries have indicated that obesity (associated with a high accumulation of abdominal fat measured at autopsy) was predictive of earlier and greater extent of large vessels atherosclerosis as well as increase of coronary fatty streaks. Metabolic syndrome linked to abdominal obesity is also predictive of recurrent coronary events both in post-myocardial infarction patients and among coronary artery disease men who underwent a revascularization procedures. It is suggested that until the epidemic progression of obesity is stopped and obesity prevented or at least properly managed, cardiologists will be confronted to an evolving contribution of risk factors where smoking, hypercholesterolemia and hypertension may be relatively less prevalent but at the expense of a much greater contribution of abdominal obesity and related features

  11. [Obesity Paradox and Stroke].

    Science.gov (United States)

    Baumgartner, Ralf; Oesch, Lisa; Sarikaya, Hakan

    2016-07-06

    The obesity paradox suggests that overweight and obese patients of older age may have higher survival rates after stroke as compared to normalweight patients. However, the results need a cautious interpretation due to selection bias, treatment bias and different patients’ characteristics. Moreover, randomized studies that prove a benefit of weight reduction are still lacking. As obesity is an independet risk factor for stroke, weight reduction should still be recommended in overweight patients. Randomized-controlled studies are needed to prove the effect of weight reduction on morbidity and mortality after stroke.

  12. The childhood obesity epidemic: A mini review

    Directory of Open Access Journals (Sweden)

    Lubna Mahmood

    2015-01-01

    Full Text Available Obesity is a medical condition resulting from the accumulation of excess fat in the human body to the extent that it might have great harm effects on the human health by increasing the diseases lowering the average life expectancy. A person who has a body mass index (BMI of more than 30 kg/m 2 is classified as obese; this is how obesity can be defined for adult, which is different than that in children. To account for variability by sex and age, BMI in children must be compared with sex- and age-specific reference values (Centers for Disease Control growth chart. The terminology that is used for high BMI-for-age in children in has been based on the recommendation of an expert committee convened by federal agencies. Parents can be a good example for their children by modeling healthful eating behaviors and being physically active. Parents can also be effective advocates by being involved in efforts in their schools, and community to expand the access and availability of opportunities for physical activity and healthful eating. In the case of being an obese child, that means suffering from many health problems and obesity-related diseases such as elevated blood pressure, high cholesterol, diabetes and heart diseases. Diabetes is considered as one of the obesity-related diseases; type 2 diabetes in children has linked with obesity; when the pancreas starts to produce the insulin hormone, excess body fat will not allow child's body to use the insulin as it should be which can lead to being a diabetic patient. Schools also play a vital role in teaching the students on how to eat properly and select the best meal with keeping their bodies flexible by doing physical activities. It is important in order to keep children away from being in disasters by having a lot of obesity-related diseases (e.g., heart attacks and diabetes, which can lead to premature death in obese children. Children must be healthy since those children growing up in today's world

  13. Obesity and exercise in adoloscent period

    Directory of Open Access Journals (Sweden)

    Eda Mendeş

    2011-10-01

    Full Text Available Adolescence period is a special period during which fastest growth and development occur in humans and which includes transition from childhood to adulthood. World Health Organization (WHO define 10-19 age-group individuals as adolescence and 15- 24 age-group individuals as youthood. That today’s community lacks knowledge of workout, inadequate awareness of the benefits of workout to human health and acceptance of the continuity of sedentary life gives rise to the incidence of lots of chronic diseases such as high-blood pressure, cardio-pulmonary diseases, obesity and diabetes.In recent years, childhood and adolescence obesity has become an important health problem as a result of the decline in physical activities. In this context, workout along with balanced diet is one of the precautions that can be suggested in terms of the prevention of obesity. The purpose of this study (compilation is to provide information on keeping human health by means of an awareness of workout in adolescence period which is the most important stage preceding adulthood; to summarize the issue in relation to the written documents existing in the relevant literature, and to make suggestions about healthy future generations through workout in adolescence period.In conclusion, successful results regarding the treatment of obesity in adolescence can be achieved through aerobics along with low-calorie diet.

  14. Obesity and exercise in adoloscent period

    Directory of Open Access Journals (Sweden)

    Eda Mendes

    2011-10-01

    Full Text Available             Adolescence period is a special period during which fastest growth and development occur in humans and which includes transition from childhood to adulthood. World Health Organization (WHO define 10-19 age-group individuals as adolescence and 15- 24 age-group individuals as youthood.             That today’s community lacks knowledge of workout, inadequate awareness of the benefits of workout to human health and acceptance of the continuity of sedentary life gives rise to the incidence of lots of  chronic diseases such as  high-blood pressure, cardio-pulmonary diseases, obesity and diabetes. In recent years, childhood and adolescence obesity has become an important health problem as a result of the decline in physical activities. In this context, workout along with balanced diet is one of the precautions that can be suggested in terms of the prevention of obesity. The purpose of this study (compilation is to provide information on keeping human health by means of an awareness of workout in adolescence period which is the most important stage preceding adulthood; to summarize the issue in relation to the written documents existing in the relevant literature, and  to make suggestions  about healthy future generations through workout in adolescence period. In conclusion, successful results regarding the treatment of obesity in adolescence can be achieved through aerobics along with low-calorie diet.

  15. Desaturation of excess intramyocellular triacylglycerol in obesity

    DEFF Research Database (Denmark)

    Haugaard, S B; Madsbad, S; Mu, Huiling;

    2010-01-01

    diabetes (T2DM), body mass index (BMI)=35.5+/-0.8 kg m(-2)) and 25 men, age 49+/-2 years (20 obese including 6 T2DM, BMI=35.8+/-0.8 kg m(-2))), IMTG FA composition was determined by gas-liquid chromatography after separation from phospholipids by thin-layer chromatography. RESULTS: Independently of gender......OBJECTIVE: Excess intramyocellular triacylglycerol (IMTG), found especially in obese women, is slowly metabolized and, therefore, prone to longer exposure to intracellular desaturases. Accordingly, it was hypothesized that IMTG content correlates inversely with IMTG fatty acid (FA) saturation...... in sedentary subjects. In addition, it was validated if IMTG palmitic acid is associated with insulin resistance as suggested earlier. DESIGN: Cross-sectional human study. SUBJECTS: In skeletal muscle biopsies, which were obtained from sedentary subjects (34 women, age 48+/-2 years (27 obese including 7 type 2...

  16. 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.

  17. 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.

