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

Obesity is a chronic metabolic disorder associated with CVD and increased morbidity and mortality. When the BMI is > or = 30 kg/m2, mortality rates from all causes, and especially CVD, are increased by 50% to 100%. There is strong evidence that weight loss in overweight and obese individuals improves risk factors for diabetes and CVD. Additional evidence indicates that weight loss and the associated diuresis reduce blood pressure in both overweight hypertensive and nonhypertensive individuals, reduce serum TG levels, increase high-density lipoprotein cholesterol levels, and may produce some reduction in low-density lipoprotein cholesterol concentrations. Of interest, even if weight loss is minimal, obese individuals showing a good level of cardiorespiratory fitness are at reduced risk for cardiovascular mortality than lean but poorly fit subjects. Insulin and catecholamines have pronounced metabolic effects on human adipose tissue metabolism. Insulin stimulates LPL and inhibits HSL; the opposite is true for catecholamines. There is regional variation in adipocyte TG turnover favoring lipid mobilization in the visceral fat depots and lipid storage in the peripheral subcutaneous sites. The hormonal regulation of adipocyte TG turnover is altered in obesity and is most marked in central obesity. There is resistance to insulin stimulation of LPL; however, LPL activity in fasted obese subjects is increased and remains so following weight reduction. Catecholamine-induced lipolysis is enhanced in visceral fat but decreased in subcutaneous fat. Numerous adaptive responses take place with physical training. These adaptations result in a more efficient system for oxygen transfer to muscle, which is now able to better utilize the unlimited lipid stores instead of the limited carbohydrate reserves available. In addition, the reduced adipose tissue mass represents an important mechanical advantage, allowing better long-term work. Gender differences have been reported in the adaptation of adipose tissue metabolism to aerobic exercise training. Physical training helps counteract the permissive and affluent environment that predisposes reduced-obese subjects to regain weight. An exercise program using weight resistance modalities may also be included safely, and it improved program retention in a multidisciplinary weight management program that was designed for obese children. Thirty to 45 minutes of physical activity of moderate intensity, performed 3 to 5 days a week, should be encouraged. All adults should set a long-term goal to accumulate at least 30 minutes or more of moderate-intensity physical activity on most, and preferably all days. Public health interventions promoting walking are likely to be the most successful. Indeed, walking is unique because of its safety, accessibility, and popularity. It is noteworthy that there is a clear dissociation between the adaptation of cardiorespiratory fitness and the improvements in the metabolic risk profile that can be induced by endurance training programs. It appears that as long as the increase in energy expenditure is sufficient, low-intensity endurance exercise is likely to generate beneficial metabolic effects that would be essentially similar to those produced by high-intensity exercise. The clinician should therefore focus on the improvement of the metabolic profile rather than on weight loss alone. Realistic goals should be set between the clinician and the patient, with a weight loss of approximately of 0.5 to 1 pound per week. It should be kept in mind that since it generally takes years to become overweight or obese, a weight loss pattern of 0.5 or 1 pound per week will require time and perseverance to reach the proposed target. However, the use of physical activity as a method to lose weight seems inversely related to patients' age and BMI and directly related to the level of education. Thus, public health interventions helping these groups to become physically active remain a challenge and further emphasize the importance of the one-on-one interaction between the clinician/health care professional with the obese individual "at risk" of CVD. This notion is critical, as it has been shown that less than half of obese adults have reported being advised to lose weight under the guidance of health care professionals.
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PMID:Exercise in weight management of obesity. 1157 Jan 17

