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

P. Luo, A. Dematteo, Z. Wang, L. Zhu, A. Wang, H. S. Kim, A. Pozzi, J. M. Stafford, J. M. Luther

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)901-910
Number of pages10
JournalDiabetologia
Volume56
Issue number4
DOIs
StatePublished - Apr 2013

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Aldosterone deficiency prevents high-fat-feeding-induced hyperglycaemia and adipocyte dysfunction in mice'. Together they form a unique fingerprint.

  • Cite this

    Luo, P., Dematteo, A., Wang, Z., Zhu, L., Wang, A., Kim, H. S., Pozzi, A., Stafford, J. M., & Luther, J. M. (2013). Aldosterone deficiency prevents high-fat-feeding-induced hyperglycaemia and adipocyte dysfunction in mice. Diabetologia, 56(4), 901-910. https://doi.org/10.1007/s00125-012-2814-8