  18. Monomeric tartrate resistant acid phosphatase induces insulin sensitive obesity.

    Directory of Open Access Journals (Sweden)

    Pernilla Lång

    Full Text Available BACKGROUND: 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. PRINCIPAL FINDINGS: 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. CONCLUSION: Monomeric TRAP, most likely secreted from adipose tissue macrophages, induces hyperplastic obesity with normal adipocyte lipid metabolism and insulin sensitivity.

  19. Mesolimbic dopamine and its neuromodulators in obesity and binge eating.

    Science.gov (United States)

    Naef, Lindsay; Pitman, Kimberley A; Borgland, Stephanie L

    2015-12-01

    Obesity has reached epidemic prevalence, and much research has focused on homeostatic and nonhomeostatic mechanisms underlying overconsumption of food. Mesocorticolimbic circuitry, including dopamine neurons of the ventral tegmental area (VTA), is a key substrate for nonhomeostatic feeding. The goal of the present review is to compare changes in mesolimbic dopamine function in human obesity with diet-induced obesity in rodents. Additionally, we will review the literature to determine if dopamine signaling is altered with binge eating disorder in humans or binge eating modeled in rodents. Finally, we assess modulation of dopamine neurons by neuropeptides and peripheral peptidergic signals that occur with obesity or binge eating. We find that while decreased dopamine concentration is observed with obesity, there is inconsistency outside the human literature on the relationship between striatal D2 receptor expression and obesity. Finally, few studies have explored how orexigenic or anorexigenic peptides modulate dopamine neuronal activity or striatal dopamine in obese models. However, ghrelin modulation of dopamine neurons may be an important factor for driving binge feeding in rodents.

  20. 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)

  1. Do mast cells link obesity and asthma?

    Science.gov (United States)

    Sismanopoulos, N; Delivanis, D-A; Mavrommati, D; Hatziagelaki, E; Conti, P; Theoharides, T C

    2013-01-01

    Asthma is a chronic inflammatory disease of the lungs. Both the number of cases and severity of asthma have been increasing without a clear explanation. Recent evidence suggests that obesity, which has also been increasing alarmingly, may worsen or precipitate asthma, but there is little evidence of how obesity may contribute to lung inflammation. We propose that mast cells are involved in both asthma and obesity by being the target and source of adipocytokines, 'alarmins' such as interleukin-9 (IL-9) and interleukin-33 (IL-33), and stress molecules including corticotropin-releasing hormone (CRH) and neurotensin (NT), secreted in response to the metabolic burden. In particular, CRH and NT have synergistic effects on mast cell secretion of vascular endothelial growth factor (VEGF). IL-33 augments VEGF release induced by substance P (SP) and tumor necrosis factor (TNF) release induced by NT. Both IL-9 and IL-33 also promote lung mast cell infiltration and augment allergic inflammation. These molecules are also expressed in human mast cells leading to autocrine effects. Obese patients are also less sensitive to glucocorticoids and bronchodilators. Development of effective mast cell inhibitors may be a novel approach for the management of both asthma and obesity. Certain flavonoid combinations may be a promising new treatment approach.

  2. 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.

  3. Maternal obesity and pregnancy.

    Science.gov (United States)

    Johnson, S R; Kolberg, B H; Varner, M W; Railsback, L D

    1987-05-01

    We examined the risk of maternal obesity in 588 pregnant women weighing at least 113.6 kilograms (250 pounds) during pregnancy. Compared with a control group matched for age and parity, we found a significantly increased risk in the obese patient for gestational diabetes, hypertension, therapeutic induction, prolonged second stage of labor, oxytocin stimulation of labor, shoulder dystocia, infants weighing more than 4,000 grams and delivery after 42 weeks gestation. Certain operative complications were also more common in obese women undergoing cesarean section including estimated blood loss of more than 1,000 milliliters, operating time of more than two hours and wound infection postoperatively. These differences remained significant after controlling for appropriate confounding variables. We conclude that maternal obesity should be considered a high risk factor.

  4. Emotional Toll of Obesity

    Science.gov (United States)

    ... or the death of a parent or a divorce , and some children routinely overindulge in food. Discrimination There are other obesity-related repercussions that continue well into adolescence and beyond. Heavy teenagers and adults might face ...

  5. Childhood Obesity: Common Misconceptions

    Science.gov (United States)

    ... of childhood obesity. Yes, hypothyroidism (a deficit in thyroid secretion) and other rarer and more severe genetic and metabolic disorders (eg, Prader-Willi syndrome, Turner syndrome, Cushing syndrome) ...

  6. Obesity and Cancer Risk

    Science.gov (United States)

    ... GS. Inflammatory mechanisms in obesity. Annual Review of Immunology 2011; 29:415-445. [PubMed Abstract] Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. International Journal ...

  7. Zinc level and obesity

    Directory of Open Access Journals (Sweden)

    Doaa S.E. Zaky

    2013-01-01

    Conclusion Plasma zinc concentration in obese individuals showed an inverse relationship with the waist circumference and BMI as well as serum low-density lipoprotein-cholesterol and correlated positively with high-density lipoprotein.

  8. 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 ...

  9. Obesity in pregnancy

    DEFF Research Database (Denmark)

    Nøhr, Ellen Aagaard

    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......, if any, needs to be established in a randomized trial.Study of the selection to the Danish National Birth Cohort: Based on local data collections, independent of the DNBC, we investigated the impact of low participation on estimation of relative risks in a subpopulation of 49,751 eligible women of whom......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...

  10. 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...

  11. Chronobiological Effects on Obesity.

    Science.gov (United States)

    Bray, Molly S; Young, Martin E

    2012-03-01

    The development of obesity is the consequence of a multitude of complex interactions between both genetic and environmental factors. It has been suggested that the dramatic increase in the prevalence of obesity over the past 30 years has been the result of environmental changes that have enabled the full realization of genetic susceptibility present in the population. Among the many environmental alterations that have occurred in our recent history is the ever-increasing dyssynchrony between natural cycles of light/dark and altered patterns of sleep/wake and eating behavior associated with our "24-hour" lifestyle. An extensive research literature has established clear links between increased risk for obesity and both sleep deprivation and shift work, and our understanding of the consequences of such dyssynchrony at the molecular level is beginning to emerge. Studies linking alterations in cellular circadian clocks to metabolic dysfunction point to the increasing importance of chronobiology in obesity etiology.

  12. 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.

