Cannabinoid-1 receptor antagonists in type-2 diabetes

Type-2 diabetes is closely related to abdominal obesity and is generally associated with other cardiometabolic risk factors, resulting in a risk of major cardiovascular disease. Several animal and human observations suggest that the endocannabinoid system is over-active in the presence of abdominal obesity and/or diabetes. Both central and peripheral endocannabinoid actions, via the activation of CB1 receptors, promote weight gain and associated metabolic changes. Rimonabant, the first selective CB(1) receptor blocker in clinical use, has been shown to reduce body weight, waist circumference, triglycerides, blood pressure, insulin resistance index and C-reactive protein levels, and to increase high-density lipoprotein (HDL) cholesterol and adiponectin concentrations in both non-diabetic and diabetic overweight/obese patients. In addition, a 0.5-0.7% reduction in HbA1c levels was observed in metformin- or sulphonylurea-treated patients with type-2 diabetes and in drug-na?ve diabetic patients. Almost half of the metabolic changes, including HbA1c reduction, could not be explained by weight loss, suggesting that there are direct peripheral effects. Rimonabant was generally well-tolerated, and the safety profile was similar in diabetic and non-diabetic patients, with a higher incidence of depressed mood disorders, nausea and dizziness. In conclusion, the potential role of rimonabant in overweight/obese patients with type-2 diabetes and at high risk of cardiovascular disease deserves much consideration.     

Greater beneficial effects of visceral fat reduction compared with subcutaneous fat reduction on parameters of the metabolic syndrome: a study of weight reduction programmes in subjects with visceral and subcutaneous obesity.

AIMS: To evaluate the effect of weight reduction on parameters of the metabolic syndrome in obese patients according to their pattern of abdominal fat distribution. METHODS: A longitudinal intervention study, consisting of a 12-week weight reduction programme, including lifestyle modification and adjuvant appetite suppressant, in 38 subjects with visceral obesity and 47 subjects with subcutaneous obesity. Visceral, subcutaneous and total adipose tissue areas were determined by CT scan at the level of L4-L5. Parameters for components of the metabolic syndrome were measured before and after weight reduction. RESULTS: Reductions in body weight, BMI and subcutaneous adipose tissue area were greater in the subcutaneous than in the visceral obesity group. In contrast, changes in fasting plasma glucose, insulin, and HOMA score were higher in the visceral than in the subcutaneous obesity group. Changes in visceral adipose tissue area were significantly related to changes in fasting plasma glucose, triglycerides and HOMA score. CONCLUSIONS: Visceral fat reduction induced greater beneficial effects on parameters of the metabolic syndrome than subcutaneous fat reduction. Evaluation of changes in abdominal fat distribution is necessary when obese subjects enter a weight reduction programme.     

Telmisartan prevents obesity and increases the expression of uncoupling protein 1 in diet-induced obese mice

The aim of the present study was to clarify the effect of telmisartan, an angiotensin II receptor blocker, on the development of obesity and related metabolic disorders in diet-induced obese mice. Treatment with telmisartan dissolved in drinking water at a dosage of 5 mg/kg per day for 14 days attenuated the diet-induced weight gain without affecting food intake in diet-induced obese mice compared with controls using nontreated water. Telmisartan treatment decreased the weight of visceral adipose tissue and the triglyceride content in the liver and skeletal muscle. In addition, hyperglycemia, hyperinsulinemia, and hypertriglyceridemia in diet-induced obese mice all improved with telmisartan treatment. Furthermore, telmisartan treatment increased adiponectin mRNA in visceral white adipose tissue and was associated with a concomitant change in the serum adiponectin level. In contrast, the treatment reduced the serum level of resistin. Finally, telmisartan treatment increased the mRNA expression of uncoupling protein 1 in brown adipose tissue and was accompanied by an increase in oxygen consumption. In conclusion, telmisartan treatment might prevent the development of obesity and related metabolic disorders by altering the levels of adiponectin, resistin, and uncoupling protein 1 in diet-induced obese mice. Our results indicate that telmisartan can be used as a therapeutic tool for metabolic syndrome, including visceral obesity.     

