title: Time course of high-fat diet-induced reductions in adipose tissue mitochondrial proteins: potential mechanisms and the relationship to glucose intolerance.
abstract: Increasing evidence suggests that reduced adipose tissue mitochondrial content is associated with the pathogenesis of type 2 diabetes. These investigations have utilized severely insulin-resistant rodent models. Thus, it is difficult to ascertain the potential mechanisms that initiate these changes and whether reductions in adipose mitochondria are an initiating event in the development of impaired glucose homeostasis. Thus, we sought to determine the time course of high-fat diet-induced reductions of mitochondrial content in epididymal adipose tissue in relation to changes in purported mediators of mitochondrial biogenesis and the development of impaired glucose homeostasis. Male Wistar rats were fed a high-fat diet ( approximately 59% of kcals from fat) for 2, 4, or 6 wk. Six weeks of high-fat feeding resulted in reductions in CORE I, COX IV, cytochrome c, HSP60, relative mtDNA copy number, and PGC-1alpha expression. These changes were not associated with decreases in eNOS and AMPK or increases in markers of oxidative stress. Interestingly, ex vivo treatment of adipose tissue cultures with palmitate led to decreases in PGC-1alpha expression and COX IV and CORE I protein content as observed in vivo. Thus, the high-fat diet-induced reductions in adipose tissue mitochondrial proteins may be mediated by increases in plasma fatty acids. Importantly, reductions in adipose tissue mitochondrial content occurred after the development of impaired glucose homeostasis. Thus, reductions in adipose tissue mitochondrial proteins are most likely not a causal event in the development of impaired glucose homeostasis.
authors.affiliation: Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Sutherland
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Capozzi
authors.forename: N Joan
authors.initials: NJ
authors.lastname: Turchinsky
authors.forename: Rhonda C
authors.initials: RC
authors.lastname: Bell
authors.forename: David C
authors.initials: DC
authors.lastname: Wright
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052436:Adipose Tissue, White / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000032:analysis; D004041:Dietary Fats / Q000008:administration & dosage*; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D018149:Glucose Intolerance / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019308:Palmitic Acid / Q000494:pharmacology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004272:DNA, Mitochondrial; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D019308:Palmitic Acid; D052250:Nitric Oxide Synthase Type III; D055372:AMP-Activated Protein Kinases