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Adipose Tissue and Atherosclerosis: Exploring the Connection

Giamila Fantuzzi and Theodore Mazzone
Arterioscler Thromb Vasc Biol 2007;27;996-1003; originally published online Feb 15,
DOI: 10.1161/ATVBAHA.106.131755
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Diabetes & Metabolism. large vessel atherosclerosis.1% of US children were obese (as defined white individuals who had quantitation of coronary artery by being greater than the 95th percentile of sex-specific calcium an average of 8 years apart. as opposed to peripheral. MD. especially among the young. The unfolding role of adipose tissue as an important metabolic and secretory organ provides new opportunities for developing more effective approaches for preventing obesity and its atherosclerotic complications. In tissue on direct measures of macrovascular disease. factors secreted by adipose tissue may directly influence vessel wall homeostasis by influencing the function of endothelial cells.F. arterial smooth muscle cells. Numerous studies have shown the beneficial effects of weight loss on markers of cardiovascular risk but fewer have demonstrated improvement in direct measures of large vessel disease. This review focuses on the contribution of predictor of coronary artery calcium.11 BMI was associated with both fatty streaks wall. Original received September 11. Studies predicted coronary artery calcium. In addition. Approxi.ahajournals.9% of women in the undergoing a single measurement of coronary artery calcium. and Pharmacology (T. lipid/lipoprotein metabolism. Obesity is associated with accelerated atherosclerosis and increased rates of cardiovascular death. is available at http://www. 1819 W Polk St (M/C 797). Brief Reviews Adipose Tissue and Atherosclerosis Exploring the Connection Giamila © 2007 American Heart Association. Cassidy et al studied 443 asymptomatic 2003 to 2004.27:996-1003. the pattern of gene expression and secretory products in visceral fat would be predicted to be more atherogenic compared with that in subcutaneous peripheral fat. visceral fat measured by CT scan cardiovascular death. 2007. is dramatically increasing in the United States. and systemic inflammation.M. the Pathobiological De- vessel atherosclerosis in humans are considered.).1–3 Of special concern is the sharp increase in obesity among children and adolescents. and macrophages in the vessel wall. final version accepted February 2. linear regression models adjusting for the baseline risk factors. 17. 2010 . several indices of obesity predicted the progression of coronary mately 32. Chicago.4 –7 A number of more recent vessel wall and for evaluating how adipose tissue distribution or studies have specifically reported on the effect of excess adipose reduction (weight loss) impact atherosclerosis. Medicine (T.1161/ATVBAHA. risk factors showed that waist-to-hip ratio was a significant vascular death. Section of Endocrinology. University of Illinois at Chicago.8 After fitting multivariable body mass index (BMI) for age growth charts). and raised lesions in the right coronary artery and stenosis in the left anterior descending artery. expands the opportunities for investigating potential mecha- pose tissue for increasing cardiovascular death for adolescents nisms by which excess adipose tissue adversely impacts the and adults up to 75 years of age. (Arterioscler Thromb Vasc by on March 17. E-mail tmazzone@uic.10 With respect to obesity and measuring the effect of obesity on direct measures of large atherosclerosis in younger individuals.) Key Words: obesity 䡲 atherosclerosis 䡲 adipocytokines 䡲 lipoprotein metabolism 䡲 visceral fat T he prevalence of obesity is dramatically increasing in the United States. aged 15 to 34 years. dying of excess adipose tissue could adversely affect the vessel external causes.9 In another multiethnic excess adipose tissue to the major underlying cause of study in type 2 diabetes. a United States.). There is general agreement that central. University of Illinois at Chicago. From the Departments of Human Nutrition (G. adipose tissue confers the most cardio-metabolic risk.2% of US adults are obese as defined by a arthrosclerosis in a group otherwise defined as low risk for BMIⱖ30 kg/m2. There are many plausible mechanisms by which an increase in adipose tissue could adversely affect the vessel wall. along terminants of Atherosclerosis in Youths Study collected arteries with evidence regarding potential mechanisms by which and tissue from 3000 persons.8% of men and 6. cantly increased compared with 1999 to 2000. Correspondence to Theodore Mazzone. Using the measurement of coronary artery calcium as a marker for coro- nary atherosclerosis. including cardio.). glucose level. Many studies have demonstrated that obe.atvbaha. Extreme obesity (defined as a BMIⱖ40 cardiovascular disease. Theodore Mazzone Abstract—The prevalence of obesity. 2006. Numerous studies have demonstrated the effect of excess adi. Inc. Arterioscler Thromb Vasc Biol. T.M.131755 996 Downloaded from atvb. 2007.M. signifi. multivariate analysis that corrected for multiple cardiovascular sity increases mortality from all causes. In a study of 495 diabetic subjects kg/m2) affects 2. Although the basis of this differential risk has not been not established.. demonstrated by imaging approaches. The link between obesity and Obesity and Atherosclerosis macrovascular DOI: 10. These include the changes in blood pressure. IL 60612.