The value of current interventions for obesity

Obesity greatly increases risk of cardiovascular disease, metabolic syndrome, and diabetes mellitus. Most obese patients are unable to sustain appreciable weight loss; the body has a natural tendency to return to its previous weight. Although bariatric surgery is effective, it is not without risk. Until better treatments for obesity are available, management remains focused on lifestyle changes, drug therapy, and treating the metabolic complications of obesity. The main cause of metabolic dysfunction in obesity is visceral fat. Fat deposition in and around organs, skeletal muscle, and other tissues is thought to occur when subcutaneous adipose tissue stores are full. Creation of additional adipose-tissue stores is prevented by the mature adipocytes, which inhibit the differentiation of preadipocytes in a negative feedback loop. This inhibition is mediated, in part, by the renin-angiotensin system. Indeed, angiotensin II blockade has been shown to promote adipogenesis in vitro. Clinical studies are currently underway to investigate whether the angiotensin-II-receptor blocker telmisartan can stimulate adipogenesis, with the aim of diverting intramuscular fat back into adipose tissue and thereby restoring insulin sensitivity. If this effect can be demonstrated in humans, this type of agent might become the treatment of choice for obese or overweight people at risk of type 2 diabetes.     

Growth hormone treatment reduces abdominal visceral fat in postmenopausal women with abdominal obesity: a 12-month placebo-controlled trial

Abdominal obesity is associated with blunted GH secretion and a cluster of cardiovascular risk factors that characterize the metabolic syndrome. GH treatment in abdominally obese men reduces visceral adipose tissue and has beneficial effects on the metabolic profile. There are no long-term data on the effects of GH treatment on postmenopausal women with abdominal obesity. Forty postmenopausal women with abdominal obesity participated in a randomized, double-blind, placebo-controlled, 12-month trial with GH (0.67 mg/d). The primary aim was to study the effect of GH treatment on insulin sensitivity. Measurements of glucose disposal rate (GDR) using a euglycemic, hyperinsulinemic glucose clamp; abdominal fat, hepatic fat content, and thigh muscle area using computed tomography; and total body fat and fat-free mass derived from (40)K measurements were performed at baseline and at 6 and 12 months. GH treatment reduced visceral fat mass, increased thigh muscle area, and reduced total and low-density lipoprotein cholesterol compared with placebo. Insulin sensitivity was increased at 12 months compared with baseline values in the GH-treated group. In the GH-treated group only, a low baseline GDR was correlated with a more marked improvement in insulin sensitivity (r = -0.68; P < 0.001). A positive correlation was found between changes in GDR and liver attenuation as a measure of hepatic fat content between baseline and 12 months (r = 0.7; P < 0.001) in the GH-treated group. In postmenopausal women with abdominal obesity, 1 yr of GH treatment improved insulin sensitivity and reduced abdominal visceral fat and total and low-density lipoprotein cholesterol concentrations. The improvement in insulin sensitivity was associated with reduced hepatic fat content.     

Relationships between changes in abdominal fat distribution and insulin sensitivity during a very low calorie diet in abdominally obese men and women

BACKGROUND AND AIM: Little is known about the association between abdominal obesity and insulin sensitivity during rapid weight loss. We assessed the role of visceral and subcutaneous fat as determinants of insulin sensitivity during rapid weight loss in obese persons with the metabolic syndrome. METHODS AND RESULTS: Twenty abdominally obese individuals [11 women and 9 men, body mass index (BMI) 35.8+/-3.5 kg/m2] with the metabolic syndrome underwent a very-low-calorie diet (VLCD) for nine weeks. At baseline, the computed tomography (CT) measured area of total (r=-0.50, p=0.033) and visceral fat tissue (r=-0.48, p=0.043), but not that of subcutaneous fat tissue (r=-0.34, p=0.17), correlated with insulin sensitivity as assessed by the quantitative insulin sensitivity check index after adjusting for sex and age. The 18 subjects who completed the study lost 14.8 kg during the VLCD. Total, visceral and subcutaneous abdominal fat tissue decreased by 22%, 29% and 17%, respectively. The decrease in total (r=-0.51, p=0.035) and subcutaneous abdominal fat (r=-0.57, p=0.017), but not visceral fat (r=0.11, p=0.68), correlated with the increase in insulin sensitivity. Waist circumference did not offer any additional information concerning abdominal fat distribution or insulin sensitivity compared with that provided by BMI at baseline or after weight loss. The waist/hip ratio was not associated with the CT measures of abdominal fat distribution or insulin sensitivity. CONCLUSIONS: Total abdominal fat may be more important than its compartmentalisation in abdominally obese individuals with the metabolic syndrome. In this subgroup of individuals with obesity, the measurement of waist circumference and the waist/hip ratio offered little additional information over that provided by BMI at baseline or after weight loss.     

