Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0311277 (abdominal obesity)
 2,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endocannabinoid system is overactivated in individuals with abdominal obesity. CBI receptors, first individualized in the brain, are also expressed in the adipocyte, the skeletal muscle, the liver, the gut, and the pancreas. Their blockade improves glucose tolerance and lipid profile, thanks increased insulin sensitivity and adiponectin levels. Rimonabant, a selective antagonist of CBI receptors, improves glucose control in patients with type 2 diabetes, treated with diet alone, metformin, sulfonylurea or insulin, while it also reduces body weight and other risk factors. Ongoing studies aim at further demonstrating the potential of rimonabant in the management of type 2 diabetes, in the prevention of type 2 diabetes and in the protection against cardiovascular complications in (diabetic) patients with abdominal obesity.
 ...
PMID:[CB1 receptor inhibition and glucose metabolism: role of rimonabant in type 2 diabetes]. 1881 65

It has been hypothesized that abdominal obesity leads to insulin resistance partly through decreased adiponectin. However, the cross-sectional and longitudinal associations among waist, adiponectin, and insulin sensitivity have not been examined in older adolescents. Non-Hispanic white and black children were recruited from the Minneapolis school district and underwent three examinations at mean ages 13, 15, and 19. Insulin sensitivity (measured using the gold-standard euglycemic clamp) and waist circumference were measured at all exams. Adiponectin was measured at mean ages 15 and 19. Partial correlations were used to examine associations among waist, adiponectin, and insulin sensitivity at mean age 15 (n = 308) and mean age 19 (n = 218). Longitudinal correlations and a longitudinal regression model were used to predict adiponectin and insulin sensitivity measured at ages 15 and 19, from age 13 waist and change in waist. At age 15, waist and adiponectin were significantly correlated (r = -0.32). At age 19, waist and adiponectin were significantly correlated (r = -0.36), as were waist and insulin sensitivity (r = -0.16). Both baseline waist and change in waist were significantly inversely associated with age 19 adiponectin but with age 19 insulin sensitivity only in men. In conclusion, in adolescents, the association between waist and adiponectin appears to develop several years before the association between waist and insulin sensitivity and there is a longitudinal association between waist and adiponectin. These results support the hypothesis that adiponectin may contribute to the association of waist and insulin sensitivity.
 ...
PMID:Influence of waist on adiponectin and insulin sensitivity in adolescence. 1910 28

Adiponectin is a peptide hormone secreted by adipose tissue. It is a key hormone responsible for insulin sensitization, and its circulating level is inversely associated with abdominal obesity. Recent studies have shown that a reduced plasma adiponectin level is significantly correlated with the risk of various cancers. However, there are few studies regarding the association of adiponectin and colorectal cancer. To address this issue, we investigated the effect of adiponectin on colorectal cancer cells. Three colorectal cancer cell lines express both AdipoR1 and AdipoR2 receptors. MTT assay revealed that adiponectin inhibited human colorectal cancer cell growth. Furthermore, Western blot analysis revealed that adiponectin activated adenosine monophosphate-activated protein kinase (AMPK) and suppressed mammalian target of rapamycin (mTOR) pathways. Selective AMPK inhibitor compound C abrogated the inhibitory effect of adiponectin on cell growth. Our results clearly demonstrate the novel findings that adiponectin inhibits colorectal cancer cell growth via activation of AMPK, thereby down-regulating the mTOR pathway.
 ...
PMID:Adiponectin inhibits colorectal cancer cell growth through the AMPK/mTOR pathway. 1914 67