in a study Mechanisms of Injury of white men with BMI values ranging from 22 to 35 kg/m2. these same tein metabolism.ahajournals. apolipoprotein B (apoB). the production of metabolites. Adipose tissue– derived factors also can directly regulate gene expression and function of endothelial.14 Metabolites. as does treatment with creased release of fatty acids from adipose tissue in obesity peroxisome proliferator-activated receptor-␥ agonists. very-low-density lipoprotein apoB concentration. Obesity has a number of conse. and apoE secreted by extra- with its favored access to the portal circulation. and weight loss produces significant influence systemic lipid and lipoprotein metabolism.22. ApoE is highly expressed in adi- cytokines. and hormones released by adipose tissue can target pose tissue and its expression increased by treatment with the liver. and macrophage cells in the vessel wall.15. 12. Visceral adipose tissue. There are numerous mechanisms by which obesity can adiponectin was the most significant predictor of plasma adversely affect the vasculature and thereby increase cardio. tumor necrosis factor. components for defending vessel wall homeostasis. including hy. including adipocytes. arterial adipocyte triglyceride turnover and adipocytokine expres- smooth muscle cells.15–18 Other factors secreted by adipose tissue may cause number of important effects on the metabolism and function Downloaded from atvb. decreases in serum amyloid A by on March 17. Fantuzzi and Mazzone Adipose Tissue and Atherosclerosis 997 Adipose tissue products work directly at the vessel wall and through the liver to modulate the atherogenic environment of the vessel wall. These sion. and hormones by adipose tissue is altered.14 Its level of expression is highly There are multiple mechanisms by which obesity can correlated with BMI.23 clotting factors and inflammatory factors impact the athero.26 In with increased flux to the liver can increase very-low-density inflammatory conditions. 2010 .24 Endogenous expression of apoE in adipo- adipose tissue– derived factors have been shown to influence cytes has also been shown to play an important role in gene expression and cell function in endothelial cells. cellular lipoprotein metabolism. important surface constituent of HDL and thereby has a tion. plasminogen activator inhibitor. through changes in liver-derived lipoproteins. obese subjects and could have multiple effects on lipid pertension.21 Adipose tissue can also tissue have been considered as important mechanisms for the influence systemic lipoprotein metabolism and function by adverse effects of adiposity on the vessel wall. peroxisome proliferator-activated receptor-␥ agonists. At the liver. secreting apolipoproteins. In the case of visceral adipose tissue. and monocytes/macrophages.25 Serum amyloid A is both an inflammatory cytokine represent the major cell types of the artery wall and are key and an apolipoprotein produced by multiple cell types. diabetes. could be hepatic tissue can have a profound effect on systemic lipopro- especially important in this pathway. Excess Adipose Tissue and the Vessel Wall: adverse effects on circulating lipids. cytokines. In obesity.20. and dyslipidemia. In addition.19 Tumor vascular mortality (Figure). arterial smooth muscle. For example. and triglyceride secre. TNF.15 In. PAI. FFA indicates free fatty acids. serum amyloid A becomes an lipoprotein. ApoE is a key apolipoprotein involved in the systemic and genic environment of the vessel wall. necrosis factor expression is increased in adipose tissue from quences known to accelerate atherosclerosis. and.13 Systemic metabolism via both paracrine effects on adipocytes. as well inflammation and the production of adipokines by adipose as on effects in the liver. adipose tissue– derived factors influence the composition and level of circulating lipoproteins and the levels of systemic inflammatory and clotting system components. these factors will have favored access to the liver through the portal circulation.