Expression of the mRNA coding for 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue from obese patients: an in situ hybridization study

Glucocorticoids play an important role in determining adipose tissue metabolism and distribution. Patients with Cushing's syndrome or receiving corticosteroid therapy develop a reversible visceral obesity. In obese patients, although circulating concentrations of cortisol are not consistently elevated, local conversion of inactive cortisone to active cortisol in adipose tissue, catalyzed by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1), could amplify glucocorticoid signaling. We have studied, using semiquantitative in situ hybridization, 11beta-HSD-1 mRNA expression in the adipocyte and stromal compartments of sc abdominal adipose tissue obtained from 12 lean patients and sc abdominal and visceral adipose tissue obtained from 18 obese patients. 11beta-HSD-1 mRNA was expressed in adipocytes, stroma, and walls of vessels. Localization of 11beta-HSD-1 mRNA did not differ between lean sc and obese sc or visceral adipose tissue. 11beta-HSD-1 mRNA levels were significantly (P = 0.0106) increased in the adipocyte compartment of sc adipose tissue obtained from obese patients as compared with nonobese ones, whereas no significant change (P = 0.446) was found in the stromal compartment. In obese patients, 11beta-HSD-1 mRNA expression was increased (P = 0.0157) in the stromal compartment of visceral compared with sc tissue, whereas no significant change (P = 0.8767) was found in the adipocyte compartment. In summary, our data show that 11beta-HSD-1 mRNA is increased in adipose tissue from obese patients, in the abdominal sc fat in adipocytes and in the visceral fat in both adipocytes and stroma. This observation suggests that an overexpression of 11beta-HSD-1 may explain part of the glucocorticoid-induced metabolic disorders linked to obesity and may promote visceral fat deposition.     

Circulating levels of oxidative stress markers and endothelial adhesion molecules in men with abdominal obesity

CONTEXT: It has been suggested that oxidative stress and endothelial dysfunction could play a role in the higher cardiovascular disease risk noted in the abdominally obese population. OBJECTIVE: The objective of this study was to describe the associations between abdominal fat accumulation, oxidative stress, and endothelial dysfunction in men. DESIGN: A complete physical and metabolic profile was assessed in a group of 56 men covering a wide range of adiposity and plasma oxidized low-density lipoprotein (OxLDL), and soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, E-selectin, and C-reactive protein concentrations were determined. RESULTS: We found that abdominal visceral adipose tissue was positively associated with plasma OxLDL (r = 0.52; P < 0.0001) and C-reactive protein (r = 0.60; P < 0.0001) concentrations. We also found significant associations between plasma E-selectin levels and hyperinsulinemia (r = 0.39; P < 0.005) as well as with the homeostasis model assessment index of insulin resistance (r = 0.42; P < 0.005). CONCLUSIONS: Our study showed that plasma OxLDL levels and low-grade systemic inflammation are increased in men with a high visceral adipose tissue accumulation. Furthermore, our results support the notion that insulin resistance is associated with endothelial activation. Overall, our observations give us further insights on the increased cardiovascular disease risk frequently noted among viscerally obese, insulin-resistant individuals.     

Rimonabant: a cannabinoid receptor type 1 blocker for management of multiple cardiometabolic risk factors.

Rimonabant is a first selective blocker of the cannabinoid receptor type 1 (CB1) being developed for the treatment of multiple cardiometabolic risk factors, including abdominal obesity and smoking. In four large trials, after one year of treatment, rimonabant 20 mg led to greater weight loss and reduction in waist circumference compared with placebo. Therapy with rimonabant is also associated with favorable changes in serum lipid levels and an improvement in glycemic control in prediabetes patients and in type 2 diabetic patients. At the same dose, rimonabant significantly increased cigarette smoking quit rates as compared with placebo. Rimonabant seems to be well tolerated, with a primary side effect of mild nausea. As an agent with a novel mechanism of action, rimonabant has a potential to be a useful adjunct to lifestyle and behavior modification in treatment of multiple cardiometabolic risk factors, including abdominal obesity and smoking.     