  13. Beyond gut microbiota: understanding obesity and type 2 diabetes.

    Science.gov (United States)

    Lau, Eva; Carvalho, Davide; Pina-Vaz, Cidália; Barbosa, José-Adelino; Freitas, Paula

    2015-01-01

    Obesity and type 2 diabetes are metabolic diseases that have reached epidemic proportions worldwide. Although their etiology is complex, both result from interplay between behaviour, environment and genetic factors. Within ambient determinants, human overall gut bacteria have been identified as a crucial mediator of obesity and its consequences. Gut microbiota plays a crucial role in gastro-intestinal mucosa permeability and regulates the fermentation and absorption of dietary polyssacharides, which may explain its importance in the regulation of fat accumulation and the resultant development of obesity-related diseases. The main objective of this review is to address the pathogenic association between gut microbiota and obesity and to explore related innovative therapeutic targets. New insights into the role of the small bowel and gut microbiota in diabetes and obesity may make possible the development of integrated strategies to prevent and treat these metabolic disorders.

  14. 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...... associated with obesity. METHODS: We conducted a systematic search for literature available before October 2015 in the PubMed and Scopus databases, focusing on the interplay between the gut microbiota, childhood obesity, and metabolism. RESULTS: The review discusses the potential role of the bacterial...... 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...

  15. CHOIS: enabling grid technologies for obesity surveillance and control.

    Science.gov (United States)

    Datta, Arun K; Jackson, Victoria; Nandkumar, Radha; Sproat, Jill; Zhu, Weimo; Krahling, Heidi

    2010-01-01

    CHOIS, the Child Health and Obesity Informatics System, is developed using open source portal technology with three-tiered Open Grid Services Architecture, an accepted standard for accessing Grid Computing and other services under Open Grid Collaborating Environments (OGCE). Its web application provides web based forms with 112 different fields to enter data ranging from demographic, height & weight for BMI, to genomic information. Automatic computation of BMI, BMI percentile and the risk of obesity alert are embedded into this system. After successful testing of the prototype, CHOIS is now ready to be used by the Illinois Department of Human Services (DHS) for obesity surveillance. This HIPAA & FERPA compliant secure system, integrating large databases in a high performance grid computing environment, enables school-nurse to collect data on school children and report statistical and surveillance information on BMI to identify those at-risk and obese for obesity prevention and intervention programs.

  16. Obesity and cancer

    OpenAIRE

    Calle, Eugenia E.

    2007-01-01

    Epidemiologic evidence associating obesity and cancer accumulated over last two decades pointing to potentially preventable forms of cancer disease. Observational prospective analyses point to breast and colon cancer as most influenced by obesity-linked lifestyle habits. Other tumor-types can comprise to this group as well (endometrium, esophagus, liver, stomach, thyroid, pancreas, and prostate cancer), according to epidemiological data, but with lesser level of certainty. Randomized studi...

  17. Zinc level and obesity

    OpenAIRE

    Doaa S.E Zaky; Eman A Sultan; Mahmoud F Salim; Rana S Dawod

    2013-01-01

    Background Obesity is a chronic condition that is associated with disturbances in the metabolism of zinc. Therefore, the aim of this study was to investigate the relationship between serum zinc level and different clinical and biochemical parameters in obese individuals. Patients and methods Twenty-four individuals with BMI more than 30 kg/m 2 and 14 healthy controls (BMI < 24 kg/m 2 ) were assessed for BMI and waist circumference using anthropometric measurements. Colorimetric tes...

  18. 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...

  19. 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.

  20. 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.

  1. Chronobiological Effects on Obesity

    OpenAIRE

    Bray, Molly S.; Young, Martin E.

    2012-01-01

    The development of obesity is the consequence of a multitude of complex interactions between both genetic and environmental factors. It has been suggested that the dramatic increase in the prevalence of obesity over the past 30 years has been the result of environmental changes that have enabled the full realization of genetic susceptibility present in the population. Among the many environmental alterations that have occurred in our recent history is the ever-increasing dyssynchrony between ...

  2. [Contraception and obesity].

    Science.gov (United States)

    Lobert, M; Pigeyre, M; Gronier, H; Catteau-Jonard, S; Robin, G

    2015-11-01

    The prevalence of obesity is increasing massively over several decades in industrialized countries. Obese women are sexually active but they use fewer contraceptive methods and are at high risk of unintended pregnancy. In addition, obesity is an important risk factor for venous thromboembolism events and arterial thrombosis (myocardial infarction and ischemic stroke). All of these data are to be considered in choosing a contraceptive method for obese women. Except depot medroxyprogesterone acetate injection, the progestin-only contraceptives (progestin only pills and etonogestrel subdermal implant) and the intra-uterine devices are the preferred contraceptive methods in obese women. The combined estrogen-progestin contraceptives (pill, patch and vaginal ring) may be proposed in very strict conditions (no other associated vascular risk factor). Obesity does not increase the risk of failure of most contraceptive methods. Bariatric surgery is a complex situation. It requires to program a possible pregnancy and contraception is needed for several months. Some bariatric surgical techniques such as by-pass can induce gastrointestinal malabsorption. In this situation, all oral contraceptives are not recommended because of a higher risk of failure.

  3. Contraception in Obese Women

    Directory of Open Access Journals (Sweden)

    Merki Feld G

    2015-01-01

    Full Text Available Today obesity is an epidemic. Within Europe the prevalence of obesity is 20–30% with a tendency to increase further. Obesity is associated with severe complications like diabetes mellitus, cardiovascular disease increased risk for venous thromboembolism (VTE and metabolic syndrome. Especially availability of efficient methods which do not further enhance the cardiovascular and thromboembolic risk in obese women is an important point. Using contraception to prevent unwanted pregnancies is recommended to all women whatever their weight, as it reduces the risks of unplanned pregnancy, which is higher in women with overweight. Progestin-only contraceptives and IUDs have no or minimal metabolic effects and are first choices options, also it has to be taken in account that oral progestins and the implant might have lower efficacy in very obese women. CHC are associated with a higher risk for VTE in obese women,but should be used if other methods are not acceptable. A long-cycle or use of preparations with 30 mcg EE can contribute to improve efficacy.

  4. [Inequality, poverty and obesity].