Abdominal obesity (high waist circumference) is more strongly associated with cardiovascular disease and type 2 diabetes than generalized adiposity (high body mass index). Recent research has highlighted the role of chronic overactivation of the endogenous endocannabinoid system, acting through its CB(1) receptor, as a key factor involved in the development of abdominal obesity and related cardiometabolic risk abnormalities such as insulin resistance, low HDL-cholesterol, hypertriglyceridemia, inflammation and low adiponectin. Evidence suggests that these cardiometabolic risk factors/markers are not optimally managed by current treatments. Improving the nutrition and physical activity/exercise habits of patients remains the cornerstone of management of elevated global cardiometabolic risk. Antagonism of the endocannabinoid system provides a novel strategy to target several unaddressed cardiometabolic risk markers/factors. Randomized trials of rimonabant in patients with overweight or obesity and/or type 2 diabetes have demonstrated marked and significant improvements in body weight, waist circumference, glycemic control (in patients with type 2 diabetes), features of atherogenic dyslipidemia, insulin resistance, adipose tissue-derived cytokines (leptin and adiponectin) and C-reactive protein (a marker of systemic inflammation). Further analyses suggested that about half of the improvements of several cardiometabolic risk markers were independent from concomitant weight loss. Blood pressure also improved with rimonabant treatment, this effect being consistent with the blood pressure lowering effect of weight loss. The tolerability and safety of rimonabant have been extensively studied and most transient side effects include some gastrointestinal side effects, anxiety, mood changes and incidence of depressive disorders, particularly in patients with previous history of depression. Rimonabant is a useful option for patients with abdominal obesity and with related cardiometabolic risk abnormalities such as an atherogenic dyslipidemia and/or type 2 diabetes.
 ...
PMID:Pleiotropic effects of rimonabant: clinical implications. 1919 81

We determined serum adiponectin's role as a biomarker of metabolic syndrome (MetS), type 2 diabetes (DM) and hypertension among Turkish adults who have a high prevalence of MetS. Individuals with measured serum adiponectin concentrations, constituting a random sample of Turkish adults, were studied cross-sectionally. MetS was identified by criteria of the Adult Treatment Panel-III modified for male abdominal obesity. Median age of 547 men and 652 women was 54 years. MetS was identified in 46%. Linear regression analysis among nine variables revealed homeostatic model assessment (HOMA) index in both sexes and C-reactive protein (CRP) only in men as inversely associated covariates of adiponectin, and sex hormone-binding globulin (SHBG) as positive covariate in women. Age-adjusted sex-specifically dichotomized high vs. low adiponectin levels were significantly associated with DM (odds ratio (OR) 0.55, P = 0.01) and hypertension (OR 0.64, P = 0.012) in women, but not in men. Further adjustment for smoking status and presence of high/low BMI did not alter this sex-based relationship. As regards association with MetS, low adiponectin and high BMI interacted significantly in each sex. Yet adiponectin was associated only in men additively to the simultaneously adjusted five MetS components. We conclude that adiponectin concentrations, clearly linked to metabolic disorders, may diverge among sexes regarding protection against cardiometabolic risk through anti-inflammatory or antioxidative function, Turkish men alone revealing significant dysfunction independent of obesity. This dysfunction may underlie also the association of adiponectin levels with MetS in men to be independent of the MetS components.
 ...
PMID:Serum adiponectin confers little protection against diabetes and hypertension in Turkish men. 1923 42