Hereditary factors may be involved in the pathogenesis of type 2 diabetes. A polymorphism in the hormone-sensitive lipase (HSL) gene (HSLi6) is associated with obesity and diabetes, although it is unknown whether the polymorphism is functional and thereby influences lipolysis. We genotyped 355 apparently healthy nonobese male and female subjects for the HSLi6 polymorphism. Allele 5 was found to be the most common allele (allele frequency 0.57). In 117 of the subjects, we measured abdominal subcutaneous fat cell lipolysis induced by drugs acting at various steps in the lipolytic cascade. The lipolysis rate induced by norepinephrine isoprenaline (acting on beta-adrenoceptors), forskolin (acting on adenylyl cyclase), and dibutyryl cyclic AMP (acting on HSL) were all decreased by approximately 50% in allele 5 homozygotes, as compared with noncarriers. Heterozygotes showed an intermediate lipolytic rate. The difference in lipolysis rate between genotypes was more pronounced in men than in women. We conclude that allele 5 of the HSLi6 polymorphism is associated with a marked decrease in the lipolytic rate of abdominal fat cells. This may in turn contribute to the development of obesity.
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PMID:A common hormone-sensitive lipase i6 gene polymorphism is associated with decreased human adipocyte lipolytic function. 1157 28

Cytokines appear to be major regulators of adipose tissue metabolism. Therapeutic modulation of cytokine systems offers the possibility of major changes in adipose tissue behaviour. Cytokines within adipose tissue originate from adipocyte, preadipocyte and other cell types. mRNA expression studies show that adipocytes can synthesise both tumour necrosis factor alpha (TNF-alpha) and several interleukins (IL), notably IL-1beta and IL-6. Other adipocyte products with 'immunological' actions include complement system products and macrophage colony-stimulating factor. Cytokine secretion within adipocytes appears similar to that of other cells. There is general agreement that circulating TNF-alpha and IL-6 concentrations are mildly elevated in obesity. Most studies suggest increased TNF-alpha mRNA expression or secretion in vitro in adipose tissue from obese subjects. The factors regulating cytokine release within adipose tissue appear to include usual 'inflammatory' stimuli such as lipopolysaccaride, but also the size of the fat cells per se and catecholamines. There is conflicting data about whether insulin and cortisol regulate TNF-alpha. The effects of cytokines within adipose tissue include some actions that might be characterised as metabolic. TNF-alpha and IL-6 inhibit lipoprotein lipase, and TNF-alpha additionally stimulates hormone-sensitive lipase and induces uncoupling protein expression. TNF-alpha also down regulates insulin-stimulated glucose uptake via effects on glucose transporter 4, insulin receptor autophosphorylation and insulin receptor substrate-1. All these effects will tend to reduce lipid accumulation within adipose tissue. Other effects appear more 'trophic', and include the induction of apoptosis, regulation of cell size and induction of de-differentiation (the latter involving reduced peroxisome proliferator-activated receptor gamma). Cytokines are important stimulators and repressors of other cytokines. In addition, cytokines appear to modulate other regulatory systems. Examples of the latter include effects on leptin secretion (probably stimulation followed by inhibition) and reduction of beta3-adrenoceptor expression. There seems to be no clear agreement as to which cytokines derived from adipose tissue act as remote regulators, i.e. hormones. Leptin, which is structurally a cytokine, is also a hormone. IL-6 appears to be released systemically by adipose tissue, but TNF-alpha is probably not. Both leptin and IL-6 appear to act on the hypothalamus, IL-6 acts on the liver, while leptin may have actions on the pancreas. The importance of the immune system in whole-body energy balance provides a rationale for the links between cytokines and adipose tissue. It seems clear that TNF-alpha is a powerful autocrine and paracrine regulator of adipose tissue. Other cytokines, notably leptin, and possibly IL-6, have lesser actions on adipose tissue. These cytokines act as hormones, reporting the state of adipose tissue stores throughout the body.
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PMID:Pro-inflammatory cytokines and adipose tissue. 1168 9

