Effect of metformin and lipid emulsion on the circadian gene expression in muscle cells.
The circadian clock influences nearly all aspects of metabolism. However, little is known regarding the effect of the energy status on circadian rhythms. Our aim was to test the effect of two opposing energy situations, metformin and lipid emulsion (LE), on clock and metabolic circadian expression in differentiated C2C12 myotubes. Metformin treatment led to depleted ATP levels accompanied by elevated NADH levels, whereas LE treatment led to increased ATP and NAD(+) levels. Nevertheless, both LE and metformin treatments activated the AMP-activated protein kinase (AMPK) pathway. In contrast, the effect on circadian rhythms was completely different. LE led to disrupted clock and metabolic gene expression, whereas metformin led to mainly high-amplitude shifted rhythms. Combination of metformin and LE led to an antagonistic effect on circadian gene expression. Although metformin and LE have an opposing effect on circadian gene expression and on the cellular energy status, they both lead to AMPK activation.
Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel.
Maayan
M
Barnea
Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel.
Tamar
T
Cohen-Yogev
Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel.
Nava
N
Chapnik
Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel.
Zecharia
Z
Madar
Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel. Electronic address: oren.froy@mail.huji.ac.il.
Oren
O
Froy
D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics*; D004655:Emulsions / Q000008:administration & dosage; D004734:Energy Metabolism / Q000187:drug effects* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008055:Lipids / Q000008:administration & dosage; D008687:Metformin / Q000008:administration & dosage; D051379:Mice; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal
D004655:Emulsions; D008055:Lipids; D008687:Metformin; D055372:AMP-Activated Protein Kinases
C2C12 myotubes; Circadian rhythms; Lipid emulsion; Metabolism; Metformin