Rimonabant: a cannabinoid receptor type 1 blocker for management of multiple cardiometabolic risk factors

Rimonabant is a first selective blocker of the cannabinoid receptor type 1 (CB1) being developed for the treatment of multiple cardiometabolic risk factors, including abdominal obesity and smoking. In four large trials, after one year of treatment, rimonabant 20 mg led to greater weight loss and reduction in waist circumference compared with placebo. Therapy with rimonabant is also associated with favorable changes in serum lipid levels and an improvement in glycemic control in prediabetes patients and in type 2 diabetic patients. At the same dose, rimonabant significantly increased cigarette smoking quit rates as compared with placebo. Rimonabant seems to be well tolerated, with a primary side effect of mild nausea. As an agent with a novel mechanism of action, rimonabant has a potential to be a useful adjunct to lifestyle and behavior modification in treatment of multiple cardiometabolic risk factors, including abdominal obesity and smoking.     

Dyslipidemia and abdominal obesity: therapeutic approaches (Part II)

Lifestyle changes form the basis of the therapeutic management of dyslipidemia associated with abdominal obesity and other risk factors associated with an excess of visceral adipose tissue. The use of lipid-lowering agents is justified if the therapeutic objectives are not attained by lifestyle changes alone. New therapeutic approaches are aimed directly at the excess visceral adipose tissue, and the CB1 receptor blockers are particularly promising for improving the overall lipid profile for patients with abdominal obesity.     

Abdominal Obesity and Cardiovascular Disease: Is Inflammation the Missing Link?

It is well established that cardiovascular disease has an inflammatory component. The present narrative review explores the role of adipose tissue distribution, morphology, and function as potential mediators of the link between inflammation and cardiovascular disease. Evidence that abdominal obesity is a key driving force behind a constellation of atherothrombotic inflammatory abnormalities linked to insulin resistance and often referred to as the metabolic syndrome is also reviewed. It is also proposed that the amount of visceral adipose tissue and the liver fat content are important factors responsible for the link between abdominal obesity and features of the metabolic syndrome. It is suggested that the inflammatory profile associated with excess visceral adipose tissue/liver fat may be a consequence of the relative inability of subcutaneous adipose tissue to expand through hyperplasia and to act as a protective metabolic sink storing the chronic energy surplus resulting from a positive energy balance (overnutrition or lack of physical activity or both). In this model, the inflammatory profile often observed among sedentary overweight/obese individuals with an excess of visceral adipose tissue/liver fat may be a consequence of a more primary defect in subcutaneous adipose tissue. On that basis, it is proposed that therapeutic strategies relieving the stress for storage of a chronic energy surplus in the subcutaneous adipose tissue (reduced caloric intake, increase in energy expenditure, pharmacotherapy) should induce a substantial loss of visceral adipose tissue and of ectopic fat depots such as the liver, thereby substantially reducing inflammation.     

Adipose tissue: a mediator of cardiovascular risk

Two key findings regarding the cardiovascular risks associated with obesity have emerged in recent years: one relates to the importance of visceral obesity as a risk factor for cardiovascular disease, and the other to the recognition that adipose tissue can be regarded as a large endocrine organ that directly contributes to cardiovascular risk by secreting a number of molecules known to modulate vascular, metabolic, inflammatory and other functional aspects of the cardiovascular system. Therefore, abdominal fat deposition, which is characterized by increase in waist circumference, should be the target of clinical intervention in obese individuals.     

Improvement of glucose and lipid metabolism associated with selective reduction of intra-abdominal visceral fat in premenopausal women with visceral fat obesity.

Visceral fat obesity (VFO) with predominant intra-abdominal fat accumulation has been shown to be more often associated with metabolic disorders than subcutaneous fat obesity (SFO). In the present study, changes in fat distribution and their effects on metabolic complications were investigated in forty premenopausal female obese patients in whom substantial weight reduction was obtained by means of a low calorie diet. Analysis of fat distribution by CT scanning demonstrated that visceral fat decreased to a greater extent than abdominal subcutaneous fat, which was particularly evident in VFO patients. On the other hand, change of fat distribution was small in SFO patients. That is, visceral to subcutaneous abdominal fat ratio (V/S ratio) decreased from 0.62 +/- 0.36 to 0.46 +/- 0.33 in VFO, whereas from 0.23 +/- 0.07 to 0.20 +/- 0.09 in SFO after weight reduction. Although obese patients, especially those with VFO, were frequently associated with glucose intolerance and hyperlipidemia, marked diminution was observed in the elevated levels of plasma glucose area on 75g OGTT, serum total cholesterol and triglyceride after weight reduction. By the examination of interrelationship between the changes in body weight, BMI, total and regional fat volume and changes in glucose and lipid metabolism, we found that the decrease in the V/S ratio and visceral fat volume were more strongly correlated with the improvement in plasma glucose and lipid metabolism compared to the decrease in body weight, BMI, total fat volume and abdominal subcutaneous fat volume. Furthermore, partial correlation analyses demonstrated that the metabolic improvements were associated with changes in visceral abdominal fat after control for changes in total adipose tissue volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adrenal and gonadal function in obesity

