Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex

Abstract

Aims/hypothesis. Increased intra-abdominal fat is associated with insulin resistance and an atherogenic lipoprotein profile. Circulating concentrations of adiponectin, an adipocyte-derived protein, are decreased with insulin resistance. We investigated the relationships between adiponectin and leptin, body fat distribution, insulin sensitivity and lipoproteins. Methods. We measured plasma adiponectin, leptin and lipid concentrations, intra-abdominal and subcutaneous fat areas by CT scan, and insulin sensitivity index (S I ) in 182 subjects (76 M/106F). Results. Adiponectin concentrations were higher in women than in men (7.4±2.9 vs 5.4±2.3 µg/ml, p<0.0001) as were leptin concentrations (19.1±13.7 vs 6.9±5.1 ng/ml, p<0.0001). Women were more insulin sensitive (S I : 6.8±3.9 vs 5.9±4.4×10 −5 min −1 /(pmol/l), p<0.01) and had more subcutaneous (240±133 vs 187±90 cm 2 , p<0.01), but less intra-abdominal fat (82±57 vs 124±68 cm 2 , p<0.0001). By simple regression, adiponectin was positively correlated with age (r=0.227, p<0.01) and S I (r=0.375, p<0.0001), and negatively correlated with BMI (r=−0.333, p<0.0001), subcutaneous (r=−0.168, p<0.05) and intra-abdominal fat (r=−0.35, p<0.0001). Adiponectin was negatively correlated with triglycerides (r=−0.281, p<0.001) and positively correlated with HDL cholesterol (r=0.605, p<0.0001) and Rf, a measure of LDL particle buoyancy (r=0.474, p<0.0001). By multiple regression analysis, adiponectin was related to age (p<0.0001), sex (p<0.005) and intra-abdominal fat (p<0.01). S I was related to intraabdominal fat (p<0.0001) and adiponectin (p<0.0005). Both intra-abdominal fat and adiponectin contributed independently to triglycerides, HDL cholesterol and Rf. Conclusion/interpretation. These data suggest that adiponectin concentrations are determined by intra-abdominal fat mass, with additional independent effects of age and sex. Adiponectin could link intra-abdominal fat with insulin resistance and an atherogenic lipoprotein profile. [Diabetologia (2003) 46:459-469] Keywords Adiponectin, Acrp30, adipoQ, central obesity, subcutaneous fat, intra-abdominal fat, insulin sensitivity, lipids, hepatic lipase, cardiovascular disease, leptin. It is well recognized that obesity and insulin resistance are closely related [1,2,3,4]. Android body fat distribution is associated with insulin resistance more than is a gynoid body fat distribution [5], with the site of abdominal fat distribution being an additional determinant of insulin sensitivity [6,7,8,9,10,11]. We found in both lean and obese subjects that the intraabdominal fat (IAF) depot is a stronger determinant of insulin sensitivity than the subcutaneous fat (SCF) depot [11], while SCF is the main determinant of the plasma concentration of leptin [11], an adipocyte-derived hormone regulating energy metabolism [12,13].

Beneficial effects of long-chain n-3 fatty acids included in an energy-restricted diet on insulin resistance in overweight and obese European young adults

“…Cross-sectional studies have shown adiponectin levels to be associated with insulin sensitivity [41,42]. When we use our baseline data to calculate correlations between insulin sensitivity and adiponectin (results not shown), we see the same associations as in the aforementioned cross-sectional studies.…”

Adiponectin complexes in human cerebrospinal fluid: distinct complex distribution from serum

“…Sexual dimorphism in terms of total systemic adiponectin, with women having higher levels of adiponectin than men, has been reported [10,42,43]. Although this was preserved in CSF [18], such findings were achieved using assay-based measures.…”

Associations of adiponectin with metabolic and vascular risk parameters in the British Regional Heart Study reveal stronger links to insulin resistance-related than to coronory heart disease risk-related parameters

“…2,24 The strongest associations, however, were seen between adiponectin and triglycerides and HDL-cholesterol (components of the insulin resistance syndrome) and these relationships were independent of adiposity and insulin resistance as has been reported in other studies. [26][27][28]43 The mechanisms by which adiponectin may affect blood lipids are substantially unknown. There is some evidence that such effects may be mediated via reduced hepatic lipase activity, an enzyme which contributes to a lowering of HDL-C concentrations 26 low adiponectin is associated with increased hepatic lipase activity in vivo independent of insulin resistance.…”

“…[26][27][28]43 The mechanisms by which adiponectin may affect blood lipids are substantially unknown. There is some evidence that such effects may be mediated via reduced hepatic lipase activity, an enzyme which contributes to a lowering of HDL-C concentrations 26 low adiponectin is associated with increased hepatic lipase activity in vivo independent of insulin resistance. 44 No association was seen between adiponectin and blood pressure, consistent with other population based studies.…”

“…2,24 In population-based studies, adiponectin is inversely associated with body mass index (BMI), insulin resistance, triglycerides, and positively associated with high-density lipoprotein (HDL)-cholesterol, components of the metabolic syndrome. [25][26][27][28][29] Although adiponectin has been associated with markers of inflammation in particular, C-reactive protein (CRP) 30,31 associations with other proinflammatory cytokines such as interleukin 6 (IL-6) however have been less consistent 31 and based on small selected populations. Moreover, whether the potential anti-inflammatory properties of adiponectin are mediated by its effect on insulin resistance remains unknown.…”