Changes of Adiponectin Oligomer Composition by Moderate Weight Reduction

Abstract

Adiponectin affects lipid metabolism and insulin sensitivity. However, adiponectin circulates in three different oligomers that may also have distinct biological functions. We aimed to analyze the role of these oligomers in obesity and lipid metabolism after weight reduction. A total of 17 obese volunteers (15 women and 2 men) participated in a weight reduction program. Individuals were characterized before and after 6 months of a balanced diet. Adiponectin was determined by enzyme-linked immunosorbent assay, and oligomers were detected by nondenaturating Western blot. BMI decreased (35.1 ؎ 1.2 to 32.8 ؎ 1.1 kg/m 2 , P < 0.001), which was associated with an improved metabolite profile. Total adiponectin increased from 5.3 ؎ 0.5 to 6.1 ؎ 0.6 g/ml (P ‫؍‬ 0.076). High (HMW) and medium molecular weight (MMW) adiponectin oligomers significantly increased during weight reduction (HMW: 0.37 ؎ 0.07 to 0.4 ؎ 0.08 g/ml, P ‫؍‬ 0.042; MMW: 2.3 ؎ 0.2 to 2.9 ؎ 0.3 g/ml, P ‫؍‬ 0.007), while low molecular weight (LMW) did not significantly change. Body weight inversely correlated with HMW (r ‫؍‬ ؊0.695, P ‫؍‬ 0.002) and positively with LMW (r ‫؍‬ 0.579, P ‫؍‬ 0.015). Interestingly, HDL cholesterol and HMW were strongly correlated (r ‫؍‬ 0.665, P ‫؍‬ 0.007). Indeed, HMW and free fatty acids before weight reduction predicted ϳ60% of HDL changes during intervention. In conclusion, weight reduction results in a relative increase of HMW/MMW adiponectin and a reduction of LMW adiponectin. Total adiponectin and especially HMW adiponectin are related to circulating HDL cholesterol. Diabetes 54: 2712-2719, 2005

Adiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism

“…Previous studies have shown that hypoadiponectinaemia is a hallmark of situations where insulin resistance occurs, including obesity, type 2 diabetes and gestational diabetes [12,[24][25][26]. Our longitudinal analysis in women from the pregravid state to the third trimester indicates that pregnancy in humans is a physiological situation in which circulating adiponectin is decreased, as is found in mice [11,27].…”

“…Both plasma adiponectin concentrations and mRNA levels were negatively correlated with fat mass (r=−0.50, p=0.005). The absolute amount of adiponectin multimers was quantified by non-denaturing gradient gel electrophoresis, which allows adequate separation of HMW and LMW complexes [16,24]. The primary forms of circulating adiponectin were a HMW oligomer of approximately 340 kDa, corresponding to a multimeric assembly of 12-16 molecules, and a LMW hexamer of approximately 160-180 kDa (Fig.…”

Blood glucose lowering by means of lifestyle intervention has different effects on adipokines as compared with insulin treatment in subjects with type 2 diabetes

“…However, in contrast to our findings an additional increase in the levels of adiponectin (2.7 μg/ml) was obtained. Recent studies have indicated that the most biological active form of adiponectin is the high and medium molecular weight adiponectin oligomers [43]. Our analysis does not quantify the content of the different forms of adiponectin and this may be the reason why we do not observe a significant interaction.…”

A disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerization

“…The plasma HMM form of adiponectin has also been shown to be suppressed by insulin and high levels of glucose (4). Conversely, the HMM adiponectin level is up-regulated by moderate weight reduction (10) or by treatment with thiazolidinediones (TZDs), which stimulate peroxisome proliferator activated receptor gamma (PPAR gamma) activity (8,11). However, the molecules that mediate these metabolic or pharmacological effects on adiponectin disulfide bond formation and multimerization remain unknown.…”