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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The renin-angiotensin system with its active metabolite angiotensin (Ang) II has been related not only to hypertension but also to obesity and insulin resistance. Recent evidence obtained in vitro suggests that the type 2 Ang II receptor (AT2R) mediates the trophic action of Ang II on adipocyte differentiation and lipogenesis. We used AT2R(y/-) mice to delineate a potential role of AT2R in adipose tissue development and metabolism. AT2R(y/-) mice had a normal adiposity but displayed a striking adipose tissue phenotype characterized by small adipocytes and an increase in cell number. In muscle, the expression of several genes involved in lipid metabolism, including fatty acid translocase, uncoupling protein-3, peroxisome proliferator-activated receptors (alpha, delta), and carnitine palmitoyl transferase-1, was increased in AT2R-deficient mice. In response to high-fat feeding, these mice were protected against obesity and obesity-related glucose intolerance, as assessed by glucose tolerance tests. Moreover, lipid oxidation assessed by indirect calorimetry was higher in AT2R-deficient mice than in wild-type mice, irrespective of the diet. This suggests that AT2R-dependent signaling exerts a direct or indirect negative control on lipid utilization in muscles. These data support the idea that AT2R-dependent Ang II signaling increases adipose cell mass and glucose intolerance and thus could participate to the deleterious effects of a high-fat diet.
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PMID:Deletion of the angiotensin type 2 receptor (AT2R) reduces adipose cell size and protects from diet-induced obesity and insulin resistance. 1579 37

Obesity is a multidisciplinary area, the 'biology' of which encompasses: (1) the fundamental mechanisms of energy balance and its regulation; (2) the biological basis for the development of obesity; (3) adipose tissue function; (4) the biological description of the obese state; (5) the pathological consequences of obesity; (6) the physiological basis for treatment strategies. At a mechanistic level, important developments in recent years include the identification of novel neuroendocrine factors in the control of appetite (such as cocaine- and amphetamine-regulated transcript, the orexins, the endocannabinoids) and the discovery of new peripheral signals (such as leptin, ghrelin). Despite the identification of additional uncoupling proteins (UCP2, UCP3), mitochondrial uncoupling in brown adipose tissue through UCP1 remains the only major mechanism for adaptive thermogenesis. White adipose tissue (WAT) has now moved centre stage in energy balance and obesity research, and there are three main reasons: (1) it is the organ which defines obesity; (2) it is the source of a critical endocrine signal in the control of body weight; (3) it secretes a range of diverse protein factors, termed adipokines, some of which are directly implicated in the pathologies associated with obesity. WAT is now recognised as a key endocrine organ, communicating both with the brain and peripheral tissues through the adipokines. Obesity is characterised by mild inflammation, and WAT may be the main locus of the inflammatory state, producing cytokines, chemokines, acute-phase proteins and angiogenic factors. It has been suggested that inflammation in obesity is principally an adaptive response to hypoxia in clusters of adipocytes within the expanding adipose mass.
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PMID:The biology of obesity. 1587 20

Metabolic energy expenditure negatively regulates energy balance. Metabolic and catabolic pathways contribute to energy expenditure. Catabolic pathways split C-containing molecules into small molecules and generate reduced coenzymes and ATP. For a given amount of substrate, any increase in energy expenditure requires either increased ATP hydrolysis or decreased ATP synthesis. In skeletal muscles substrate utilisation is coupled to ATP production, whereas ATP hydrolysis is activated during physical exercise and increases energy expenditure. In brown adipose tissue activation of cells during exposure to cold increases substrate utilisation in such a way that glucose and fatty acid oxidation detach from the orthodox coupling to ATP synthesis and result in thermogenesis. The unique mechanism of uncoupling respiration that occurs in brown adipocyte mitochondria represents an attractive strategy for promoting energy expenditure and decreasing the fat content of the body. Moreover, ectopic expression of brown fat uncoupling protein (UCP) 1 in mouse skeletal muscle and induction of UCP1 in mouse or human white adipocytes promote fatty acid oxidation and resistance to obesity. In normal conditions UCP2 and UCP3 do not seem to contribute substantially to energy expenditure. Whether the induction of UCP1, the induction of other UCP or chemical mild uncoupling represent promising strategies for attenuating nutrient efficiency and counteracting obesity should be considered.
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PMID:Respiration uncoupling and metabolism in the control of energy expenditure. 1587 22

