Globular Adiponectin Protected ob/ob Mice from Diabetes and ApoE-deficient Mice from Atherosclerosis

Abstract

The adipocyte-derived hormone adiponectin has been shown to play important roles in the regulation of energy homeostasis and insulin sensitivity. In this study, we analyzed globular domain adiponectin (gAd) transgenic (Tg) mice crossed with leptin-deficient ob/ob or apoE-deficient mice. Interestingly, despite an unexpected similar body weight, gAd Tg ob/ob mice showed amelioration of insulin resistance and ␤-cell degranulation as well as diabetes, indicating that globular adiponectin and leptin appeared to have both distinct and overlapping functions. Amelioration of diabetes and insulin resistance was associated with increased expression of molecules involved in fatty acid oxidation such as acyl-CoA oxidase, and molecules involved in energy dissipation such as uncoupling proteins 2 and 3 and increased fatty acid oxidation in skeletal muscle of gAd Tg ob/ob mice. Moreover, despite similar plasma glucose and lipid levels on an apoE-deficient background, gAd Tg apoE-deficient mice showed amelioration of atherosclerosis, which was associated with decreased expression of class A scavenger receptor and tumor necrosis factor ␣. This is the first demonstration that globular adiponectin can protect against atherosclerosis in vivo.In conclusion, replenishment of globular adiponectin may provide a novel treatment modality for both type 2 diabetes and atherosclerosis.

Importance of adiponectin activity in the pathogenesis of Alzheimer's disease

“…1),4 it is reasonable to speculate that ‘loss of function’ of APN might promote metabolic diseases and that restoration of APN signaling might be beneficial. Consistent with this idea, it has been shown that stimulation of APN signaling by recombinant APN or an APN receptor agonist is effective in the treatment of a mouse model of metabolic disorders 5, 6…”

Globular adiponectin increases GLUT4 translocation and glucose uptake but reduces glycogen synthesis in rat skeletal muscle cells

“…A cleaved fragment containing the globular head group of adiponectin (gAd) has also been found circulating in human plasma [9], and the physiological importance of this fragment has been highlighted by recent studies reporting the correction of diabetes and insulin resistance in transgenic ob/ob mice expressing gAd [7]. Each of the circulating forms of adiponectin appears to mediate distinct, often tissue-specific, metabolic effects.…”

“…Injection of adiponectin into rodents has been shown to decrease resting blood glucose levels and protect animals with dietinduced obesity from developing insulin resistance [6][7][8][9]. Treatment of isolated skeletal muscle or C 2 C 12 myocytes with adiponectin stimulates glucose transport [6,10,11], suggesting that this may be one mechanism by which adiponectin acts to alleviate hyperglycaemia.…”

Effects of adiponectin on breast cancer cell growth and signaling

“…For example, decreased plasma Acrp30 levels are associated with certain insulin resistant states such as type 2 diabetes and coronary artery disease (Kadowaki and Yamauchi, 2005). Furthermore, specific factors associated with protection for some disease states such as decreased levels of triglycerides, increased insulin sensitivity, and increased high-density lipoprotein cholesterol levels are associated with increasing levels of plasma Acrp30 (Yamauchi et al, 2003b;Oh et al, 2007) Additionally general anti-inflammatory and anti-vascular effects are associated with high Acrp30 levels (Hopkins et al, 2007;Ouchi and Walsh, 2007). As has previously been shown for other adipokines, Acrp30 appears to have global effects on a number of different aspects of physiology and cell growth.…”