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

Caesar R, Manieri M, Kelder T, Boekschoten M, Evelo C, Müller M, Kooistra T, Cinti S, Kleemann R, Drevon CA - PLoS ONE (2010)

Bottom Line: EWAT was found to exhibit physiological zonation.The contents of linoleic acid and alpha-linolenic acid in EWAT were increased compared to other depots.We suggest that Ar may mediate depot-dependent differences in de novo lipogenesis rate and propose that accumulation of linoleic acid and alpha-linolenic 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway. Robert.Caesar@wlab.gu.se

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 alpha-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 alpha-linolenic 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.

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Lipogenesis and expression of genes involved in lipogenesis in proximal epididymal adipose tissues compared to other adipose tissues during chow feeding.A) De novo lipogenesis determined by incorporation of [14C] from radiolabeled glucose in triacylglycerols in explants from the proximal and distal zone of epididymal (EWAT), subcutaneous (SWAT) and mesenteric (MWAT) adipose tissue. B) Expression of genes encoding fatty acid synthase (Fasn) and ATP citrate lyase (Acly) determined by RT-PCR. De novo lipogenesis and Fasn expression but not Acly expression differed between depots (p<0.05, Kruskall-Wallis analysis, 3 degrees of freedom). *Difference between proximal EWAT and other adipose tissues determined by Mann-Whitney analysis (p<0.05 adjusted to 0.017 by Bonferroni correction). Experiments were performed with 4–5 animals. Error bars indicate standard deviation. de novo lipogenesis: MWAT-EWAT proximal U(4,5) = 0, p = 0.014; SWAT-EWAT proximal U(5) = 5, p = 0.12; EWAT proximal-EWAT distal U(5) = 0, p = 0.009; Fasn: MWAT-EWAT proximal U(4) = 2, p = 0.08; SWAT-EWAT proximal U(4) = 0, 0.02; EWAT proximal-EWAT distal U(4) = 0, p = 0.02; Acly: MWAT-EWAT proximal U(4) = 2, p = 0.08; SWAT-EWAT proximal U(4) = 2, 0.08; EWAT proximal-EWAT distal U(4,3) = 5, p = 0.72.
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pone-0011525-g005: Lipogenesis and expression of genes involved in lipogenesis in proximal epididymal adipose tissues compared to other adipose tissues during chow feeding.A) De novo lipogenesis determined by incorporation of [14C] from radiolabeled glucose in triacylglycerols in explants from the proximal and distal zone of epididymal (EWAT), subcutaneous (SWAT) and mesenteric (MWAT) adipose tissue. B) Expression of genes encoding fatty acid synthase (Fasn) and ATP citrate lyase (Acly) determined by RT-PCR. De novo lipogenesis and Fasn expression but not Acly expression differed between depots (p<0.05, Kruskall-Wallis analysis, 3 degrees of freedom). *Difference between proximal EWAT and other adipose tissues determined by Mann-Whitney analysis (p<0.05 adjusted to 0.017 by Bonferroni correction). Experiments were performed with 4–5 animals. Error bars indicate standard deviation. de novo lipogenesis: MWAT-EWAT proximal U(4,5) = 0, p = 0.014; SWAT-EWAT proximal U(5) = 5, p = 0.12; EWAT proximal-EWAT distal U(5) = 0, p = 0.009; Fasn: MWAT-EWAT proximal U(4) = 2, p = 0.08; SWAT-EWAT proximal U(4) = 0, 0.02; EWAT proximal-EWAT distal U(4) = 0, p = 0.02; Acly: MWAT-EWAT proximal U(4) = 2, p = 0.08; SWAT-EWAT proximal U(4) = 2, 0.08; EWAT proximal-EWAT distal U(4,3) = 5, p = 0.72.

Mentions: Regulation of fatty acid metabolism differed between EWAT and the other adipose depots. We also observed that two EWAT samples at baseline exhibited high expression of de novo lipogenesis genes, whereas the expression levels for the two other samples were much lower (data not shown). To investigate if the observed variation is caused by regional differences within the EWAT depot, samples from the proximal and distal part of EWAT were analyzed. The proximal and distal regions comprised adipose tissue within 10 mm from epididymis and within 10 mm from the distal end of the EWAT depot, respectively (Figure 1). MWAT and SWAT samples were also included in the analyses. de novo lipogenesis was determined by measuring the transfer of [14C] from glucose to lipids in fresh adipose tissue explants. Strikingly, de novo lipogenesis in proximal EWAT was 70% lower compared to distal EWAT and SWAT, and 80% lower as compared to MWAT (Figure 5A). The low de novo lipogenesis activity in especially proximal EWAT was confirmed by gene expression analysis of fatty acid synthetase (Fasn) and ATP citrate lyase (Acly) (Figure 5B).


