Apelin Treatment Increases Complete Fatty Acid Oxidation, Mitochondrial Oxidative Capacity, and Biogenesis in Muscle of Insulin-Resistant Mice
- Camille Attané1,2,
- Camille Foussal1,2,
- Sophie Le Gonidec1,2,
- Alexandre Benani3,
- Danièle Daviaud1,2,
- Estelle Wanecq1,2,
- Rocío Guzmán-Ruiz4,
- Cédric Dray1,2,
- Veronic Bezaire1,2,
- Chloé Rancoule1,2,
- Keiji Kuba5,
- Mariano Ruiz-Gayo4,
- Thierry Levade1,2,
- Josef Penninger6,
- Rémy Burcelin1,2,
- Luc Pénicaud3,
- Philippe Valet1,2 and
- Isabelle Castan-Laurell1,2⇓
- 1INSERM U1048, Toulouse, France
- 2Université de Toulouse, Université Paul Sabatier, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France
- 3Centre des Sciences du Goût et de l'Alimentation, Unité Mixte de Recherche 6265–Centre National de la Recherche Scientifique 13241–Institut National de la Recherche Agronomique, Université de Bourgogne, Dijon, France
- 4Departemento de Ciencias Farmacéuticas y de la Alimentación, School of Pharmacy, University CEU–San Pablo, Madrid, Spain
- 5Department of Biological Informatics and Experimental Therapeutics, Akita University Graduate School of Medicine, Akita, Japan
- 6Institute of Molecular Biotechnology, Vienna, Austria
- Corresponding author: Isabelle Castan-Laurell, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-0100/-/DC1.
- Received January 26, 2011.
- Accepted November 27, 2011.
- © 2012 by the American Diabetes Association.
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