Free fatty acids released during triglyceride lipolysis play an important role in obesity-associated insulin resistance of glucose disposal. Individual sensitivity of lipolysis to the suppressive effect of insulin varies greatly among healthy subjects. It is possible that genetic factors contribute to this variation. Among the many proteins involved in the regulation of lipolysis, hormone-sensitive lipase (HSL) represents a prime candidate for genetic variants contributing to the biological variation of insulin sensitivity of lipolysis. We determined the insulin sensitivity of lipolysis (suppression of isotopically [primed-continuous infusion of d5 glycerol] measured glycerol rate of appearance) and of glucose disposal, using a three-step (n = 20) or standard (n = 53) hyperinsulinemic euglycemic clamp in 73 healthy, unrelated subjects. To assess the possible role of genetic polymorphisms, we directly sequenced the coding region of the HSL gene and the noncoding exon B from these subjects. We identified two silent mutations and three amino acid polymorphisms: Arg262Met (prevalence, 5%), Glu620Asp (prevalence, 31%) and Ser681Ile (prevalence, 22%). The latter two are located in the regulatory domain of HSL but neither had a significant impact on insulin sensitivity of lipolysis or glucose disposal (with and without adjustment for obesity and age as covariates; all P values > 0.20). We conclude that a number of genetic polymorphisms in HSL exist, some of which are highly prevalent. Neither of the polymorphisms we identified in the coding region, however, contributed measurably to the biological variation of insulin sensitivity in our lean, healthy population.
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PMID:Two novel prevalent polymorphisms in the hormone-sensitive lipase gene have no effect on insulin sensitivity of lipolysis and glucose disposal. 1238 May 67

Catecholamines are the major lipolytic hormones in human fat cells, and lipolytic catecholamine resistance is described in obesity. Studies on twins and in rare genetic disorders suggest a strong heredity component of catecholamine-induced lipolysis. Polymorphisms in catecholamine receptor signalling pathways have been described, several of which associate with obesity. Many polymorphisms in adrenoceptor genes are functional in transfected cell lines. The importance of polymorphisms in catecholamine signalling pathways for lipolysis regulation is discussed. A Trp64Arg polymorphism in the beta3-receptor, which associates with obesity, is accompanied by changes in lipolytic sensitivity of the receptor in human fat cells. Similarly, a Gln16Glu and an Arg164Ile variation in the beta2-adrenoceptor cause marked variations in the lipolytic sensitivity of this receptor in human adipocytes. Furthermore, beta2-adrenoceptor gene polymorphisms associate with obesity. A dinucleotide (CA) intron repeat in hormone-sensitive lipase gene is linked to obesity and markedly decreases the ability of catecholamines to activate the lipase and thereby lipolysis in human fat cells. However, an Arg389Gly polymorphism in the beta1-adrenoceptor, which alters receptor function in transfected cell lines, has no effect on lipolysis in human fat cells and is not associated with obesity. Thus, polymorphism in human genes that are involved in catecholamine signal transduction have effects on fat cell lipolysis and also relate to obesity. The lipolysis effects of these polymorphisms cannot always be predicted from gene transfer experiments on artificial cell lines. It is possible that genetic variance in catecholamine signalling pathways, through alterations in adipocyte lipolysis, may promote obesity.
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PMID:Genetic variance and lipolysis regulation: implications for obesity. 1173 Jan 61

The influence of obesity on the lipolytic capacity of isolated sc fat cells was studied prospectively in 13 women and 10 men, all obese, but otherwise healthy, before and 2 and 3 yr after weight reduction by bariatric surgery. Nonobese subjects (25 women and 17 men) without a family history of obesity served as the control group. Lipolytic capacity was determined after stimulation at different steps of the lipolytic cascade with noradrenaline, isoprenaline, forskolin, and (Bu)(2)AMP. Bariatric surgery was followed by a marked and similar reduction of body mass index and fat cell volume (approximately 40%) in both genders. Before weight loss, lipolytic capacity per cell was elevated in obese women and decreased to normal levels after weight reduction at 2 and 3 yr. However, lipolytic capacity per fat cell surface area was not changed in obese women. In obese men, lipolytic capacity per cell was almost the same as in lean men and was not influenced by weight reduction. Lipolytic capacity was related to fat cell size in women (P = 0.0008; r = 0.58), but not in men (P = 0.67; r = 0.086). The protein content of hormone-sensitive lipase, which determines lipolytic capacity, was significantly lower in obese men and women and increased slightly after weight reduction in men only. Thus, in women, but not in men, the adipocyte lipolytic capacity is influenced by obesity and weight reduction, probably due to changes in fat cell size. These gender differences are not related to the amount of hormone-sensitive lipase protein in adipocytes.
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PMID:Major gender differences in the lipolytic capacity of abdominal subcutaneous fat cells in obesity observed before and after long-term weight reduction. 1183 18

