Tissue-specific regulation of sirtuin and nicotinamide adenine dinucleotide biosynthetic pathways identified in C57Bl/6 mice in response to high-fat feeding

Janice E. Drew, Andrew J. Farquharson, Graham W Horgan, Lynda M. Williams

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Abstract

The sirtuin/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. Sirtuin/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 (LFD) 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 sirtuins (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 sirtuin/NAD system was associated with early (SIRT4, SIRT7, NAPRT1, NMNAT2) and late phases (NMNAT3, NMRK2, ABCA1, 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 to WAT or muscle. Multiple components of the sirtuins 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.
Original languageEnglish
Pages (from-to)20-29
Number of pages10
JournalThe Journal of Nutritional Biochemistry
Volume37
Early online date14 Aug 2016
DOIs
Publication statusPublished - Nov 2016

Fingerprint

Biosynthetic Pathways
NAD
Fats
Tissue
Nutrition
High Fat Diet
Medical problems
Sirtuins
Type 2 Diabetes Mellitus
White Adipose Tissue
Gene expression
Liver
Muscle
Gene Expression
Fat-Restricted Diet
Glucose Intolerance
Niacin
Dietary Fats
Enzymes
Transcription

Keywords

  • glucose intolerance
  • high fat diet
  • nicotinamide adenine dinucleotide
  • mouse
  • sirtuin

Cite this

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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/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. Sirtuin/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 (LFD) 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 sirtuins (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 sirtuin/NAD system was associated with early (SIRT4, SIRT7, NAPRT1, NMNAT2) and late phases (NMNAT3, NMRK2, ABCA1, 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 to WAT or muscle. Multiple components of the sirtuins 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.",
keywords = "glucose intolerance, high fat diet, nicotinamide adenine dinucleotide, mouse, sirtuin",
author = "Drew, {Janice E.} and Farquharson, {Andrew J.} and Horgan, {Graham W} and Williams, {Lynda M.}",
note = "Funding: The Scottish Government's Rural and Environment Science and Analytical Services Division.",
year = "2016",
month = "11",
doi = "10.1016/j.jnutbio.2016.07.013",
language = "English",
volume = "37",
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journal = "The Journal of Nutritional Biochemistry",
issn = "0955-2863",
publisher = "Elsevier Inc.",

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T1 - Tissue-specific regulation of sirtuin and nicotinamide adenine dinucleotide biosynthetic pathways identified in C57Bl/6 mice in response to high-fat feeding

AU - Drew, Janice E.

AU - Farquharson, Andrew J.

AU - Horgan, Graham W

AU - Williams, Lynda M.

N1 - Funding: The Scottish Government's Rural and Environment Science and Analytical Services Division.

PY - 2016/11

Y1 - 2016/11

N2 - The sirtuin/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. Sirtuin/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 (LFD) 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 sirtuins (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 sirtuin/NAD system was associated with early (SIRT4, SIRT7, NAPRT1, NMNAT2) and late phases (NMNAT3, NMRK2, ABCA1, 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 to WAT or muscle. Multiple components of the sirtuins 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.

AB - The sirtuin/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. Sirtuin/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 (LFD) 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 sirtuins (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 sirtuin/NAD system was associated with early (SIRT4, SIRT7, NAPRT1, NMNAT2) and late phases (NMNAT3, NMRK2, ABCA1, 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 to WAT or muscle. Multiple components of the sirtuins 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.

KW - glucose intolerance

KW - high fat diet

KW - nicotinamide adenine dinucleotide

KW - mouse

KW - sirtuin

U2 - 10.1016/j.jnutbio.2016.07.013

DO - 10.1016/j.jnutbio.2016.07.013

M3 - Article

VL - 37

SP - 20

EP - 29

JO - The Journal of Nutritional Biochemistry

JF - The Journal of Nutritional Biochemistry

SN - 0955-2863

ER -