Mechanisms regulating energy metabolism by adiponectin in obesity and diabetes

Abstract

Nutritional control of molecular events has become of great interest given the increased incidence of diet-induced obesity, and consequently Type 2 (non-insulin-dependent) diabetes, in recent years. The altered adipose tissue content in obese individuals results in an altered profile of circulating adipokines, and here we focus on adiponectin, whose circulating levels decrease in obese individuals. Adiponectin is a 30 kDa protein but circulates primarily as hexameric, oligomeric and, to a lesser extent, trimeric forms. Full-length adiponectin can also be cleaved to produce a fragment containing the globular domain that exerts potent metabolic effects. Adiponectin has insulin-mimetic and -sensitizing actions including stimulation of glucose uptake in skeletal muscle and suppression of glucose production in liver. Hence, adiponectin has attracted great interest as an antidiabetic agent. Adiponectin acts via two receptor isoforms, AdipoR1 (adiponectin receptor 1) and AdipoR2, which have distinct tissue distributions and affinities for recognition of the various adiponectin forms. Expression of AdipoR isoforms can be regulated by hyperinsulinaemia and hyperglycaemia with the consequence of increased sensitivity or resistance to specific forms of adiponectin. In summary, regulation of adiponectin or AdipoR expression may be of great importance in the development of metabolic perturbations characteristic of Type 2 diabetes in obese individuals.

Leptin prevents the metabolic effects of adiponectin in L6 myotubes

“…[9, H]Palmitic acid was measured as previously described [7,27]. Briefly, cells were washed and treated for 1 min with transport solution (140 mmol/l NaCl, 20 mmol/l HEPES-Na, 2.5 mmol/l MgSO 4 O produced in the incubation medium as described previously [28]. Medium was collected into Eppendorf tubes.…”

“…One potential underlying mechanism is altered endocrine effects of adipose-derived hormones [3]. Due to its anti-diabetic, anti-atherogenic, anti-inflammatory and cardioprotective functions [4,5], adiponectin has attracted great interest since being identified. The metabolic effects of adiponectin, both direct and via insulin sensitisation, have been identified in skeletal muscle and liver by several groups [6,7].…”

Systemic Adiponectin Malfunction as a Risk Factor for Cardiovascular Disease

“…receptor's relative contribution to Ad cardioprotective signaling remain ongoing. Receptor expression levels in skeletal muscle and adipose tissue correlate with insulin levels, and are reduced in diabetic mouse models (6,16). By Scatchard plot analysis, Yamuchi and colleagues have shown that AdipoR1 is a receptor with high affinity for globular Ad, whereas AdipoR2 is a receptor with intermediate affinity for both fulllength and globular Ad (70,75).…”

Inflammatory markers and metabolic syndrome among adolescents

“…38 Increased adiponectin is associated with a lower risk of impaired glucose tolerance, decreased myocardial infarction risk and has been proposed as a biomarker of early atherosclerosis. 8,9,39 Adiponectin decreases in obesity and related diseases, and may be involved in cardiovascular disease and type 2 diabetes mellitus pathology. 40 Hotta et al 41 showed that adiponectin levels in patients with type 2 diabetes mellitus were lower than those of non-diabetic patients, and were particularly low in subjects with coronary artery disease.…”