Salacia (S.) reticulata, a Hippocrateaceae plant distributed in Sri Lankan and Indian forests, has been used as a supplementary food in Japan to prevent obesity and diabetes. We examined the antiobesity effects of the hot water-soluble extract (SRHW) from the roots of S. reticulata using obese rat models and an in vitro study. Body weight (P = 0.07) and periuterine fat storage (P = 0.10) in female Zucker fatty rats (8-9 wk old) tended to be suppressed by oral administration of SRHW (125 mg/kg) for 27 d. Male rats fed a high fat diet were not affected by SRHW. Furthermore, SRHW inhibited porcine pancreatic lipase (PL), rat adipose tissue-derived lipoprotein lipase (LPL) and glycerophosphate dehydrogenase (GPDH) activities with 50% inhibitory concentrations (IC(50)) of 264 (95% confidence limits: 203-393) mg/L, 15 (12-18) mg/L and 54 (35-85) mg/L, respectively, but did not inhibit hormone-sensitive lipase activity in rat adipose tissue. Next, we examined the effects of polyphenols, di- and triterpenes and salacinol isolated from the roots of S. reticulata on lipid metabolizing enzymes and lipolysis. (-)-Epigallocatechin and (-)-epicatechin-(4beta-->8)-(-)-4'-O-methylepigallocatechin inhibited PL activity with IC(50) of 88 (not calculated) and 68 (26-122) mg/L, respectively. (-)-Epicatechin, 3beta, 22beta-dihydroxyolean-12-en-29-oic acid and the tannin fraction inhibited LPL activity with IC(50) of 81 (54-214), 89 (62-214) and 35 (24-62) mg/L. Only the tannin fraction inhibited GPDH activity with an IC(50) of 6.8 (3.4-10.9) mg/L. These constituents may be involved in the lipase and GPDH inhibitory activities of SRHW. On the other hand, SRHW at 100 mg/L tended to enhance lipolysis in rat adipocytes (P = 0.06). Significant lipolytic effects were exerted by mangiferin, (-)-4'-O-methylepigallocatechin and maytenfolic acid at 100 mg/L (P < 0.01). In conclusion, polyphenolic compounds may be involved in the antiobesity effects of SRHW in rats through inhibition of fat metabolizing enzymes (PL, LPL and GPDH) and enhanced lipolysis.
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PMID:Salacia reticulata and its polyphenolic constituents with lipase inhibitory and lipolytic activities have mild antiobesity effects in rats. 1209 53

