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

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

Research output: Contribution to journalArticle

18 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Aldosterone
Adipocytes
Hyperglycemia
Cytochrome P-450 CYP11B2
Fats
Insulin Resistance
Obesity
Insulin
Adipose Tissue
High Fat Diet
Inflammation
Glucose
Adipokines
Glucose Clamp Technique
Adiponectin
Weight Gain
Blood Glucose
Hepatocytes
Fasting
Histology

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

Cite this

Aldosterone deficiency prevents high-fat-feeding-induced hyperglycaemia and adipocyte dysfunction in mice. / Luo, P.; Dematteo, A.; Wang, Z.; Zhu, Liang; Wang, A.; Kim, H. S.; Pozzi, A.; Stafford, J. M.; Luther, J. M.

In: Diabetologia, Vol. 56, No. 4, 04.2013, p. 901-910.

Research output: Contribution to journalArticle

Luo, P, Dematteo, A, Wang, Z, Zhu, L, Wang, A, Kim, HS, Pozzi, A, Stafford, JM & Luther, JM 2013, 'Aldosterone deficiency prevents high-fat-feeding-induced hyperglycaemia and adipocyte dysfunction in mice', Diabetologia, vol. 56, no. 4, pp. 901-910. https://doi.org/10.1007/s00125-012-2814-8
Luo, P. ; Dematteo, A. ; Wang, Z. ; Zhu, Liang ; Wang, A. ; Kim, H. S. ; Pozzi, A. ; Stafford, J. M. ; Luther, J. M. / Aldosterone deficiency prevents high-fat-feeding-induced hyperglycaemia and adipocyte dysfunction in mice. In: Diabetologia. 2013 ; Vol. 56, No. 4. pp. 901-910.
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AU - Wang, A.

AU - Kim, H. S.

AU - Pozzi, A.

AU - Stafford, J. M.

AU - Luther, J. M.

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