Leptin (LEP) and the uncoupling proteins 2 and 3 (UCP2/UCP3) are key molecules involved in the regulation of food intake and energy expenditure. However, their contribution to variation of obesity phenotypes in the general population remains controversial. The present study is to investigate whether chromosomal regions 7q and 11q, which contain LEP and UCP2/UCP3, respectively, can be excluded for linkage with obesity phenotypes. The obesity phenotypes include body mass index (BMI), fat mass, and percentage fat mass (PFM), with the latter two measured by dual-energy X-ray absorptiometry. We conducted exclusion linkage analyses using a variance component approach in a sample of 1816 individuals coming from 79 extended Caucasian pedigrees. In this study, we were able to exclude chromosomal region 7q containing LEP as having an effect on fat mass and PFM at effect sizes of 5% or greater, and on BMI at effect sizes of 10% or greater. We were able to exclude chromosomal region 11q containing UCP2/UCP3 as having an effect on fat mass and PFM at effect sizes of 10% or greater, and on BMI at effect sizes of 5% or greater. Our results suggest that the LEP and UCP2/UCP3 genes are unlikely to have a substantial effect on variation in obesity phenotypes in this particular US Caucasian population.
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PMID:Linkage exclusion analysis of two candidate regions on chromosomes 7 and 11: leptin and UCP2/UCP3 are not QTLs for obesity in US Caucasians. 1591 Jul 56

Loss of nonshivering thermogenesis in mice by inactivation of the mitochondrial uncoupling protein gene (Ucp1-/- mice) causes increased sensitivity to cold and unexpected resistance to diet-induced obesity at a young age. To clarify the role of UCP1 in body weight regulation throughout life and influence of UCP1 deficiency on longevity, we longitudinally analyzed the phenotypes of Ucp1-/- mice maintained in a room at 23 degrees C. There was no difference in body weight and lifespan between genotypes under the standard chow diet condition, whereas the mutant mice developed obesity with age under the high-fat (HF) diet condition. Compared with Ucp1+/+ mice, Ucp1-/- mice showed increased expression of genes related to thermogenesis and fatty acid metabolism, such as beta3-adrenergic receptor, in adipose tissues of the 3-month-old mutants; however, the augmented expression was reduced in Ucp1+/+ mice in 11-month-old Ucp1-/- mice fed the HF diet. Likewise, the increased levels of UCP3 and cAMP-dependent protein kinase in the brown adipose tissue of Ucp1-/- mice given the standard diet were decreased significantly in that of Ucp1-/- mice fed the HF diet, which animals showed impaired norepinephrine-induced lipolysis in their adipose tissues. These results suggest profound attenuation of beta-adrenergic responsiveness and fatty acid utilization in Ucp1-/- mice fed the HF diet, bringing them to late-onset obesity. Our findings provide evidence that UCP1 is neither essential for body weight regulation nor for longevity under conditions of standard diet and normal housing temperature, but deficiency increases susceptibility to obesity with age in combination with HF diet.
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PMID:UCP1 deficiency increases susceptibility to diet-induced obesity with age. 1592 71

Associations of obesity with its candidate genes, beta-adrenergic receptor genes (ADRBs), peroxisome proliferator-activated receptor-gamma (PPARgamma), and uncoupling proteins (UCPs) were studied in Korean adolescents. We analyzed the obesity-related phenotypes body mass index (BMI), percentage of body fat, plasma leptin and insulin levels, fasting glucose concentration, and plasma lipid profile in 329 teenagers to investigate the effects of seven single nucleotide variants 252G/A, 523C/A and 1053G/C in ADRB2; Trp64Arg in ADRB3; 161C/T in PPARgamma; Ala55Val in UCP2; and 210C/T in UCP3. The 1053G/C polymorphism (P < 0.05) in the ADRB2 gene and the Trp64Arg polymorphism (P < 0.01) in the ADRB3 gene were associated with BMI after adjustment for dietary energy intake. Trp64Arg polymorphism also influenced percentage of body fat (P < 0.01) and plasma leptin level (P < 0.05). Furthermore, significant interaction effects between the 1053G/C and Trp64Arg polymorphisms were observed on BMI (P < 0.01). The polymorphisms of the ADRB2 and ADRB3 genes explained 4.3% and 10.1% of the variation on BMI, and the two loci effect, including their epistasis, explained 18.3%. We concluded that 1053G/C and Trp64Arg polymorphisms of the ADRB genes additively and interactively contributed to the variation of complex adolescent obesity.
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PMID:Single nucleotide variants in the beta2-adrenergic and beta3-adrenergic receptor genes explained 18.3% of adolescent obesity variation. 1595 59

Accumulation of fat in the tissues results from the balance between energy intake and expenditure. The thyroid hormones have long been known to be the main regulators of basal metabolism through its stimulation of oxygen consumption in cells. The discovery of brown adipose tissue (BAT) and its unique activity of heat production and dissipation through the action of uncoupling protein-1 (UCP1) during cold stress, showed the relevance of this tissue for energy expenditure in lower mammals. UCP1 is only expressed in BAT through the synergistic action of norepinephrine (NE) and thyroid hormones in animals exposed to cold and to a lesser degree after meals. The uncoupling protein-2 (UCP2) is found in many tissues and exerts dual effects: it protects cells function from damage caused by reactive oxygen species (ROS). On the other hand, the uncoupling induced by UCP2 in mitochondria of pancreatic beta cells decreases ATP synthesis and impairs insulin secretion in response to glucose. Hyperlipidemia also prevents insulin secretion through a similar pathway, leading to hyperglycemia. The uncoupling protein-3 is found mostly in skeletal muscle and BAT and its absence did not alter heat production or body temperature. This protein would export fatty acids ouside the mitochondrial matrix for combustion in tissues where fat is the main fuel. In humans, the uncoupling proteins may not play a leading role in energy regulation. However, intensive studies on these and other factors influencing energy expenditure, appetite and glucose metabolism are taken place worldwide and may soon provide more clues on the mechanisms regulating energy balance and their use in the prevention or treatment of human obesity and diabetes type 2.
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PMID:[Role of uncoupling proteins UCP1, UCP2 and UCP3 in energy balance, type 2 diabetes and obesity. Synergism with the thyroid]. 1607 14

