title: Insight into the impact of dietary saturated fat on tissue-specific cellular processes underlying obesity-related diseases.
abstract: This study investigated the influence of three high-fat diets (HFDs), differing in the percentage of total calories from saturated fat (SF) (6%, 12%, 24%) but identical in total fat (40%), for a 16-week period in mice on a variety of tissue-specific cellular processes believed to be at the root of obesity-related diseases. Specifically, we examined ectopic lipid accumulation, oxidative capacity [peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) mRNA and protein; mtDNA; Cox IV and cytochrome C protein; citrate synthase activity; and gene expression of fission 1, mitofusin (Mfn) 1 and Mfn2], oxidative stress (4-hydroxy-2-nonenal), endoplasmic reticulum (ER) stress (binding immunoglobulin protein, activating transcription factor 6-p50, p-eukaryotic initiation factor 2 alpha and x-box binding protein 1 spliced protein), inflammatory [p-c-Jun N-terminal kinase (JNK), p-nuclear factor kappa-B, p-p38 mitogen-activated protein kinase) and insulin signaling (p-Akt), and inflammation [tumor necrosis factor-alpha, monocyte chemotactic protein-1, interleukin-6, F4/80, toll-like receptor (TLR)2 and TLR4 gene expression] in various tissues, including the adipose tissue, liver, skeletal muscle and heart. In general, adipose and hepatic tissues were the only tissues which displayed evidence of dysfunction. All HFDs down-regulated adipose, cardiac and hepatic PGC-1α mRNA and hepatic citrate synthase activity, and induced adipose tissue oxidative stress, whereas only the 6%-SF and 12%-SF diet produced hepatic steatosis. However, compared to the 6%-SF and 24%-SF diets, consumption of the 12%-SF diet resulted in the greatest degree of dysregulation (hepatic ER and oxidative stress, JNK activation, increased F4/80 gene expression and down-regulation of adipose tissue Akt signaling). These findings suggest that the saturated fatty acid composition of an HFD can greatly influence the processes responsible for obesity-related diseases - nonalcoholic fatty liver disease, in particular - as well as provide further evidence that the mechanisms at the root of these diseases are diet and tissue sensitive.
authors.affiliation: Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, USA; Division of Applied Physiology, Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Reilly T
authors.initials: RT
authors.lastname: Enos
authors.affiliation: Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, USA.
authors.forename: Kandy T
authors.initials: KT
authors.lastname: Velázquez
authors.affiliation: Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, USA. Electronic address: Angela.Murphy@uscmed.sc.edu.
authors.forename: E Angela
authors.initials: EA
authors.lastname: Murphy
mesh_terms: D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050154:Adiposity; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D059865:Endoplasmic Reticulum Stress; D005786:Gene Expression Regulation; D050356:Lipid Metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology; D009765:Obesity / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009928:Organ Specificity; D018384:Oxidative Stress; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D004041:Dietary Fats; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; C029310:lard
keywords: ER and oxidative stress; High-fat diet; Inflammatory and insulin signaling; Mitochondria; Saturated fat
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