recombinant leptin has been to date. 2010 . and poten- dently predicted all-cause and cardiovascular mortality after tiates proliferation. artery disease.70 Treatment of apoE-deficient mice with an adi- Downloaded from atvb. and this association was independent of insulin of the adiponectin knockout strains that have been developed resistance. these alterations have not been observed in all calcium. C-reactive protein (CRP).27–29 Two other apolipoproteins are also produced in shown to promote atherosclerosis and thrombosis in apoE- adipocytes.998 Arterioscler Thromb Vasc Biol. and ␤-blocker. recent data from Kunnari et al different oligomers. an effect that is antago. BMI. thereby promoting formation of foam cells. and several increasing coronary atherosclerosis measured by coronary recent publications have suggested a role for adiponectin in artery calcium after adjustment for established cardiac risk modulating vessel wall health.30 Excess free fatty acid tion of and cytokine production by macrophages.50 This adverse effect on vascular disease was lipoprotein metabolism or cellular lipid flux is less well observed in spite of the metabolic benefits associated with defined. Resistin directly activates the endothelium through model assessment of insulin resistance. resistin type 1 diabetes and nondiabetic subjects aged 19 to 59 increases expression of CD36 and facilitates lipid accumula. In endothelial cells.42 On the other hand.14 Levels its expression is increased by treatment with endotoxin and of adiponectin increase with weight loss or with pharmaco- proinflammatory cytokines. a high-fat and mans.62 has been shown to extend to the peripheral effects of but not all.ahajournals. probably mediated by alterations in tissue may also influence vessel wall directly.62. logical treatment of insulin resistance.49 In animal models. and pentraxin by Rewers and colleagues studied the progression of coronary endothelial cells. the level of resis.37. studies have shown that resistin levels are also leptin. apoC1 and apoD.56 Leptin also contributes to increased activa- creatinine.64. cose tolerance. HDL. resistin nondiabetic subjects. neutrophils. statin use.64.44. leptin treatment. tin levels correlate negatively with triglyceride.15 but their impact on systemic deficient mice.69.14. where humans is decreased in obese and diabetic subjects.67 Adiponectin levels were inversely correlated to tion. as measured by coronary artery aorta. leptin pro- adjustment for age. Leptin resistance. including those on platelets and the vascular wall. Adiponectin plays a tin in humans has been shown to positively correlate with role in regulating systemic substrate metabolism. sex.61 Although these effects of fatty acids have also been shown to induce endothelial cell leptin point to a proatherogenic role for this adipokine.6 years in a group of patients with vascular smooth muscle cells.36 Some. this effect is progression of coronary artery calcium in both diabetic and also antagonized by adiponectin.43 High levels of resistin may negatively total serum adiponectin and high-molecular-weight adiponec- influence the atherosclerotic process through several mecha.66 independent of other cardiac risk factors. homocysteine. and this effect has been observed independent of BMI high-sucrose diet leads to marked elevation of plasma glucose and traditional cardiac risk factors.45 It also promotes migratory activity of artery calcification over 2. Free fatty acid levels in these subjects indepen. Other studies have shown that leptin may Increased free fatty acid release from adipose tissue in have a role in neointimal formation in response to arterial obesity may also accelerate atherosclerosis by mechanisms injury.45 Resistin also induces ponectin level is significantly lower in men with coronary production of the proinflammatory cytokines endothelin-1.32 Free increasing platelet aggregation. insulin resistance. LDL.65 HDL cholesterol and high-molecular- marker of atherosclerosis/cardiovascular risk. homeostasis nisms. Resistin is leptin receptor signaling pathways and originally reported in highly expressed in the fat tissue of rodents. diabetes mellitus.48 in a group of subjects with type 2 diabetes. and both media thickness. Evidence for this is provided by wall. Adiponectin levels after treatment with induces production of the proinflammatory cytokines tumor insulin sensitizers have also been shown to be the best necrosis factor-␣ and interleukin (IL)-12 by macrophages predictor of an improvement in carotid arterial wall stiffness through activation of nuclear factor ␬B.39 – 41 Recently. proliferation and hypertrophy. and