Activation of AMP-activated protein kinase (AMPK) inhibits fatty acid synthesis in bovine mammary epithelial cells.
Activation of AMP-activated protein kinase (AMPK), a heterotrimeric energy-sensing protein, decreases lipid synthesis in liver tissue of various species; however, little is known about the role of AMPK in the regulation of fatty acid synthesis in bovine mammary epithelial cells. Here we report the presence of AMPK mRNA in MAC-T bovine mammary epithelial cells and mammary gland. Treatment of MAC-T with an AMPK activator dramatically decreased de novo fatty acid synthesis by inactivating acetyl-CoA carboxylase-alpha. Activation of AMPK also modified the mRNA expression of several lipogenic genes including fatty acid synthase, glycerol-3-phosphate acyltransferase, and fatty acid binding protein-3. Additionally, decreases in energy availability or rises in intracellular Ca(2+) most likely activated AMPK in MAC-T. These data suggest the presence of LKB1 and Ca(2+)/calmodulin-dependent kinase kinase, two known AMPK kinases, in MAC-T. Identifying AMPK as a molecular target capable of modifying energy substrate utilization may result in the development of new technologies that increase milk production or modify milk composition during periods of increased energy demand.
McFadden
Joseph W
JW
Department of Dairy Science, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Corl
Benjamin A
BA
D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors / Q000235:genetics; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000235:genetics; D002417:Cattle; D002460:Cell Line; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D005227:Fatty Acids / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000235:genetics; D050155:Lipogenesis / Q000235:genetics*; D008321:Mammary Glands, Animal / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012265:Ribonucleotides / Q000494:pharmacology
D005227:Fatty Acids; D012333:RNA, Messenger; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D005992:Glycerol-3-Phosphate O-Acyltransferase; D017346:Protein Serine-Threonine Kinases; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; C031143:AICA ribonucleotide