    Science.gov (United States)

    Ferreira, Vanessa Alves; Silva, Aline Elizabeth; Rodrigues, Chrystiellen Ayana Aparecida; Nunes, Nádia Lúcia Almeida; Vigato, Tássia Cassimiro; Magalhães, Rosana

    2010-06-01

    National studies have been demonstrating the positive relationship among inequality, poverty and obesity revealing the singularities and complexity of the nutritional transition in Brazil. In this direction, the women constitute a vulnerable group to the dynamics of the obesity in the poverty context. Such fact imposes the theoretical deepening and the accomplishment of researches that make possible a larger approach with the phenomenon in subject. In this perspective, the study analyzed the daily life of poor and obese women, users of basic units of health of the city of Diamantina, Vale do Jequitinhonha, Minas Gerais State. The results revealed the complex relationship between feminine obesity and poverty. The cultural and material aspects of life, as well as the different feeding and body conceptions that demonstrated to be fundamental elements for the analysis of the multiple faces of the obesity among the investigated group. Facing these results it is appropriate to encourage public policies that promote equity widening the access of those groups to the main resources for the prevention and combat of obesity.

  5. Psoriasis and Obesity

    Directory of Open Access Journals (Sweden)

    Mehmet Ali Gürer

    2012-03-01

    Full Text Available In recent years, it has been thought that a strong association exists between metabolic syndrome, specifically obesity, and psoriasis. Obesity is a multifactorial disease affected by both genetic and environmental factors. Adipokines (e.g. leptin secreted by the adipose tissue are believed to play a role in the pathogenesis of psoriasis. The main role of leptin is to adjust metabolism by controlling appetite. Serum leptin levels in patients with severe and moderate psoriasis were found to be higher than in normal control groups. In many similar studies, leptin secretion has been found to stimulate keratinocyte proliferation, which is one of the characteristics of psoriasis. Although many studies showed increased prevalence of obesity in psoriasis patients, few others reported development of obesity in psoriasis patients. Additionally, obesity was found to affect treatment responses not only in classical systemic/topical treatment approaches in psoriasis, but also in newer biological treatments. Overall, increasing epidemiological evidence suggests strong association between obesity and psoriasis, increase in serum leptin levels is thought to have a major role, and weight loss may have significant impact on response to treatment.

  6. [Sleep/wake cycle, circadian disruption and the development of obesity].

    Science.gov (United States)

    Masaki, Takayuki

    2012-07-01

    It is increasingly recognized that obesity is an important health problem. The mechanisms that underlie obesity have not been fully elucidated, and effective therapeutic approaches are currently of general interest. Recent studies have provided evidence that circadian clock is a crucial factor in the development of obesity and related metabolic disease. Genetic disruption of clock genes in mice displayed metabolic dysfunctions of specific tissues at distinct phases of the sleep/wake cycle. In addition, circadian desynchrony, a characteristic of shift work and short sleep, are associated with obesity in human. Here, I describe the advances in understanding the interrelationship among circadian disruption, sleep deprivation and obesity.

  7. [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.

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

    Science.gov (United States)

    Pretlow, Robert A; Corbee, Ronald J

    2016-09-01

    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 short-term but poor long-term results. New strategies are needed. A novel theory posits that obesity in pets and children is due to 'treats' and excessive meal amounts given by the 'pet-parent' and child-parent to obtain affection from the pet/child, which enables 'eating addiction' in the pet/child and results in parental 'co-dependence'. Pet-parents and child-parents may even become hostage to the treats/food to avoid the ire of the pet/child. Eating addiction in the pet/child also may be brought about by emotional factors such as stress, independent of parental co-dependence. An applicable treatment for child obesity has been trialled using classic addiction withdrawal/abstinence techniques, as well as behavioural addiction methods, with significant results. Both the child and the parent progress through withdrawal from specific 'problem foods', next from snacking (non-specific foods) and finally from excessive portions at meals (gradual reductions). This approach should adapt well for pets and pet-parents. Pet obesity is more 'pure' than child obesity, in that contributing factors and treatment points are essentially under the control of the pet-parent. Pet obesity might thus serve as an ideal test bed for the treatment and prevention of child obesity, with focus primarily on parental behaviours. Sharing information between the fields of pet and child obesity would be mutually beneficial.

  9. Survey of American food trends and the growing obesity epidemic.

    Science.gov (United States)

    Shao, Qin; Chin, Khew-Voon

    2011-06-01

    The rapid rise in the incidence of obesity has emerged as one of the most pressing global public health issues in recent years. The underlying etiological causes of obesity, whether behavioral, environmental, genetic, or a combination of several of them, have not been completely elucidated. The obesity epidemic has been attributed to the ready availability, abundance, and overconsumption of high-energy content food. We determined here by Pearson's correlation the relationship between food type consumption and rising obesity using the loss-adjusted food availability data from the United States Department of Agriculture (USDA) Economic Research Services (ERS) as well as the obesity prevalence data from the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health and Nutrition Examination Survey (NHANES) at the Centers for Disease Control and Prevention (CDC). Our analysis showed that total calorie intake and consumption of high fructose corn syrup (HFCS) did not correlate with rising obesity trends. Intake of other major food types, including chicken, dairy fats, salad and cooking oils, and cheese also did not correlate with obesity trends. However, our results surprisingly revealed that consumption of corn products correlated with rising obesity and was independent of gender and race/ethnicity among population dynamics in the U.S. Therefore, we were able to demonstrate a novel link between the consumption of corn products and rising obesity trends that has not been previously attributed to the obesity epidemic. This correlation coincides with the introduction of bioengineered corns into the human food chain, thus raising a new hypothesis that should be tested in molecular and animal models of obesity.

  10. Autonomic nervous system dysfunction in obesity and Prader-Willi syndrome: current evidence and implications for future obesity therapies.

    Science.gov (United States)

    Haqq, A M; DeLorey, D S; Sharma, A M; Freemark, M; Kreier, F; Mackenzie, M L; Richer, L P

    2011-08-01

    The autonomic nervous system (ANS) controls essential functions like breathing, heart rate, digestion, body temperature and hormone levels. Evidence suggests that ANS dysfunction is associated with adult and childhood obesity and plays a role in the distribution of total body fat and the development of obesity-related complications in humans. This review summarizes our current understanding of ANS involvement in the pathogenesis of obesity and Prader-Willi syndrome. Available evidence of ANS dysfunction in the control of energy balance is limited and, in some cases, contradictory. Further investigation in this area is warranted in order to better understand the important contributions of the ANS to regulation of body fat, development of obesity and its comorbidities. Results from these studies will guide the development of novel obesity therapeutics targeting specific ANS dysfunction.