Type 2 diabetes is closely related to abdominal obesity and is generally associated with other cardiometabolic risk factors, resulting in a high incidence of cardiovascular complications. Several animal and human observations suggest that the endocannabinoid (EC) system is overactivated in presence of abdominal obesity and/or diabetes, and contributes to disturbances of energy balance and metabolism. Not only it regulates the intake of nutrients through central mechanisms located within the hypothalamus and limbic area, but it also intervenes in transport, metabolism and deposit of the nutrients in the digestive tract, liver, adipose tissue, skeletal muscle, and possibly pancreas. Activation of both central and peripheral CB1 receptors promotes weight gain and associated metabolic changes. Conversely, rimonabant, the first selective CB(1) receptor antagonist in clinical use, has been shown to reduce body weight, waist circumference, triglycerides, blood pressure, insulin resistance and C-reactive protein levels, and to increase HDL cholesterol and adiponectin concentrations in both non-diabetic and diabetic overweight/obese patients. In addition, a 0.5-0.7% reduction in glycated hemoglobin (HbA1c) levels was observed in metformin- or sulfonylurea-treated patients with type 2 diabetes and in drug-naive or insulin-treated diabetic patients. Almost half of metabolic changes occurred beyond weight loss, in agreement with direct peripheral effects. Rimonabant was generally well-tolerated, but with a slightly higher incidence of depressed mood disorders, anxiety, nausea and dizziness compared to placebo. New trials are supposed to confirm the potential role of rimonabant (and other CB1 neutral antagonists or inverse agonists) in overweight/obese patients with type 2 diabetes and high risk cardiovascular disease.
 ...
PMID:The endocannabinoid system: a promising target for the management of type 2 diabetes. 1927 73

Abdominal obesity is associated with numerous metabolic abnormalities, including insulin resistance, impaired glucose tolerance/type-2 diabetes, and atherogenic dyslipidaemia with low high-density lipoprotein (HDL) cholesterol, high triglycerides, and increased small dense low-density lipoprotein (LDL) cholesterol. A proportion of these metabolic disorders may be attributed to increased endocannabinoid activity. The selective cannabinoid 1 (CB1) receptor antagonist rimonabant has been shown to reduce body weight, waist circumference, insulin resistance, triglycerides, dense LDL, C-reactive protein (CRP), and blood pressure, and to increase HDL and adiponectin concentrations in both non-diabetic and diabetic overweight/obese patients. Besides an improvement in glucose tolerance in non-diabetic subjects, a reduction of 0.5-0.7% in haemoglobin A1C (HbA(1c)) levels was consistently observed in various groups of patients with type-2 diabetes. Almost half the metabolic changes could not be explained by weight loss, supporting direct peripheral effects of rimonabant. Ongoing studies should demonstrate whether improved metabolic disorders with CB1 receptor antagonists (rimonabant, taranabant, etc.) would translate into fewer cardiovascular complications among high-risk individuals.
 ...
PMID:Use of cannabinoid CB1 receptor antagonists for the treatment of metabolic disorders. 1928 64

Insulin receptor substrate-1 (IRS-1) and glucose transporter 4 (GLUT4) expression may provide an indirect reflection of the capacity of adipocytes to respond to insulin stimulation. We examined messenger RNA (mRNA) expression of these genes in omental and subcutaneous adipose tissue of women. Paired omental and subcutaneous adipose tissue samples were obtained from 36 women (age, 47 +/- 5 years; body mass index, 28.0 +/- 5.4 kg/m(2)) undergoing gynecologic surgeries. Total adiposity and visceral adiposity were assessed by dual-energy x-ray absorptiometry and computed tomography. The GLUT4 and IRS-1 mRNA expression levels were both significantly higher in subcutaneous compared with omental adipose tissue. A negative correlation was observed between body fat percentage and subcutaneous adipose tissue GLUT4 (r = -0.39, P < .05) and IRS-1 (r = -0.30, P < .08) mRNA abundance. However, in omental fat, only GLUT4 mRNA was inversely associated with body fat percentage (r = -0.53, P < .001). Moreover, the homeostasis model assessment of insulin resistance index was associated with mRNA expression of subcutaneous GLUT4 (r = -0.56, P < .001), subcutaneous IRS-1 (r = -0.51, P < .01), and omental GLUT4 (r = -0.54, P < .001), but not omental IRS-1. Interestingly, plasma adiponectin was only associated with subcutaneous GLUT4 (r = 0.48, P < .01) and IRS-1 (r = 0.48, P < .05) mRNA expression. The GLUT4 protein, unlike mRNA expression, was higher in omental than in subcutaneous adipose tissue. However, abdominal obesity-related differences in protein or mRNA expression were similar. Omental IRS-1 expression was low and unaffected by visceral obesity. In contrast, omental and subcutaneous GLUT4 as well as subcutaneous IRS-1 were reduced in visceral obesity. This divergent pattern of expression may reflect a lower capacity of omental adipose tissue to respond to insulin stimulation at all adiposity levels.
 ...
PMID:Glucose transporter 4 and insulin receptor substrate-1 messenger RNA expression in omental and subcutaneous adipose tissue in women. 1937 84

