title: Tissue-specific regulation of sirtuin and nicotinamide adenine dinucleotide biosynthetic pathways identified in C57Bl/6 mice in response to high-fat feeding.
abstract: The sirtuin (SIRT)/nicotinamide adenine dinucleotide (NAD) system is implicated in development of type 2 diabetes (T2D) and diet-induced obesity, a major risk factor for T2D. Mechanistic links have not yet been defined. SIRT/NAD system gene expression and NAD/NADH levels were measured in liver, white adipose tissue (WAT) and skeletal muscle from mice fed either a low-fat diet or high-fat diet (HFD) for 3 days up to 16 weeks. An in-house custom-designed multiplex gene expression assay assessed all 7 mouse SIRTs (SIRT1-7) and 16 enzymes involved in conversion of tryptophan, niacin, nicotinamide riboside and metabolic precursors to NAD. Significantly altered transcription was correlated with body weight, fat mass, plasma lipids and hormones. Regulation of the SIRT/NAD system was associated with early (SIRT4, SIRT7, NAPRT1 and NMNAT2) and late phases (NMNAT3, NMRK2, ABCA1 and CD38) of glucose intolerance. TDO2 and NNMT were identified as markers of HFD consumption. Altered regulation of the SIRT/NAD system in response to HFD was prominent in liver compared with WAT or muscle. Multiple components of the SIRTs and NAD biosynthetic enzymes network respond to consumption of dietary fat. Novel molecular targets identified above could direct strategies for dietary/therapeutic interventions to limit metabolic dysfunction and development of T2D.
authors: Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB21 9SB, Scotland. Electronic address: j.drew@abdn.ac.uk.
authors: Janice E
authors: JE
authors: Drew
authors: Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB21 9SB, Scotland.
authors: Andrew J
authors: AJ
authors: Farquharson
authors: Biomathematics and Statistics Scotland, Aberdeen AB21 9SB, Scotland.
authors: Graham W
authors: GW
authors: Horgan
authors: Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB21 9SB, Scotland.
authors: Lynda M
authors: LM
authors: Williams
mesh_terms: D052436:Adipose Tissue, White / Q000201:enzymology / Q000378:metabolism; D050154:Adiposity; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D015971:Gene Expression Regulation, Enzymologic; D018149:Glucose Intolerance / Q000097:blood / Q000209:etiology / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism; D009243:NAD / Q000096:biosynthesis; D050903:Nicotinamide N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D009928:Organ Specificity; D025341:Principal Component Analysis; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000235:genetics / Q000378:metabolism*; D015430:Weight Gain
chemical_list: D015415:Biomarkers; D024101:Mitochondrial Proteins; C539736:Sirt7 protein, mouse; D009243:NAD; D014366:Tryptophan Oxygenase; D050903:Nicotinamide N-Methyltransferase; C494407:Nnmt protein, mouse; C514813:SIRT4 protein, mouse; D037761:Sirtuins
keywords: Glucose intolerance; High-fat diet; Mouse; Nicotinamide adenine dinucleotide; Sirtuin