Obesity is associated with multiple alterations of the endocrine systems, including abnormal circulating blood hormone concentrations, due to changes in their pattern of secretion and/or metabolism, altered hormone transport, and/or action at the level of target tissues. There is evidence that alterations of endocrine systems regulating sex hormones and corticosteroids may play a crucial role in the development of obesity, particularly the abdominal phenotype. Obese women are characterized by a condition of sc"functional hyperandrogenism", whereas in males, obesity is associated with reduced T levels and decreased LH secretory pattern from the pituitary. In addition, in both sexes a dysregulation of the hypothalamic-pituitary-adrenal axis has been reported, including both neuroendocrine and peripheral alterations, finally leading to inappropriately higher than normal exposure to F of peripheral tissues, particularly the visceral adipose tissue. By these mechanisms, it can be hypothesized that both visceral fat enlargement and alterations of insulin action and associated metabolic disturbances may develop, therefore predisposing abdominally obese individuals to Type 2 diabetes and cardiovascular disease.     

Visceral, subcutaneous or intramuscular fat: where is the problem?

The adipose tissue is a dynamic organ that secrets several factors, denominated adipokines. They are associated, directly or indirectly, in a process that contributes to atherosclerosis, hypertension, insulinic resistance and diabetes type 2, dyslipidemias, presenting the link between adiposity, metabolic syndrome and cardiovascular diseases. In the obesity, body fat depots are increased, presenting eventual elevation in the adipokines expression and secretion. The different fat depots, visceral, abdominal subcutaneous, gluteal-femoral subcutaneous and intramuscular adipose tissue, have different metabolic and endocrine degrees, interfering, therefore, with specific form in the process associated with body adiposity in obese and diabetics subjects. The present study seeks to discuss the endocrine and metabolic role of each adipose tissue compartment, by way to assess their contribution to the complications linked to obesity.     

Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk

There is currently substantial confusion between the conceptual definition of the metabolic syndrome and the clinical screening parameters and cut-off values proposed by various organizations (NCEP-ATP III, IDF, WHO, etc) to identify individuals with the metabolic syndrome. Although it is clear that in vivo insulin resistance is a key abnormality associated with an atherogenic, prothrombotic, and inflammatory profile which has been named by some the "metabolic syndrome" or by others "syndrome X" or "insulin resistance syndrome", it is more and more recognized that the most prevalent form of this constellation of metabolic abnormalities linked to insulin resistance is found in patients with abdominal obesity, especially with an excess of intra-abdominal or visceral adipose tissue. We have previously proposed that visceral obesity may represent a clinical intermediate phenotype reflecting the relative inability of subcutaneous adipose tissue to act as a protective metabolic sink for the clearance and storage of the extra energy derived from dietary triglycerides, leading to ectopic fat deposition in visceral adipose depots, skeletal muscle, liver, heart, etc. Thus, visceral obesity may partly be a marker of a dysmetabolic state and partly a cause of the metabolic syndrome. Although waist circumference is a better marker of abdominal fat accumulation than the body mass index, an elevated waistline alone is not sufficient to diagnose visceral obesity and we have proposed that an elevated fasting triglyceride concentration could represent, when waist circumference is increased, a simple clinical marker of excess visceral/ectopic fat. Finally, a clinical diagnosis of visceral obesity, insulin resistance, or of the metabolic syndrome is not sufficient to assess global risk of cardiovascular disease. To achieve this goal, physicians should first pay attention to the classical risk factors while also considering the additional risk resulting from the presence of abdominal obesity and the metabolic syndrome, such global risk being defined as cardiometabolic risk.     