Obesity is associated with an increased incidence of insulin resistance (IR), type 2 diabetes mellitus and cardiovascular diseases. The increased risk for cardiovascular diseases could partly be caused by a prothrombotic state that exists because of abdominal obesity. Adipose tissue induces thrombocyte activation by the production of adipose tissue-derived hormones, often called adipokines, of which some such as leptin and adiponectin have been shown to directly interfere with platelet function. Increased adipose tissue mass induces IR and systemic low-grade inflammation, also affecting platelet function. It has been demonstrated that adipose tissue directly impairs fibrinolysis by the production of plasminogen activator inhibitor-1 and possibly thrombin-activatable fibrinolysis inhibitor. Adipose tissue may contribute to enhanced coagulation by direct tissue factor production, but hypercoagulability is likely to be primarily caused by affecting hepatic synthesis of the coagulation factors fibrinogen, factor VII, factor VIII and tissue factor, by releasing free fatty acids and pro-inflammatory cytokines (tumour necrosis factor-alpha, interleukin-1beta and interleukin-6) into the portal circulation and by inducing hepatic IR. Adipose tissue dysfunction could thus play a causal role in the prothrombotic state observed in obesity, by directly and indirectly affecting haemostasis, coagulation and fibrinolysis.
 ...
PMID:Role of adipose tissue in haemostasis, coagulation and fibrinolysis. 1946 Jan 18

Postprandial metabolic dysregulation plays a role in the development of atherosclerosis. Visceral fat accumulation is an important component of various metabolic disorders including glucose intolerance, dyslipidemia, and hypertension, which correlate with atherosclerotic cardiovascular disease. The aim of the present study was to compare the postprandial response of various metabolic parameters, blood pressure, adiponectin, and oxidative stress to 75-g oral glucose tolerance test (OGTT) in men with (n = 23) and without (n = 7) abdominal obesity based on waist circumference (WC) cutoff value of 85 cm (based on the Japanese criteria for the metabolic syndrome). The cross-sectional prospective study included 30 male subjects who were on no medications and newly diagnosed with mild hypertension and/or dyslipidemia. The percentage change in each parameter ([each parameter at 120 minutes after an OGTT - that before an OGTT]/that before an OGTT x 100) was calculated. The percentage systolic blood pressure, percentage diastolic blood pressure, and percentage triglyceride were -6.3% +/- 3.5%, -9.4% +/- 3.0%, and -10.2% +/- 2.1%, respectively, in the WC less than 85 group (vs baseline: P = .10, P < .01, and P < .001) and 2.0% +/- 1.7%, 0.9% +/- 2.4%, and 2.8% +/- 3.3%, respectively, in the WC at least 85 group (vs WC <85 group: P < .05, each). However, there were no significant differences in percentage total cholesterol and percentage high-density lipoprotein cholesterol between the 2 groups. The percentage thiobarbituric acid-reacting substances tended to be lower in the WC less than 85 group (vs baseline: P = .07), but not in the WC at least 85 group, albeit statistically insignificant (WC <85 vs >/=85 group: P = .057). The maximum carotid intima-media thickness was larger in the WC at least 85 group than the WC less than 85 group (P < .05). Evaluation of postprandial changes in obesity-related parameters may be important in preventing atherosclerotic diseases.
 ...
PMID:Dysregulation of glucose, insulin, triglyceride, blood pressure, and oxidative stress after an oral glucose tolerance test in men with abdominal obesity. 1985 Mar 10


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>