circulating in- upregulation of adhesion molecules. and its level is the hypothalamus of obese subjects and experimental ani- elevated in models of obesity and insulin resistance. it is apoptosis and to impair endothelium-dependent important to note that obesity is associated with leptin vasodilatation.68 In adiponectin knockout mice. delivery to peripheral tissues may worsen insulin resistance and T lymphocytes. smoking.47 Furthermore.33–35 resistance. which leads to a reduced biological response to A number of cytokines and adipokines secreted by adipose by on March 17.65 Serum high-molecular-weight adi- nized by adiponectin (see below). flammatory markers. many of which are similar to those described for the results of a prospective study of 3315 subjects followed resistin. May 2007 of HDL. and plasma leptin levels adiponectin gene are strongly associated with impaired glu- increase with obesity. Plasma leptin levels have been posi. motes migration.57–59 Finally. and an increase in diabetes demonstrated that hyperleptinemia was associated intimal smooth muscle cell proliferation after injury in the with coronary atherosclerosis.31. years. and its level in resistin is expressed primarily in inflammatory cells. and coronary artery disease tively associated with cardiovascular complications in hu. and each of these may has a different showed no relationship between resistin levels and another biologic function. protein kinase.52–55 In smooth muscle cells.63 increased in human obesity and diabetes. increases production of MCP-1 and endothelin-1. of cells of the vascular wall60 and facilitates thrombosis by possibly through activation of Toll-like receptor 4. Adiponectin circulates in 3 factors.14 A recent study in type 2 and insulin levels. leptin induces oxidative stress. in humans. Adiponectin is a product of adipocytes. triglycerides.3 years. this latter homeostasis model assessment of insulin resistance.38 In humans. for 5. leptin promotes calcification and may play a role in activating inflammatory processes.68 Mutations of the Leptin is a product of adipocytes. however. effect being mediated by activation of p38 mitogen-activated tension.44.51 Leptin has multiple effects on cells of the artery not directly related to lipids. monocyte chemoattractant protein (MCP)-1.41 In macrophages. carotid intima/ weight adiponectin level are positively correlated. hyper. mals.

No relationship was obese women (aged 34 to 62 years) during a 14-week weight found between coronary artery disease and BMI. Thigh girth correlated positively with HDL and disease was significantly correlated with visceral adipose with LDL particle size in women.76. Fantuzzi and Mazzone Adipose Tissue and Atherosclerosis 999 ponectin adenovirus has been shown to reduce plaque forma. number of studies have shown that a reduction in visceral fat and inhibiting. tumor necrosis factor-␣. and blood pressure.14 ated with stiffness of the carotid and femoral arteries. tectomy. followup.14 Angiotensin II produces vasoconstrictive effects and among truncal fat. or adiponectin.14 Plasminogen stiffness of large arteries. with a BMI⬎35 kg/m2 to adjustable gastric banding alone.75 In vascular smooth muscle cells. The comparison thereby reverses the effects of resistin. both sensitivity.78 Similar to what this plus surgical removal of the greater omentum. patterns of gene expression be- with improvement in CHD risk factors.95 and ides and small dense LDL particles and negatively with HDL multivariate regression analyses showed that coronary artery cholesterol. 2010 .72–73 However. and up to one-third of plasma IL-6 is believed groups. controversy remains regard. or change the plasma concentrations of CRP. and estimates of the may also promote systemic inflammation. and insulin levels independent of the change in BMI. subcutaneous abdominal tissue by 44% in subjects with atherogenic and antiinflammatory program of gene expres. and those with type through inhibition of nuclear factor ␬B activation71 and 2 diabetes lost 10 kg of fat (19% of total fat). such as heparin. eters in 15 obese women before. normal glucose tolerance. On the other hand. Adiponectin downregu. In a study of more Adipose Tissue Distribution than 5000 middle-aged women aged 30 to 69 years. In humans. IL-6 produces Several recent studies have reported on the influence of elevation of plasma free fatty acids and increased levels of adipose tissue distribution on direct measures of macrovas- hepatic CRP expression. tion in the aortic sinus by 30%. studied 55 patients undergoing coronary angiography. bolic parameters were compared before surgery and 2 years ing the role of