Apelin treatment increases complete Fatty Acid oxidation, mitochondrial oxidative capacity, and biogenesis in muscle of insulin-resistant mice.

Camille Attané (1) , Camille Foussal (1) , Sophie Le Gonidec (1) , Alexandre Benani (2) , Danièle Daviaud (1) , Estelle Wanecq (1) , Rocío Guzmán-Ruiz (3) , Cédric Dray (1) , Veronic Bezaire (1) , Chloé Rancoule (1) , Keiji Kuba (4) , Mariano Ruiz-Gayo (1, 3) , Thierry Levade (1) , Josef Penninger (5) , Rémy Burcelin (1) , Luc Pénicaud (2) , Philippe Valet (1) , Isabelle Castan-Laurell (1)

1 I2MC - Institut des Maladies Métaboliques et Cardiovasculaires
2 CSGA - Centre des Sciences du Goût et de l'Alimentation [Dijon]
3 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
4 Dept Biol Informat & Expt Therapeut
5 Institute of Molecular Biotechnology

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.

Mots clés: AMP-Activated Protein Kinases; Animals; Cyclic AMP-Dependent Protein Kinases; High-Fat; Energy Metabolism; Fatty Acids; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Lipid Metabolism; Mice; Inbred C57BL; Skeletal; Oxidation-Reduction

Mots clés: Diet; Mitochondria; Muscle

Domaines: Sciences du Vivant [q-bio]; Alimentation et Nutrition

Camille Attané, Camille Foussal, Sophie Le Gonidec, Alexandre Benani, Danièle Daviaud, et al.. Apelin treatment increases complete Fatty Acid oxidation, mitochondrial oxidative capacity, and biogenesis in muscle of insulin-resistant mice.. Diabetes, 2012, 61 (2), pp.310-20. ⟨10.2337/db11-0100⟩. ⟨hal-00723095⟩