ABSTRACT
AMP-activated protein kinases (AMPK) are heterotrimeric, αßγ, serine/threonine kinases. The γ3-AMPK subunit is particularly interesting in muscle physiology because 1) it is specifically expressed in skeletal muscle, 2) α2ß2γ3 is the AMPK heterotrimer activated during exercise in humans, and 3) it is down-regulated in humans after a training period. However, mechanisms underlying this decrease of γ3-AMPK expression remained unknown. We investigated whether the expression of AMPK subunits and particularly that of γ3-AMPK are regulated by the PPARß pathway. We report that PPARß activation with GW0742 induces a rapid (2 h) and sustained down-regulation of γ3-AMPK expression both in mouse skeletal muscles and in culture myotubes. Concomitantly, phosphorylation levels of both AMPK and acetyl-coenzyme A carboxylase are rapidly modified. The γ3-AMPK down-regulation is also observed in muscles from young and adult transgenic mice with muscle-specific overexpression of peroxisome proliferator-activated receptor ß (PPARß). We showed that γ3-AMPK down-regulation is a rapid physiological muscle response observed in mouse after running exercise or fasting, two situations leading to PPARß activation. Finally, using C2C12, we demonstrated that dose and time-dependent down-regulation of γ3-AMPK expression upon GW0742 treatment, is due to decrease γ3-AMPK promoter activity.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Muscle, Skeletal/enzymology , PPAR-beta/metabolism , Protein Subunits/metabolism , AMP-Activated Protein Kinases/genetics , Animals , Down-Regulation/drug effects , Enzyme Activation/drug effects , Male , Mice , Mice, Inbred C57BL , Muscle Fibers, Skeletal/drug effects , Muscle Fibers, Skeletal/enzymology , Muscle, Skeletal/drug effects , PPAR-beta/genetics , Physical Conditioning, Animal , Promoter Regions, Genetic/genetics , Protein Subunits/genetics , Starvation/enzymology , Thiazoles/pharmacology , Transcription, Genetic/drug effectsABSTRACT
OBJECTIVE: To analyse the status of vitamin D and the influence of a supplement of vitamin D in neonates and infants during the first 6 months of life in the african equatorial environnement of Gabon. DESIGN: Clinical (weight, height, head circumference, and diseases) and biological (calcemia, phosphatemia, serum alkaline phosphatase activity and plasma 25-hydroxyvitamin D levels) parameters were compared between 2 groups of children: group 1: 41 infants receving a daily supplement of 1000 IU of vitamin D, and group 2: 38 infants without vitamin D supplement. RESULTS: No significant differences were observed between the 2 groups concerning clinical and biological parameters. In particular plasma levels of 25-hydroxyvitamin D were normal and similar in both groups. CONCLUSION: A vitamin D supplement appears to be useless in 0 to 6 months infants living in Gabon.