Abdominal obesity,muscle composition,and insulin resistance in premenopausal women

The independent relationships between visceral and abdominal sc adipose tissue (AT) depots, muscle composition, and insulin sensitivity were examined in 40 abdominally obese, premenopausal women. Measurements included glucose disposal by euglycemic clamp, muscle composition by computed tomography, abdominal and nonabdominal (e.g. leg) AT by magnetic resonance imaging and cardiovascular fitness. Glucose disposal rates were negatively related to visceral AT mass (r = -0.42, P < 0.01). These observations remained significant (P < 0.01) after control for nonabdominal and abdominal sc AT, muscle attenuation, and peak oxygen uptake. Total, abdominal, or leg sc AT or muscle attenuation was not significantly (P > 0.10) related to glucose disposal. Subdivision of abdominal sc AT into anterior and posterior depots did not alter the observed relationships. Further analysis matched two groups of women for abdominal sc AT but with low and high visceral AT. Women with high visceral AT had lower glucose disposal rates compared with those with low visceral AT (P < 0.05). A similar analysis performed on two groups of women matched for visceral AT but high and low abdominal sc AT revealed no statistically different values for insulin sensitivity (P > 0.10). In conclusion, visceral AT alone is a strong correlate of insulin resistance independent of nonabdominal, abdominal sc AT, muscle composition, and cardiovascular fitness. Subdivision of abdominal sc AT did not provide additional insight into the relationship between abdominal obesity and metabolic risk.     

Obesity and post‐operative complications in patients undergoing non‐bariatric surgery

As the prevalence of obesity continues to rise in society, an increasing number of patients undergoing non‐bariatric surgery will be obese. Obesity is known to increase morbidity and mortality in the general population and thus is perceived as a risk factor for adverse post‐surgical outcomes. This association is not clear‐cut, however, and there is a lack of consensus in the literature on the risk between obesity and specific complications, in particular relating to infection, wound healing, respiratory and venous thromboembolism. The paucity of studies, as well as a lack of consistency of definition of obesity, with an over‐reliance on body mass index rather than body composition analysis, may underlie this confusion. Emerging concepts position central/visceral adipose tissue as potentially key to the pathogenesis of the comorbidities associated with obesity, thus this article reviews emerging research investigating the association between visceral obesity, the metabolic syndrome and resulting post‐operative complications. It is hypothesized that the state of chronic inflammation and dysmetabolism observed in visceral obese patients negatively influences post‐operative outcomes and represents a potential target for pharmaconutrition. The need for further research investigating the influence of visceral adiposity on immune function post surgery and its impact on post‐operative morbidity and mortality is highlighted.     

WILLENDORF AWARDAW0001Establishment of the concept of visceral fat syndrome and the discovery of adiponectin

Clinical studies in recent years have demonstrated that the extent of obesity does not necessarily determine the development of obesity‐related diseases such as type2 diabetes, hyperlipidemia, hypertension, but fat distribution is a much more important determinant In 1983, we reported a method for fat analysis using CT scan which enabled us to analyze in intraabdominal adipose tissue, namely visceral fat as well as subcutaneous fat. Then we demonstrated that visceral fat accumulation correlated to the disturbance of lipid and glucose metabolism, insulin resistance, hypertension and cardiovascular disease in obese subjects and even in non‐obese subjects. From these clinical studies, we proposed the concept of ‘visceral fat syndrome’ in which multiple risk factors cluster through visceral fat accumulation. Besides, this syndrome is designated to be a very atherogenic state. Visceral fat syndrome is corresponding to the concept of metabolic syndrome recently noted. In order to clarify the molecular mechanism why visceral fat accumulation correlates to plural common diseases and also directly to atherosclerosis, we started a project for the analysis of adipose tissue using random sequence of expressed genes in adipose tissues. We found unexpectedly that adipose tissue, especially visceral fat, expressed strongly the genes encoding secretory proteins most of which are important bioactive substances (named as adipocytokines). In addition to known adipocytokines, several novel adipose‐specific genes were identified. Among them, a collagen‐like protein encoded by an adipose most abundant gene (apM‐1) is the most important novel adipocytokine which is named adiponectin. Adiponectin has anti‐diabetic, anti‐atherogenic, anti‐oncogenic and anti‐inflammatory properties and its plasma levels decreases with visceral fat accumulation, suggesting that this molecules may play a central role in the visceral fat syndrome or metabolic syndrome. In this lecture, I would like to present the importance of adiponectin together with other adipocytokines in lifestyle‐related diseases relevant to visceral fat accumulation.