Apelin treatment increases complete Fatty Acid oxidation, mitochondrial oxidative capacity, and biogenesis in muscle of insulin-resistant mice.
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.
INSERM U1048, Toulouse, France.
Camille
C
Attané
Camille
C
Foussal
Sophie
S
Le Gonidec
Alexandre
A
Benani
Danièle
D
Daviaud
Estelle
E
Wanecq
Rocío
R
Guzmán-Ruiz
Cédric
C
Dray
Veronic
V
Bezaire
Chloé
C
Rancoule
Keiji
K
Kuba
Mariano
M
Ruiz-Gayo
Thierry
T
Levade
Josef
J
Penninger
Rémy
R
Burcelin
Luc
L
Pénicaud
Philippe
P
Valet
Isabelle
I
Castan-Laurell
D055372:AMP-Activated Protein Kinases / Q000502:physiology; D054392:Adipokines; D000818:Animals; D000073861:Apelin; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism*; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction
D054392:Adipokines; D000073861:Apelin; C402826:Apln protein, mouse; D005227:Fatty Acids; D036341:Intercellular Signaling Peptides and Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D055372:AMP-Activated Protein Kinases