  11. 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

    Elevated free fatty acids (FFA) are implicated with insulin resistance at the cellular level. However, the contribution of whole body lipid kinetics to FFA-induced insulin resistance is not well understood, and the effect of exercise and diet on this metabolic defect is not known. We investigated.......8 +/- 1.8 kg/m(2)) or a eucaloric (n = 8; 67 +/- 2 yr, 35.3 +/- 2.1 kg/m(2)) diet and aerobic exercise (1 h/day at 65% of maximal oxygen uptake) regimen. Lipid kinetics ([1-(14)C]palmitate) were assessed throughout a 7-h, 40 mU x m(-2) x min(-1) hyperinsulinemic euglycemic clamp, during which insulin...... 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...

  12. Standardization of model to induce obesity in rats

    Directory of Open Access Journals (Sweden)

    Gipsis Suárez Román

    2013-10-01

    Full Text Available Background: Obesity is a risk factor for multiple diseases. There are various rat models to induce this condition. Genetic models and diet-induced obesity are expensive. Within the models of hypothalamic obesity, there is one achieved by the administration of monosodium glutamate during the neonatal period. This substance is not expensive and causes the major metabolic alterations observed in human obesity. Objective: to select an appropriate treatment scheme to induce obesity with monosodium glutamate during neonatal period. Methods: monosodium glutamate was administered to Wistar rats during the neonatal period, using three different treatment schemes (with five, seven and ten doses of 4mg/g/day through two routes of administration: subcutaneous and intraperitoneal routes. Controls were administered 0.9% sodium chloride. To establish the diagnosis of obesity, the following variables were measured at 90 days: weight, snout-anus length and Lee index. Results: with all treatment schemes tested, snout-anus length was statistically different between the group treated with monosodium glutamate and the controls group. 100% of the rats that reached adulthood injected with monosodium glutamate was obese. Conclusion: the scheme of five doses of monosodium glutamate, applied subcutaneously on alternate days, was selected as obesity is obtained with less handling and lower percentage of neonatal deaths.

  13. Scale-free correlations in the geographical spreading of obesity

    Science.gov (United States)

    Gallos, Lazaros; Barttfeld, Pablo; Havlin, Shlomo; Sigman, Mariano; Makse, Hernan

    2012-02-01

    Obesity levels have been universally increasing. A crucial problem is to determine the influence of global and local drivers behind the obesity epidemic, to properly guide effective policies. Despite the numerous factors that affect the obesity evolution, we show a remarkable regularity expressed in a predictable pattern of spatial long-range correlations in the geographical spreading of obesity. We study the spatial clustering of obesity and a number of related health and economic indicators, and we use statistical physics methods to characterize the growth of the resulting clusters. The resulting scaling exponents allow us to broadly classify these indicators into two separate universality classes, weakly or strongly correlated. Weak correlations are found in generic human activity such as population distribution and the growth of the whole economy. Strong correlations are recovered, among others, for obesity, diabetes, and the food industry sectors associated with food consumption. Obesity turns out to be a global problem where local details are of little importance. The long-range correlations suggest influence that extends to large scales, hinting that the physical model of obesity clustering can be mapped to a long-range correlated percolation process.

  14. 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

    2015-03-13

    Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65% to 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, and (3) increased sympathetic nervous system activity. Activation of the renin-angiotensin-aldosterone system is likely due, in part, to renal compression, as well as sympathetic nervous system activation. However, obesity also causes mineralocorticoid receptor activation independent of aldosterone or angiotensin II. The mechanisms for sympathetic nervous system activation in obesity have not been fully elucidated but may 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 mellitus, and inflammation. Unless effective antiobesity drugs are developed, the effect 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.

  15. 自噬在肥胖中的研究进展%Research advance in autophagy in obesity

    Institute of Scientific and Technical Information of China (English)

    王李洁; 杨怡; 孙永红; 郑筱祥

    2012-01-01

    Obesity is a harmful nutritional metabolic disorder to human health. Autophagy is a catabolic mechanism whereby cells degrade intracellular substances. Recent studies show that autophagy was closely correlated with insulin resistance, fat composing, and lipid droplet and triglyceride accumulation. Here, we review the association between autophagy and obesity, which may provide theoretical and experimental evidence for prevention of obesity and related diseases.

  16. Obesity and Developmental Functioning among Children Aged 2-4 Years. National Poverty Center Working Paper Series #08-07

    Science.gov (United States)

    Cawley, John; Spiess, C. Katharina

    2008-01-01

    In developed countries, obesity tends to be associated with worse labor market outcomes. One possible reason is that obesity leads to less human capital formation early in life. This paper investigates the association between obesity and the developmental functioning of children at younger ages (2-4 years) than ever previously examined. Data from…

  17. Comprehensive Map of Molecules Implicated in Obesity.

    Directory of Open Access Journals (Sweden)

    Jaisri Jagannadham

    Full Text Available Obesity is a global epidemic affecting over 1.5 billion people and is one of the risk factors for several diseases such as type 2 diabetes mellitus and hypertension. We have constructed a comprehensive map of the molecules reported to be implicated in obesity. A deep curation strategy was complemented by a novel semi-automated text mining system in order to screen 1,000 full-length research articles and over 90,000 abstracts that are relevant to obesity. We obtain a scale free network of 804 nodes and 971 edges, composed of 510 proteins, 115 genes, 62 complexes, 23 RNA molecules, 83 simple molecules, 3 phenotype and 3 drugs in "bow-tie" architecture. We classify this network into 5 modules and identify new links between the recently discovered fat mass and obesity associated FTO gene with well studied examples such as insulin and leptin. We further built an automated docking pipeline to dock orlistat as well as other drugs against the 24,000 proteins in the human structural proteome to explain the therapeutics and side effects at a network level. Based upon our experiments, we propose that therapeutic effect comes through the binding of one drug with several molecules in target network, and the binding propensity is both statistically significant and different in comparison with any other part of human structural proteome.

  18. Factors associated with childhood obesity.

    Science.gov (United States)

    Dietz, W

    1991-01-01

    Childhood obesity is associated with host factors that enhance susceptibility and environmental factors that increase food intake and decrease energy expenditure. Obese children underreport food intake and probably consume more food to maintain their weight at increased levels. Prevalence of obesity is related to family variables, including parental obesity, family size and age, and socioeconomic status. Television viewing is strongly associated with the prevalence of obesity through its impact on food intake and activity. How these environmental variables are behaviorally interrelated to the genesis of obesity is unclear.

