Aldosterone deficiency prevents high-fat-feeding-induced hyperglycaemia and adipocyte dysfunction in mice

作者：Luo P; Dematteo A; Wang Z; Zhu L; Wang A; Kim H S; Pozzi A; Stafford J M; Luther J M^*

来源：Diabetologia, 2013, 56(4): 901-910.

DOI：10.1007/s00125-012-2814-8

• Adiponectin
• Aldosterone
• Aldosterone synthase
• Diabetes
• Fatty liver
• Insulin
• Insulin resistance
• Insulin secretion
• Renin-angiotensin-aldosterone system

Obesity is associated with aldosterone excess, hypertension and the metabolic syndrome, but the relative contribution of aldosterone to obesity-related complications is debated. We previously demonstrated that aldosterone impairs insulin secretion, and that genetic aldosterone deficiency increases glucose-stimulated insulin secretion in vivo. We hypothesised that elimination of endogenous aldosterone would prevent obesity-induced insulin resistance and hyperglycaemia.
Wild-type and aldosterone synthase-deficient (As (-/-)) mice were fed a high-fat (HF) or normal chow diet for 12 weeks. We assessed insulin sensitivity and insulin secretion using clamp methodology and circulating plasma adipokines, and examined adipose tissue via histology.
HF diet induced weight gain similarly in the two groups, but As (-/-) mice were protected from blood glucose elevation. HF diet impaired insulin sensitivity similarly in As (-/-) and wild-type mice, assessed by hyperinsulinaemic-euglycaemic clamps. Fasting and glucose-stimulated insulin were higher in HF-fed As (-/-) mice than in wild-type controls. Although there was no difference in insulin sensitivity during HF feeding in As (-/-) mice compared with wild-type controls, fat mass, adipocyte size and adiponectin increased, while adipose macrophage infiltration decreased. HF feeding significantly increased hepatic steatosis and triacylglycerol content in wild-type mice, which was attenuated in aldosterone-deficient mice.
These studies demonstrate that obesity induces insulin resistance independently of aldosterone and adipose tissue inflammation, and suggest a novel role for aldosterone in promoting obesity-induced beta cell dysfunction, hepatic steatosis and adipose tissue inflammation.

• 出版日期2013-4