title: Aging-associated reductions in lipolytic and mitochondrial proteins in mouse adipose tissue are not rescued by metformin treatment.
abstract: Mitochondrial enzyme expression is reduced in adipose tissue from old mice, yet little is known regarding mechanisms that could be mediating, or interventions that could be used, to reverse these changes. The purpose of this study was to examine the relationship between lipolytic and fatty acid reesterification enzymes, 5' adenosine monophosphate-activated protein kinase and mitochondrial proteins in adipose tissue from young versus old mice. A second aim was to determine whether metformin treatment could rescue the age-associated decline in adipose tissue mitochondrial proteins. Approximately 22-month-old male C57BL/6 mice were fed a diet with or without 0.5% metformin for 8 weeks. Compared with young mice (~11 wk of age), the protein content/phosphorylation of hormone-sensitive lipase, adipose tissue triglyceride lipase, and phosphoenolpyruvate carboxykinase were reduced in old mice. This was paralleled by increases in the plasma nonesterified fatty acid:glycerol ratio and reductions in adipose tissue 5' adenosine monophosphate-activated protein kinase activity and select mitochondrial proteins in old mice. There were no differences in these variables when comparing adipose tissue from young and 6-month-old mice. While metformin improved glucose homeostasis, it did not increase 5' adenosine monophosphate-activated protein kinase phosphorylation or mitochondrial enzymes. Our findings demonstrate a co-ordinated down regulation of lipolytic, reesterification, and mitochondrial enzymes in adipose tissue with aging that is unresponsive to metformin treatment.
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Ontario, Canada.
authors.forename: Elise
authors.initials: E
authors.lastname: Mennes
authors.affiliation: Department of Exercise and Nutrition Sciences, University at Buffalo, The State University of New York.
authors.forename: Cory M
authors.initials: CM
authors.lastname: Dungan
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Ontario, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Frendo-Cumbo
authors.affiliation: Department of Exercise and Nutrition Sciences, University at Buffalo, The State University of New York.
authors.forename: David L
authors.initials: DL
authors.lastname: Williamson
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Ontario, Canada.
authors.forename: David C
authors.initials: DC
authors.lastname: Wright
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000032:analysis; D000249:Adenosine Monophosphate / Q000502:physiology; D000273:Adipose Tissue / Q000737:chemistry* / Q000201:enzymology; D000375:Aging / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D015536:Down-Regulation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000097:blood; D006706:Homeostasis / Q000502:physiology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008049:Lipase / Q000032:analysis; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D024101:Mitochondrial Proteins / Q000032:analysis*; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000032:analysis; D011494:Protein Kinases / Q000032:analysis; D011506:Proteins / Q000032:analysis; D002787:Sterol Esterase / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis
chemical_list: D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D024101:Mitochondrial Proteins; D011506:Proteins; D000249:Adenosine Monophosphate; D008687:Metformin; D011494:Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D002787:Sterol Esterase; D008049:Lipase; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D005947:Glucose; D005990:Glycerol
keywords: AMPK.; Adipose; Lipolysis; Metformin; Mitochondria