  19. 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....

  20. Can We Prevent Obesity-Related Metabolic Diseases by Dietary Modulation of the Gut Microbiota?

    Science.gov (United States)

    Brahe, Lena K; Astrup, Arne; Larsen, Lesli H

    2016-01-01

    Obesity increases the risk of type 2 diabetes, cardiovascular diseases, and certain cancers, which are among the leading causes of death worldwide. Obesity and obesity-related metabolic diseases are characterized by specific alterations in the human gut microbiota. Experimental studies with gut microbiota transplantations in mice and in humans indicate that a specific gut microbiota composition can be the cause and not just the consequence of the obese state and metabolic disease, which suggests a potential for gut microbiota modulation in prevention and treatment of obesity-related metabolic diseases. In addition, dietary intervention studies have suggested that modulation of the gut microbiota can improve metabolic risk markers in humans, but a causal role of the gut microbiota in such studies has not yet been established. Here, we review and discuss the role of the gut microbiota in obesity-related metabolic diseases and the potential of dietary modulation of the gut microbiota in metabolic disease prevention and treatment.

  1. Can we prevent obesity-related metabolic diseases by dietary modulation of the gut microbiota?

    DEFF Research Database (Denmark)

    Brahe, Lena Kirchner; Astrup, Arne; Larsen, Lesli Hingstrup

    2016-01-01

    Obesity increases the risk of type 2 diabetes, cardiovascular diseases, and certain cancers, which are among the leading causes of death worldwide. Obesity and obesity-related metabolic diseases are characterized by specific alterations in the human gut microbiota. Experimental studies with gut...... microbiota transplantations in mice and in humans indicate that a specific gut microbiota composition can be the cause and not just the consequence of the obese state and metabolic disease, which suggests a potential for gut microbiota modulation in prevention and treatment of obesity-related metabolic...... diseases. In addition, dietary intervention studies have suggested that modulation of the gut microbiota can improve metabolic risk markers in humans, but a causal role of the gut microbiota in such studies has not yet been established. Here, we review and discuss the role of the gut microbiota in obesity...

  2. Effects of Food Restriction on Fat Metabolism Index of Monosodium Glutamate in Obese Rats and Human%限食对谷氨酸钠肥胖大鼠及人体肥胖代谢指标的影响

    Institute of Scientific and Technical Information of China (English)

    关真民; 王慧; 程俊美; 鹿勇

    2013-01-01

    Investigation has been conducted to observe the effect of short-term food restriction on fat metabolism index of obesity and rat by means not only of animal experiment:glutamate obese rats have been divided into control group and food restriction group,and the Lee index weight,fat index and glycerin three greases' change of the two groups observed,but also of human experiment:the subjects were 21women,aged 22-45 years old.Limited food have been given seven days of fasting,first days for the buff er,the first 2-6 days for fasting days,seventh days for the restoration of day,food restriction for first days of acupuncture points and massage.Observation has been done on the body fat,body fat percentage,body weight,BMI and the change of waist circumference before and after food restriction.Results show that glutamate obese rats with food restriction group's weight,Lee index,fat index and glycerin three greases is markedly decreased with a very significant difference (p<0.01) compared with the control group; 21 subjects in the dietary restriction of body fat,body fat percentage and waist circumference are also significantly decreased and had significant difference (p<0.05),and the body weight and BMI decreased with a very significant difference (p<0.01).It is concluded that food restriction therapy has im portant significance for obesity treatment and prevention of complications.%目的 观察短期限食对肥胖人群及大鼠脂肪代谢指标的影响.方法 动物实验:将谷氨酸钠肥胖大鼠分为对照组和限食组,并分别观察两组体重、Lee指数、脂肪指数和甘油三酯的变化;人体实验:受试者为21名女性,年龄22~45岁.限食者均限食7天,第1天为缓冲日,第2~6天为禁食日,第7天为恢复日.观察限食前后体脂、体脂百分率、体重、BMI和腰围的变化.结果 谷氨酸钠肥胖大鼠限食组体重、Lee指数、脂肪指数和甘油三酯与对照组相比明显下降,

  3. Obesity and the obesity paradox in heart failure.

    Science.gov (United States)

    Gupta, Pritha P; Fonarow, Gregg C; Horwich, Tamara B

    2015-02-01

    Obesity has reached epidemic proportions in the general population and is associated with an increased risk for the development of new-onset heart failure (HF). However, in acute and chronic HF, overweight and mild to moderate obesity is associated with substantially improved survival compared with normal weight. This phenomenon has been termed the "obesity paradox" in HF. The majority of data pertaining to the obesity paradox identifies obesity with body mass index; however, the reliability of this method has been questioned. Newer studies have explored the use of other measures of body fat and body composition, including waist circumference, waist-to-hip ratio, skinfold thickness, and bioelectrical impedance analysis of body composition. The relationship between the obesity paradox and cardiorespiratory fitness in HF is also discussed in this review, and we explore the various potential explanations for the obesity paradox and summarize the current evidence and guidelines for intentional weight loss treatments for HF in the obese population.

  4. Obesity and asthma: co-morbidity or causal relationship?

    Science.gov (United States)

    van Huisstede, A; Braunstahl, G J

    2010-09-01

    There is substantial evidence that obesity and asthma are related. "Obese asthma" may be a unique phenotype of asthma, characterized by decreased lung volumes, greater symptoms for a given degree of lung function impairment, destabilization or lack of asthma control, lack of eosinophilic inflammation and a different response to controller medication. Whether this relationship between obesity and asthma is causal or represents co-morbidity due to other factors is unclear. In previous reviews concerning the relationship between obesity and asthma, five hypotheses were put forth. One of these hypotheses is that a low grade systemic inflammation caused by adipokines from the fat tissue causes or enhances bronchial inflammation. In animal models, there is an increasing amount of evidence for the role of adipokines derived from fat tissue in the relationship between obesity and asthma. The data are conflicting in humans. Since obesity is a component of the metabolic syndrome and the metabolic syndrome is also a form of systemic inflammation, it is to be expected that there is a relationship between metabolic syndrome and asthma. The few data that are available show that there is no relationship between metabolic syndrome and asthma, but there is one between the metabolic syndrome and asthma-like symptoms. Further research is needed to confirm the relationship between obesity and asthma in humans, where a rigorous approach in the diagnosis of asthma is essential.