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

Caesar R, Manieri M, Kelder T, Boekschoten M, Evelo C, Müller M, Kooistra T, Cinti S, Kleemann R, Drevon CA - PLoS ONE (2010)

Lipogenesis and expression of genes involved in lipogenesis in proximal epididymal adipose tissues compared to other adipose tissues during chow feeding.A) De novo lipogenesis determined by incorporation of [14C] from radiolabeled glucose in triacylglycerols in explants from the proximal and distal zone of epididymal (EWAT), subcutaneous (SWAT) and mesenteric (MWAT) adipose tissue. B) Expression of genes encoding fatty acid synthase (Fasn) and ATP citrate lyase (Acly) determined by RT-PCR. De novo lipogenesis and Fasn expression but not Acly expression differed between depots (p<0.05, Kruskall-Wallis analysis, 3 degrees of freedom). *Difference between proximal EWAT and other adipose tissues determined by Mann-Whitney analysis (p<0.05 adjusted to 0.017 by Bonferroni correction). Experiments were performed with 4–5 animals. Error bars indicate standard deviation. de novo lipogenesis: MWAT-EWAT proximal U(4,5) = 0, p = 0.014; SWAT-EWAT proximal U(5) = 5, p = 0.12; EWAT proximal-EWAT distal U(5) = 0, p = 0.009; Fasn: MWAT-EWAT proximal U(4) = 2, p = 0.08; SWAT-EWAT proximal U(4) = 0, 0.02; EWAT proximal-EWAT distal U(4) = 0, p = 0.02; Acly: MWAT-EWAT proximal U(4) = 2, p = 0.08; SWAT-EWAT proximal U(4) = 2, 0.08; EWAT proximal-EWAT distal U(4,3) = 5, p = 0.72.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2902507&req=5

pone-0011525-g005: Lipogenesis and expression of genes involved in lipogenesis in proximal epididymal adipose tissues compared to other adipose tissues during chow feeding.A) De novo lipogenesis determined by incorporation of [14C] from radiolabeled glucose in triacylglycerols in explants from the proximal and distal zone of epididymal (EWAT), subcutaneous (SWAT) and mesenteric (MWAT) adipose tissue. B) Expression of genes encoding fatty acid synthase (Fasn) and ATP citrate lyase (Acly) determined by RT-PCR. De novo lipogenesis and Fasn expression but not Acly expression differed between depots (p<0.05, Kruskall-Wallis analysis, 3 degrees of freedom). *Difference between proximal EWAT and other adipose tissues determined by Mann-Whitney analysis (p<0.05 adjusted to 0.017 by Bonferroni correction). Experiments were performed with 4–5 animals. Error bars indicate standard deviation. de novo lipogenesis: MWAT-EWAT proximal U(4,5) = 0, p = 0.014; SWAT-EWAT proximal U(5) = 5, p = 0.12; EWAT proximal-EWAT distal U(5) = 0, p = 0.009; Fasn: MWAT-EWAT proximal U(4) = 2, p = 0.08; SWAT-EWAT proximal U(4) = 0, 0.02; EWAT proximal-EWAT distal U(4) = 0, p = 0.02; Acly: MWAT-EWAT proximal U(4) = 2, p = 0.08; SWAT-EWAT proximal U(4) = 2, 0.08; EWAT proximal-EWAT distal U(4,3) = 5, p = 0.72.
Mentions: Regulation of fatty acid metabolism differed between EWAT and the other adipose depots. We also observed that two EWAT samples at baseline exhibited high expression of de novo lipogenesis genes, whereas the expression levels for the two other samples were much lower (data not shown). To investigate if the observed variation is caused by regional differences within the EWAT depot, samples from the proximal and distal part of EWAT were analyzed. The proximal and distal regions comprised adipose tissue within 10 mm from epididymis and within 10 mm from the distal end of the EWAT depot, respectively (Figure 1). MWAT and SWAT samples were also included in the analyses. de novo lipogenesis was determined by measuring the transfer of [14C] from glucose to lipids in fresh adipose tissue explants. Strikingly, de novo lipogenesis in proximal EWAT was 70% lower compared to distal EWAT and SWAT, and 80% lower as compared to MWAT (Figure 5A). The low de novo lipogenesis activity in especially proximal EWAT was confirmed by gene expression analysis of fatty acid synthetase (Fasn) and ATP citrate lyase (Acly) (Figure 5B).

Bottom Line: EWAT was found to exhibit physiological zonation.The contents of linoleic acid and alpha-linolenic acid in EWAT were increased compared to other depots.We suggest that Ar may mediate depot-dependent differences in de novo lipogenesis rate and propose that accumulation of linoleic acid and alpha-linolenic 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway. Robert.Caesar@wlab.gu.se

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 alpha-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 alpha-linolenic 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.

Show MeSH