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

Luo P, Dematteo A, Wang Z, Zhu L, Wang A, Kim HS, Pozzi A, Stafford JM, Luther JM
Diabetologia. 2013 56 (4): 901-10

PMID: 23314847 · PMCID: PMC3593801 · DOI:10.1007/s00125-012-2814-8

AIMS/HYPOTHESIS - 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.

METHODS - 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.

RESULTS - 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.

CONCLUSIONS/INTERPRETATION - 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.

MeSH Terms (20)

Adipocytes Adiponectin Adipose Tissue Aldosterone Animals Blood Glucose Body Composition Constriction, Pathologic Diet, High-Fat Glucose Clamp Technique Hyperglycemia Insulin Insulin Resistance Liver Macrophages Male Mice Mice, Inbred C57BL Random Allocation Somatostatin

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