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

By Toshimasa Yamauchi, J. Kamon, H. Waki, Y. Imai, N. Shimozawa, K. Hioki, Shoko Uchida, Yusuke Ito, Kei Takakuwa, J. Matsui and 14 more. Journal of Biological Chemistry, 2003

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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 β-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 α. 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.

Subfields: Endocrine and Autonomic Systems, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/89cad1b9f3bac7ddbf893c0b2fc610596f93aa20

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Citations in the corpus

Molecular mediators of hepatic steatosis and liver injury. (2004, neutral): “79, 84).”
Metabolic Syndrome: Updates on Pathophysiology and Management in 2021 (2022, background): “In contrast, adiponectin’s effects counter those of leptin as it was established as an anti-atherogenic, anti-inflammatory, and anti-diabetic adipokine [42,43].”
Adiponectin: more than just another fat cell hormone? (2003, background): “In a separate experiment by the same group (30), amelioration of insulin resistance, -cell degranulation, and diabetes occurred in globular adiponectin transgenic (gAd Tg) crossed with leptindeficient ob/ob mice.”
Adiponectin: A novel adipokine linking adipocytes and vascular function. (2004, positive): “Adiponectin associated with foam cells in the fatty streak lesions, suppressed the expression of vascular cell adhesion mole- cule-1 (VCAM-1) and class A scavenger receptors, and tended to reduce levels of TNF␣ (31).”
Adiponectin: mechanistic insights and clinical implications (2012, background): “Bearing this important limitation in mind, globular adiponectin appears to act, at least in part, through AMPK (and, subsequently, by inhibiting acetyl-CoA carboxylase) [39, 40, 42] and PPARα [11, 43] to exert its metabolic effects in muscle.”
The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. (2003, positive): “In line with a recent study (44), infusion of adiponectin into obese ob/ob mice increased glucose tolerance as well as insulin sensitivity (Figure 8, a and b).”