Insulin resistance, obesity, and diabetes are characterized by hyperglycemia, hyperinsulinemia, and hyperleptinemia and are associated with increased risk of atherosclerosis. In an effort to understand how this occurs, we have investigated whether these factors cause disregulation of cholesterol ester metabolism in J774.2 macrophages. Raising glucose levels alone was sufficient to increase uptake of acetylated low density lipoprotein but did not stimulate synthesis of cholesterol esters. In the presence of high glucose, both insulin and leptin increased the rate of cholesterol ester synthesis, although they did not further increase uptake of acetylated low density lipoprotein. However, in the presence of high glucose both insulin and leptin caused a significant increase in the activity of acyl-CoA: cholesterol O-acyltransferase (ACAT) combined with a significant reduction in the level of hormone-sensitive lipase (HSL). Because ACAT is the main enzyme responsible for cholesterol ester synthesis and HSL contributes significantly to neutral cholesterol ester hydrolase activity, this suggests that glucose primes the J774.2 cells so that in the presence of high insulin or leptin they will store cholesterol esters. This contrasts with 3T3-L1 adipocytes, where HSL activity and expression are increased by insulin in high glucose conditions. These findings may provide an explanation for the observation that in conditions characterized by hyperglycemia, hyperleptinemia, and hyperinsulinemia, triglyceride lipolysis in adipocytes is increased while hydrolysis of cholesterol esters in macrophages is decreased, contributing to foam cell formation.
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PMID:Glucose-dependent regulation of cholesterol ester metabolism in macrophages by insulin and leptin. 1220 Apr 16

To clarify the role of the neuropeptide Y (NPY) Y5 receptor subtype in energy homeostasis, the effect of the intracerebroventricular infusion of a selective Y5 agonist, D-Trp(34)NPY, was investigated in C57BL/6J mice. Intracerebroventricular infusion of D-Trp(34)NPY (5 and 10 microg/d) produced hyperphagia and body weight gain, accompanied by increased adipose tissue weight, hypercholesterolemia, hyperinsulinemia, and hyperleptinemia. Oral administration of a selective Y5 antagonist at a dose of 100 mg/kg twice a day completely suppressed all of these D-Trp(34)NPY-induced changes, indicating that chronic activation of the Y5 receptor produces hyperphagia and obesity. In addition, D-Trp(34)NPY still resulted in an increase in adipose tissue weight accompanied by hyperleptinemia and hypercholesterolemia, although D-Trp(34)NPY-induced food intake was restricted by pair-feeding. Under the pair-fed condition, D-Trp(34)NPY decreased hormone-sensitive lipase activity in white adipose tissue and uncoupling protein-1 mRNA expression in brown adipose tissue. These findings indicate that Y5-mediated obesity may involve metabolic changes, such as decreased lipolysis and thermogenesis, as well as hyperphagia. Therefore, the Y5 receptor can play a key role in regulating energy homeostasis.
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PMID:Characterization of neuropeptide Y (NPY) Y5 receptor-mediated obesity in mice: chronic intracerebroventricular infusion of D-Trp(34)NPY. 1269 85

Lipolytic catecholamine resistance in sc fat cells is observed in polycystic ovarian syndrome (PCOS). The mechanisms behind this lipolysis defect were explored in vitro; sc fat cells were obtained from 10 young, nonobese PCOS women and from 14 matched, healthy control women. Fasting plasma glycerol levels were reduced by one third in PCOS (P < 0.05). Adipocytes of PCOS women were about 25% larger than in the controls (P < 0.05) and had 40% reduced noradrenaline-induced lipolysis (P < 0.05), which could be attributed to a 10-fold decreased beta(2)-adrenoceptor sensitivity (P < 0.05) and low ability of cAMP to activate the protein kinase A (PKA)/hormone-sensitive lipase (HSL) complex (P < 0.05). In PCOS, the adipocyte protein content of beta(2)-adrenoceptors, HSL, and the regulatory II beta-component of PKA were 70%, 55%, and 25% decreased, respectively (P < 0.001); but there was no change in the amount of the catalytic subunit of PKA or of beta(1)-adrenoceptors. Thus, lipolytic catecholamine resistance of sc adipocytes in PCOS is probably attributable to a combination of decreased amounts of beta(2)-adrenergic receptors, the regulatory II beta-component of PKA, and HSL. This may cause low in vivo lipolytic activity and enlarged sc fat cell size and promote later development of obesity in PCOS.
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PMID:Mechanisms behind lipolytic catecholamine resistance of subcutaneous fat cells in the polycystic ovarian syndrome. 1272 85


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