adiponectin for macrophage cytokine after surgery. whereas fat tissue change in the trunk correlated under active investigation. including MCP-1. who were apparently healthy and examined the relationship ty.ahajournals.74. but the difference was creased circulating MCP-1 levels have been shown to not statistically significant. Terry et al85 reported that waist-to-hip ratio) women to lean women. peripheral fat. whereas peripheral fat was inversely associated with stiffness of the Differences in Atherosclerotic Risk Based on brachial and carotido-femoral segment. adiponectin promotes an anti.88 Meta- was reported in endothelial cells.87 Liposuction reduced the volume of on the above observations. Ferreira et al investigated 336 subjects (175 women) tissue.94 Morricone et al waist-to-thigh girth ratio positively correlated with triglycer. lost more weight than control subjects. adiponectin reduces lipid accumulation and down.77 In macro. where their level of expression is increased in obesi. Klein et al examined tween peripheral subcutaneous and visceral fat are consistent the effect of removing subcutaneous fat on metabolic param. and plas. media thickness was observed in abdominally obese (elevated that present in the hips and thighs). angiotensin-converting enzyme. Peripheral fat mass showed an Angiotensinogen. there was a decrease in weight and improved matory mediators in adipose tissue. produce significant changes in blood pressure. or regulates expression of scavenger receptors. however. induction and suppression of chemokine production by endo. insulin.14 Vohl et Downloaded from atvb. Omentectomized subjects pocyte expression of MCP-1 increases in obesity. Subjects who underwent omen- increase the number of circulating CD11B-positive mono.45 Adiponectin also of pre-liposuction and post-liposuction values showed that reduces endothelial oxidative stress and proliferation while removal of subcutaneous fat did not significantly alter insulin stimulating nitric oxide synthase activity. There were no significant differences between production. HDL cholesterol.88 –91 Thorne et al randomized 50 subjects phages. had a statistically significant improvement cytes in mice.83. a There is widespread support in the literature for the conclu. During weight loss.79 – 81 control and omentectomized patients at baseline. and decreased in triglyceride factor. 60 adipose tissue. Adi. in animals and humans is associated with increased in insulin binding epidermal growth factor. a proliferation in a receptor-independent fashion by binding to. In a cross-sectional analysis of 1356 women. to be derived from adipose sites.69 As might be expected based abdominal liposuction. Subjects with normal glucose tolerance lost approximately 9 lates expression of adhesion molecules on endothelial cells kg of fat (an 18% decrease in total fat). and in. and 10 to 12 weeks after. or lipid concentrations. IL-6. the activity of growth factors. Although the basis for the apparent difference in vascular fat tissue change in the leg correlated with worsening of CHD risk conferred by different adipose tissue depots remains risk factors. An increase in carotid intima/ confers more cardiovascular risk than peripheral adiposity (ie. with a more proatherogenic influence of the latter. and recent data suggest that CRP may be to 85 years of age.93 Central fat was positively associ- activator inhibitor-1 can promote atherothrombosis. and 28% in those with diabetes. and platelet-derived growth factor-BB. wall. Okura et al86 examined 128 tissue as measured by abdominal CT. At 2-year Obesity leads to increased expression of additional inflam. The expression of adipose tissue IL-6 is increased in There were no differences in blood lipids between the 2 human obesity.82 CD11B is a component of MAC-1 and is in oral glucose tolerance. plasma glu- tin. subsample of 310 participants underwent measurement of sion that central adiposity (fat in the trunk and/or abdomen) carotid intima/media thickness. loss intervention with diet and exercise. basic fibroblast growth sensitivity. independent and dominant antiatherogenic effect in elderly minogen activator inhibitor-1 are also produced by adipose women. sion and function in vessel wall cells. fasting plasma involved in binding of monocyte/macrophages to the vascular glucose.92 aortic calcification (as an index of directly involved in atherogenesis at the vessel wall.84 atherosclerosis) was evaluated. metabolic profile in both groups.14. adiponectin reduces by on March 17. CRP may also be produced in cular disease. It also did not thelial cells have been reported in response to adiponec. insulin sensitivity.

