Extended multiplexing of tandem mass tags (TMT) labeling reveals age and high fat diet specific proteome changes in mouse epididymal adipose tissue

Deanna L. Plubell, Phillip Wilmarth, Yuqi Zhao, Alexandra M. Fenton, Jessica Minnier, Ashok P. Reddy, John Klimek, Xia Yang, Larry David, Nathalie Pamir

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The lack of high-throughput methods to analyze the adipose tissue protein composition limits our understanding of the protein networks responsible for age and diet related metabolic response. We have developed an approach using multiple-dimension liquid chromatography tandem mass spectrometry and extended multiplexing (24 biological samples) with tandem mass tags (TMT) labeling to analyze proteomes of epididymal adipose tissues isolated from mice fed either low or high fat diet for a short or a long-term, and from mice that aged on low versus high fat diets. The peripheral metabolic health (as measured by body weight, adiposity, plasma fasting glucose, insulin, triglycerides, total cholesterol levels, and glucose and insulin tolerance tests) deteriorated with diet and advancing age, with long-term high fat diet exposure being the worst. In response to short-term high fat diet, 43 proteins representing lipid metabolism (e.g. AACS, ACOX1, ACLY) and red-ox pathways (e.g. CPD2, CYP2E, SOD3) were significantly altered (FDR < 10%). Long-term high fat diet significantly altered 55 proteins associated with immune response (e.g. IGTB2, IFIT3, LGALS1) and rennin angiotensin system (e.g. ENPEP, CMA1, CPA3, AN-PEP). Age-related changes on low fat diet significantly altered only 18 proteins representing mainly urea cycle (e.g. OTC, ARG1, CPS1), and amino acid biosynthesis (e.g. GMT, AKR1C6). Surprisingly, high fat diet driven age-related changes culminated with alterations in 155 proteins involving primarily the urea cycle (e.g. ARG1, CPS1), immune response/complement activation (e.g. C 3, C4b, C 8, C9, CFB, CFH, FGA), extracellular remodeling (e.g. EFEMP1, FBN1, FBN2, LTBP4, FERMT2, ECM1, EMILIN2, ITIH3) and apoptosis (e.g. YAP1, HIP1, NDRG1, PRKCD, MUL1) pathways. Using our adipose tissue tailored approach we have identified both age-related and high fat diet specific proteomic signatures highlighting a pronounced involvement of arginine metabolism in response to advancing age, and branched chain amino acid metabolism in early response to high fat feeding. Data are available via ProteomeXchange with identifier PXD005953.

Original languageEnglish (US)
Pages (from-to)873-890
Number of pages18
JournalMolecular and Cellular Proteomics
Volume16
Issue number5
DOIs
StatePublished - May 1 2017

Fingerprint

High Fat Diet
Proteome
Nutrition
Multiplexing
Labeling
Adipose Tissue
Fats
Tissue
Fat-Restricted Diet
Proteins
Urea
Chymosin
Galectin 1
Insulin
Diet
Metabolism
Branched Chain Amino Acids
Complement Activation
Adiposity
Angiotensins

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

Cite this

Extended multiplexing of tandem mass tags (TMT) labeling reveals age and high fat diet specific proteome changes in mouse epididymal adipose tissue. / Plubell, Deanna L.; Wilmarth, Phillip; Zhao, Yuqi; Fenton, Alexandra M.; Minnier, Jessica; Reddy, Ashok P.; Klimek, John; Yang, Xia; David, Larry; Pamir, Nathalie.

In: Molecular and Cellular Proteomics, Vol. 16, No. 5, 01.05.2017, p. 873-890.

Research output: Contribution to journalArticle

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