Evidence for the physiological functions of UCP2 and UCP3 is critically reviewed. They do not mediate adaptive thermogenesis, but they may be significantly thermogenic under specific pharmacological conditions. There is strong evidence that the mild regulated uncoupling they cause attenuates mitochondrial ROS production, protects against cellular damage, and diminishes insulin secretion. Evidence that they export fatty acids physiologically is weak. UCP2 and UCP3 are important potential targets for treatment of aging, degenerative diseases, diabetes, and perhaps obesity.
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PMID:Physiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3. 1609 26

To further explore the antiobesity effect of freeze-dried bitter melon (BM) juice, activities of mitochondrial lipid oxidative enzymes as well as the expression of uncoupling proteins and their transcription coactivator peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1alpha) were determined in diet-induced obese (DIO) rats. Rats were fed high-fat (HF) diets to induce obesity, and the effect of BM was assessed at doses of 0.75, 1.0, or 1.25% (wt:wt). In a dose-response experiment, BM-supplemented rats had lower energy efficiency (g weight gained/kJ consumed), visceral fat mass, serum glucose, and insulin resistance index, but higher plasma norepinephrine than unsupplemented rats (P < 0.05). Hepatic and skeletal muscle triglyceride concentrations were lower in supplemented HF diet-fed rats than in unsupplemented HF diet-fed rats (P < 0.05). An HF diet supplemented with BM elevated activities of hepatic and muscle mitochondrial carnitine palmitoyl transferase-I (CPT-I) and acyl-CoA dehydrogenase (AD) (P < 0.05). In another experiment, BM (1.0 g/100 g) lowered visceral fat mass but increased serum adiponectin concentration in HF diet-fed rats (P < 0.05). In the final study, rats were fed the HF diet with 0, 1.0 or 1.25% BM. Both groups of BM-supplemented rats had higher uncoupling protein 1 in brown adipose tissue (P < 0.05) and uncoupling protein 3 in red gastrocnemius muscle (P < 0.05), measured by Western blotting and RT-PCR, than the controls. The expression of the transcription coactivator PGC-1alpha in both tissues was also significantly elevated in the BM-supplemented rats (P < 0.05). The present results suggest that decreased adiposity in BM-supplemented rats may result from lower metabolic efficiency, a consequence of increased lipid oxidation and mitochondrial uncoupling.
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PMID:Reduced adiposity in bitter melon (Momordica charantia)-fed rats is associated with increased lipid oxidative enzyme activities and uncoupling protein expression. 1625 4

Mitochondrial uncoupling protein-1 (UCP1) has been thought to be a key molecule for thermogenesis during cold exposure and spontaneous hyperphagia and thereby in the autonomic regulation of energy expenditure and adiposity. However, UCP1 knockout (KO) mice were reported to be cold intolerant but unexpectedly did not get obese even after hyperphagia, implying that UCP1 may not be involved in the regulation of adiposity. Treatment of obese animals with beta3-adrenergic agonists is known to increase lipid mobilization, induce UCP1, and, finally, reduce body fat content. To obtain direct evidence for the role of UCP1 in the anti-obesity effect of beta3-adrenergic stimulation, in the present study, UCP1-KO and wild-type (WT) mice were fed on cafeteria diets for 8 wk and then given a beta3-adrenergic agonist, CL-316,243 (CL), or saline for 2 wk. A single injection of CL increased whole body oxygen consumption and brown fat temperature in WT mice but not in KO mice, and it elicited almost the same plasma free fatty acid response in WT and KO mice. WT and KO mice increased similarly their body and white fat pad weights on cafeteria diets compared with those on laboratory chow. Daily treatment with CL resulted in a marked reduction of white fat pad weight and the size of adipocytes in WT mice, but not in KO mice. Compared with WT mice, KO mice expressed increased levels of UCP2 in brown fat but decreased levels in white fat and comparable levels of UCP3. It was concluded that the anti-obesity effect of beta3-adrenergic stimulation is largely attributable to UCP1, but less to UCP2 and UCP3, and thereby to UCP1-dependent degradation of fatty acids released from white adipose tissue.
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PMID:Indispensable role of mitochondrial UCP1 for antiobesity effect of beta3-adrenergic stimulation. 1636 88


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