  5. Dysregulation of the endocannabinoid system in obesity.

    Science.gov (United States)

    Engeli, S

    2008-05-01

    An activation of the endocannabinoid system (ECS) in obesity with increased concentrations of endocannabinoids in several tissues and in the circulation is described in this review. This increased availability of endocannabinoids might stimulate cannabinoid receptors in a pathophysiological manner. The successful use of the cannabinoid receptor CB(1) inverse agonists rimonabant and taranabant for weight loss and the treatment of obesity-associated metabolic disorders might well be through blocking this overstimulation of cannabinoid receptors. At present, no single mechanism has been identified that explains the increased bioavailability of endocannabinoids in obesity. Both increased synthesis and decreased degradation appear to operate in a species- and tissue-dependent manner, but many pieces of the puzzle still need to be collected. For example, most data show decreased fatty acid amide hydrolase (FAAH) expression and/or activity as a result of obesity or high-fat intake, but the endocannabinoid predominantly increased in tissues is 2-arachidonoylglycerol (2-AG), which is not degraded by FAAH in vivo. Furthermore, the influence of dietary fatty acids on the synthesis of endocannabinoids needs to be studied in much more detail. Although weight loss does not seem to influence activation of the endocannabinoid system (ECS) in human obesity, suggesting an underlying mechanisms independent of body weight, no such mechanism at the genetic level has yet been identified either. Thus, activation of the ECS is a hallmark of abdominal obesity, and explains the success of pharmacological CB(1) blockade, but serious attempts have to be made to clarify the underlying mechanisms of this activation.

  6. Obesity: epigenetic aspects.

    Science.gov (United States)

    Kaushik, Prashant; Anderson, James T

    2016-06-01

    Epigenetics, defined as inheritable and reversible phenomena that affect gene expression without altering the underlying base pair sequence has been shown to play an important role in the etiopathogenesis of obesity. Obesity is associated with extensive gene expression changes in tissues throughout the body. Epigenetics is emerging as perhaps the most important mechanism through which the lifestyle-choices we make can directly influence the genome. Considerable epidemiological, experimental and clinical data have been amassed showing that the risk of developing disease in later life is dependent on early life conditions, mainly operating within the normative range of developmental exposures. In addition to the 'maternal' interactions, there has been increasing interest in the epigenetic mechanisms through which 'paternal' influences on offspring development can be achieved. Nutrition, among many other environmental factors, is a key player that can induce epigenetic changes not only in the directly exposed organisms but also in subsequent generations through the transgenerational inheritance of epigenetic traits. Overall, significant progress has been made in the field of epigenetics and obesity and the first potential epigenetic markers for obesity that could be detected at birth have been identified. Fortunately, epigenetic phenomena are dynamic and rather quickly reversible with intensive lifestyle changes. This is a very promising and sustainable resolution to the obesity pandemic.

  7. [Childhood obesity and dyslipidemia].

    Science.gov (United States)

    Gómez-Díaz, Rita Angélica; Wacher-Rodarte, Niels H

    2014-01-01

    Screening and treatment of plasma lipid abnormalities secondary to obesity are among the interventions that should be implemented in children who are overweight or obese, in order to prevent a cardiovascular event. Dyslipidemias are a group of asymptomatic diseases that are commonly caused by abnormal levels of lipoproteins in blood; they are a comorbidity that is commonly related to obesity, without considering the age of the patient. Among dyslipidemias, hypertriglyceridemia has the highest prevalence. The etiology of the dyslipidemia should be identified; it allows the proper selection of therapy for the patients and their family. The goal is the prevention of cardiovascular complications. Reduced caloric intake and a structured physical activity plan should be considered for initial treatment for all the overweight and obese patients. For adherence to treatment to be successful, the participation of the primary care physician and a multidisciplinary team is required. With treatment, the risks and complications can be reduced. The participation of a specialist in handling the pediatric obese patient with dyslipidemia should be limited to severe cases or those at risk for having pancreatitis.

  8. Dietary treatments of obesity.

    Science.gov (United States)

    Bennett, W

    1987-01-01

    Dietary treatment of obesity is based on one or another of two premises: that the obese eat too much or that they eat the wrong things. The first is a tautology lacking explanatory power. The second is a meaningful and promising hypothesis but has yet to be effectively applied. At present, virtually all outpatient treatments of obesity, including behavior modification, are based on the first premise and consist of strategies for reducing the subject's caloric intake. Most such interventions produce short-term weight loss. Regain after the end of treatment remains the usual outcome. A survey of studies published in the period 1977-1986 and reporting on dietary or behavioral treatment of obesity reveals that the maximum percentage of body weight lost is, on average, 8.5 percent--no different from the value, 8.9%, in similar studies from 1966-1976, as reviewed by Wing and Jeffery. The principal determinant of success in such programs appears to be the intake weight of the subjects: the higher the intake weight, the more successful the intervention will appear to be. The goals and research methods of studies on dietary treatments for obesity are overdue for ethical as well as scientific reevaluation. The same may be said for the numerous programs providing such treatment outside the context of research.

  9. Familial obesity as a predictor of child obesity

    Directory of Open Access Journals (Sweden)

    Mirilov Jelena

    2005-01-01

    Full Text Available Introduction Studies carried out in various parts of the world indicate that family obesity significantly affects the incidence of obesity in children. This is especially a characteristic of children whose both parents are obese. Material and methods The study was conducted using a polling method. Questionnaires were filled out by parents and brothers and sisters, including their body height and weight. The collected data served as the basis for assessing the family nutritional status. Results Statistical analysis of the results showed that obese children frequently have obese parents, brothers and sisters in regard to normal-weight children. Differences are statistically significant in relation to fathers (r=0.043, i.e. statistically obese schoolchildren have more frequently obese fathers than those of normal nutritional status. Other differences could not be considered significant (p > 0.05. Discussion Obese children have more often obese parents, brothers and sisters than normal-weight children. It was found that the nutritional status of moderately and extremely obese children was quite different from that of normal-weight children and that there was a statistically significant dependence between the nutritional status of children and their fathers. Conclusion This research showed that family obesity is a potential contributing factor to obesity of schoolchildren.

  10. Severe Obesity and Heart Failure

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_161011.html Severe Obesity and Heart Failure Study sees link even without ... 2016 FRIDAY, Sept. 16, 2016 (HealthDay News) -- Severe obesity appears to be an independent risk factor for ...

  11. Understanding Adult Overweight and Obesity

    Science.gov (United States)

    ... resources ​​. Alternate Language URL Understanding Adult Overweight and Obesity Page Content How can I tell if I ... type 2 diabetes. [ Top ] How are overweight and obesity treated? The best way to control your weight ...

