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A combined transcriptomics and lipidomics analysis of subcutaneous, epididymal and mesenteric adipose tissue reveals marked functional differences

Author: Caesar, R. · Manieri, M. · Kelder, T. · Boekschoten, M. · Evelo, C. · Müller, M. · Kooistra, T. · Cinti, S. · Kleemann, R. · Drevon, C.A.
Type:article
Date:2010
Institution: TNO Kwaliteit van Leven
Source:PLoS ONE, 7, 5, 1-14
Identifier: 409283
Keywords: Biology · Biomedical Research · Acetyl coenzyme A · Adenosine triphosphate citrate lyase · Androgen receptor · Carbohydrate responsive element binding protein · Fatty acid synthase · Linoleic acid · Linolenic acid · Monounsaturated fatty acid · Omega 3 fatty acid · Omega 6 fatty acid · Transcription factor · Unclassified drug · Abdominal fat · Adipocyte · Animal cell · Animal tissue · Controlled study · Down regulation · Epididymis fat · Fat intake · Fatty acid desaturation · Fatty acid synthesis · Gene expression regulation · Lipid diet · Lipid metabolism · Lipid storage · Lipidomics · Lipogenesis · Male · Microarray analysis · Mouse · Nonhuman · Spermatogenesis · Subcutaneous fat · Transcriptomics

Abstract

Depot-dependent differences in adipose tissue physiology may reflect specialized functions and local interactions between adipocytes and surrounding tissues. We combined time-resolved microarray analyses of mesenteric- (MWAT), subcutaneous- (SWAT) and epididymal adipose tissue (EWAT) during high-fat feeding of male transgenic ApoE3Leiden mice with histology, targeted lipidomics and biochemical analyses of metabolic pathways to identify differentially regulated processes and site-specific functions. EWAT was found to exhibit physiological zonation. De novo lipogenesis in fat proximal to epididymis was stably low, whereas de novo lipogenesis distal to epididymis and at other locations was down-regulated in response to high-fat diet. The contents of linoleic acid and a-linolenic acid in EWAT were increased compared to other depots. Expression of the androgen receptor (Ar) was higher in EWAT than in MWAT and SWAT. We suggest that Ar may mediate depot-dependent differences in de novo lipogenesis rate and propose that accumulation of linoleic acid and alinolenic acid in EWAT is favored by testosterone-mediated inhibition of de novo lipogenesis and may promote further elongation and desaturation of these polyunsaturated fatty acids during spermatogenesis. © 2010 Caesar et al.