Apelin treatment increases complete fatty acid oxidation, mitochondrial oxidative capacity, and biogenesis in muscle of insulin-resistant mice

Camille Attané, Camille Foussal, Sophie Le Gonidec, Alexandre Benani, Danièle Daviaud, Estelle Wanecq, Rocío Guzmán-Ruiz, Cédric Dray, Veronic Bezaire, Chloé Rancoule, Keiji Kuba, Mariano Ruiz-Gayo, Thierry Levade, Josef Penninger, Rémy Burcelin, Luc Pénicaud, Philippe Valet, Isabelle Castan-Laurell

Research output: Contribution to journalArticlepeer-review

165 Citations (Scopus)

Abstract

Both acute and chronic apelin treatment have been shown to improve insulin sensitivity in mice. However, the effects of apelin on fatty acid oxidation (FAO) during obesity-related insulin resistance have not yet been addressed. Thus, the aim of the current study was to determine the impact of chronic treatment on lipid use, especially in skeletal muscles. High-fat diet (HFD)- induced obese and insulin-resistant mice treated by an apelin injection (0.1 μmol/kg/day i.p.) during 4 weeks had decreased fat mass, glycemia, and plasma levels of triglycerides and were protected from hyperinsulinemia compared with HFD PBS-treated mice. Indirect calorimetry experiments showed that apelin-treated mice had a better use of lipids. The complete FAO, the oxidative capacity, and mitochondrial biogenesis were increased in soleus of apelin-treated mice. The action of apelin was AMP-activated protein kinase (AMPK) dependent since all the effects studied were abrogated in HFD apelin-treated mice with muscle-specific inactive AMPK. Finally, the apelin-stimulated improvement of oxidative capacity led to decreased levels of acylcarnitines and enhanced insulin-stimulated glucose uptake in soleus. Thus, by promoting complete lipid use in muscle of insulin-resistant mice through mitochondrial biogenesis and tighter matching between FAO and the tricarboxylic acid cycle, apelin treatment could contribute to insulin sensitivity improvement.

Original languageEnglish
Pages (from-to)310-320
Number of pages11
JournalDiabetes
Volume61
Issue number2
DOIs
Publication statusPublished - Feb 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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