  12. Childhood Obesity for Pediatric Gastroenterologists

    Science.gov (United States)

    Huang, Jeannie S.; Barlow, Sarah E.; Quiros-Tejeira, Ruben E.; Scheimann, Ann; Skelton, Joseph; Suskind, David; Tsai, Patrika; Uko, Victor; Warolin, Joshua P.; Xanthakos, Stavra A.

    2014-01-01

    Obesity in childhood is one of the major health issues in pediatric health care today. As expected, the prevalence of obesity-related comorbidities has risen in parallel with that of obesity. Consultation regarding these concomitant diseases and subsequent management by subspecialists, including pediatric gastroenterologists, is now common and has resulted in obesity being recognized as a chronic disease requiring coordination of care. Although medications and even surgery may provide effective, though often temporary, treatments for obesity and its comorbidities, behavioral interventions addressing healthy dietary and physical activity habits remain a mainstay in the obesity treatment paradigm. Therefore, the issue of weight management must be addressed by both general practitioner and subspecialist alike. In this report, we review select aspects of pediatric obesity and obesity-related management issues because it relates in particular to the field of pediatric gastroenterology and hepatology. PMID:23282941

  13. Osteoarthritis and obesity: Experimental models

    OpenAIRE

    Gabay, Odile; Hall, David J.; Berenbaum, Francis; Henrotin, Yves; Sanchez, Christelle

    2008-01-01

    Osteoarthritis (OA) is a multifactorial disease. Different risk factors have been identified such as aging and obesity and different models have been used to study the impact of obesity and overweight in this pathology.

  14. Etiology of obesity: two "key issues" and other emerging factors

    OpenAIRE

    Lluis Serra-Majem; Inmaculada Bautista-Castaño

    2013-01-01

    The current obesity epidemic is known to have coincided with profound societal changes involving both physical activity levels and food consumption patterns as well as demographic and cultural changes affecting the conduct of human beings in various ways. On the other hand, obesity is a complex and multifactorial chronic disease that usually becomes manifest in childhood and adolescence. Its origin is a genetic and environmental interchange, of which environmental or behavioral factors play t...

  15. 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....

  16. Dissolve energy obesity by energy diet

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Heum [Sunmoon University, Asan (Korea)

    2000-07-01

    Every organism takes needed materials or energy from outside and excretes unessential things to outside. This is called a metabolism or energy metabolism. Calculating the amount of energy consumed by human in the world by converting to the amount of metabolism of an animal to survive, the weight of a human being is corresponding to an animal with a weigh of 40 ton. Human beings can find a solution to dissolve energy obesity or can maintain a massive status by finding a new energy source in the universe.

  17. Sleep debt and obesity.

    Science.gov (United States)

    Bayon, Virginie; Leger, Damien; Gomez-Merino, Danielle; Vecchierini, Marie-Françoise; Chennaoui, Mounir

    2014-08-01

    Short sleep duration has been shown to be associated with elevated body mass index (BMI) in many epidemiological studies. Several pathways could link sleep deprivation to weight gain and obesity, including increased food intake, decreased energy expenditure, and changes in levels of appetite-regulating hormones, such as leptin and ghrelin. A relatively new factor that is contributing to sleep deprivation is the use of multimedia (e.g. television viewing, computer, and internet), which may aggravate sedentary behavior and increase caloric intake. In addition, shift-work, long working hours, and increased time commuting to and from work have also been hypothesized to favor weight gain and obesity-related metabolic disorders, because of their strong link to shorter sleep times. This article reviews the epidemiological, biological, and behavioral evidence linking sleep debt and obesity.

  18. Exercise and obesity.

    Science.gov (United States)

    Okay, Douglas M; Jackson, Paul V; Marcinkiewicz, Marek; Papino, M Novella

    2009-06-01

    Obesity and overweight are linked to a wide range of medical conditions, such as hypertension, diabetes mellitus, osteoarthritis, obstructive sleep apnea, and coronary artery disease. Overweight and obese patients who are unable to lose weight with diet alone can benefit from well-structured exercise. Potentially, an individual exercise prescription can become one of the most important components of an obesity treatment program, along with an appropriate diet. Short-term (exercise combined with appropriate diet and counseling can produce a significant weight loss. No consensus exists on the amount of physical activity necessary to maintain the weight loss achieved during a short-term intervention. Long-term intervention is frequently influenced by weight regain related to complex interactions between physiologic and psychosocial factors.

  19. Medical consequences of obesity.

    Science.gov (United States)

    Lawrence, Victor J; Kopelman, Peter G

    2004-01-01

    The obese are subject to health problems directly relating to the carriage of excess adipose tissue. These problems range from arthritis, aches and pains, sleep disturbance, dyspnea on mild exertion, and excessive sweating to social stigmatization and discrimination, all of which may contribute to low quality of life and depression (Table 1). The most serious medical consequences of obesity are a result of endocrine and metabolic changes, most notably type 2 diabetes mellitus, cardiovascular disease, and increased risk of cancer. Not all obesity comorbidities are fully reversed by weight loss. The degree and duration of weight loss required may not be achievable by an individual patient. Furthermore, "weight cycling" may be more detrimental to both physical and mental health than failure to achieve weight loss targets with medical and lifestyle advice.

  20. Genetic obesity syndromes.

    Science.gov (United States)

    Goldstone, Anthony P; Beales, Philip L

    2008-01-01

    There are numerous reports of multi-system genetic disorders with obesity. Many have a characteristic presentation and several, an overlapping phenotype indicating the likelihood of a shared common underlying mechanism or pathway. By understanding the genetic causes and functional perturbations of such syndromes we stand to gain tremendous insight into obesogenic pathways. In this review we focus particularly on Bardet-Biedl syndrome, whose molecular genetics and cell biology has been elucidated recently, and Prader-Willi syndrome, the commonest obesity syndrome due to loss of imprinted genes on 15q11-13. We also discuss highlights of other genetic obesity syndromes including Alstrom syndrome, Cohen syndrome, Albright's hereditary osteodystrophy (pseudohypoparathyroidism), Carpenter syndrome, MOMO syndrome, Rubinstein-Taybi syndrome, cases with deletions of 6q16, 1p36, 2q37 and 9q34, maternal uniparental disomy of chromosome 14, fragile X syndrome and Börjeson-Forssman-Lehman syndrome.