This study is important underlying diseases that cause unintentional weight loss. lipids. differentially expressed in the 2 depots. The development and evaluation of additional disease and measured parameters of vascular structure. mostly by macrophages. There have been multiple studies demonstrating improve. there were no direct measures of macrovascular such data are the limited therapeutic success for producing disease reported for this study. low HDL. free fatty can produce more substantial long-term weight loss. and this may be at least partly related to a less favorable ment in metabolic or inflammatory markers with short-term pattern of adipokines and cytokines released by visceral fat weight loss. obese persons who have lost weight are not lower compared hypertriglyceridemia. There were the expected improvements in total tissue and 216 were more abundant in visceral fat. blood pressure. loss on cardiovascular events. May 2007 al recently performed a microarray analysis of genes differ. the results of studies evaluating the subjects. Sjostrom acids. Several plausible mechanisms exist for a showing differences in cardiovascular outcomes. which infiltrate negative caloric balance improved carotid distensibility in adipose tissue in greater number in obese compared with lean obese men.102 group. vascular endothelial growth did not change. has been shown to be produced at trol group.106 can directly impact the atherogenic environment of the vessel Lifestyle interventions can produce an average net reduction wall by regulating gene expression and function in endothe- of 5.107 Only a few weight lial. tion. body com- tissue of obese subjects and identified 347 genes that were position. After 6 months. and systemic inflammation. MCP-1.13.1000 Arterioscler Thromb Vasc Biol.1% in the surgery tissue. These metaanalysis of trials testing the effect of weight loss medi. During weight loss. and insulin sensi- pared with subcutaneous tissue. and mechanical properties using ultrasound. likely magnifying involving obese subjects who underwent gastric surgery the adverse consequences of excess visceral adipose tissue. Dengel et al have recently studied 12 successfully meeting the challenge presented by the epidemic overweight individuals without known diabetes or vascular of obesity. addition to creating a more proinflammatory environment.8% over an average of 67 weeks. The surgical Observational studies have shown that mortality rates among group also had lower 2. endothelial function and arterial intima/media thickness including IL-6.6% for sibutramine at 1 year. The absence of a differences in the incidence of hypercholesterolemia or hy- reduction in mortality in these studies has been attributed to pertension between the groups. or to because it demonstrates that the improvements in the meta- the adverse effect of repeated weight cycling. and longer-term studies with sustained weight loss thereby creating a self-sustaining inflammatory cycle. arterial smooth muscle.105. especially recently been proposed as a loss of at least 10% of body among the young.6% in higher levels in subcutaneous compared with visceral adipose the control group and decreased by16.111 After 10 years. cholesterol. however.and 10-year rates of recovery from diabetes. In a recent causative role for obesity in producing atherosclerosis. There were no with those who have not lost weight.108 –110 There have.ahajournals. ever.96 Com. func. and hyperuricemia. are mixed.100 Increased levels of the chemokine MCP-1 in effect of weight loss on measures of macrovascular disease visceral adipose tissue attract more monocytes/macrophages. triglyceride.100 In are needed.and 10-year incidence of diabetes. visceral adipose tissue pro.103 confers more vascular and metabolic risk than peripheral fat. hypertriglyceridemia. the vascular response to L-arginine improved in these factors are produced by the stromovascular fraction of obese by on March 17. and lipids were also measured.97–99 Many of weight loss. One problem with obtaining However.103 Clearly. glucose metabo- cations. Two. tivity.110 Overall. and macrophage cells.101 compared with a matched conventionally treated obese con- Leptin. loss of almost any atherosclerosis and consequent cardiovascular disease in the amount of weight for only 1 year would have limitations for coming decades. a definition of successful weight loss maintenance has The recent increase in the prevalence of obesity.109 Balkestein et al reported that 3 months of adipose tissue. on the other hand.108 An entially expressed in subcutaneous versus visceral adipose intravenous glucose-tolerance test.9% was lism. also substantial support in the literature that adipose tissue and. and hormones—also gain a direct access to the liver et al recently reported on a prospective controlled study through the portal circulation (Figure 1). has significant implications for rates of weight for at least 1 year. a net reduction from baseline weight of 2.85. hypertension. weight had increased by 1. In addition. reports of the effects of weight loss on direct measures of Important questions for additional research remain for macrovascular disease. IL-8.104 emerging that factors produced by adipose tissue in obesity Similar effects have been reported for rimonabant. ments in brachial artery compliance and distensibility. There are no bolic parameters that have been repeatedly demonstrated in interventional studies demonstrating the benefit of weight short-term weight loss are durable for up to 10 years. been fewer and its favored access to the portal circulation. how- cated in cardiovascular disease and metabolic disturbances. LDL cholesterol. among these. evidence is shown for orlistat and 4. There is loss studies have followed subjects for longer than 1 year. include changes in blood pressure. and hyperuri- Cardiovascular Benefits of Weight Loss cemia were more favorable in the surgery group. 2010 . tools for prevention and treatment of obesity and its vascular Downloaded from atvb. significant long-term weight loss in obese individuals. of which 131 genes there were significant reductions in BMI and percentage of were expressed at higher levels in subcutaneous adipose body fat. approximately 15% to 20% of individuals distribution is important for atherosclerotic risk. and plasminogen activator inhibitor-1. Per- haps reflecting the limitations of current therapeutic interven. Truncal fat maintain a weight loss of at least 5 kg or more at 5 years. As compared with medical therapy. there were also significant improve- duces higher levels of several factors that have been impli.31. Ziccardi et al reported that after 1 year of factor. surgical intervention products of visceral adipose tissue— cytokines.12. Conclusion tions.

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