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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.

Show MeSH
Rate of lipogenesis and expression of putative regulatory factors.A) Gene expression levels of the androgen receptor (Ar) in proximal and distal epididymal (EWAT) adipose tissue, in mesenteric (MWAT), and in subcutaneous (SWAT) adipose tissue determined by RT-PCR. B) Expression of the gene encoding the androgen receptor (Ar) determined by RT-PCR plotted against rate of lipogenesis measured by incorporation of [14C]glucose in TAG in adipose tissue explants. C) Expression of carbohydrate responsive element binding protein (ChREBP), ATP citrate lyase (Acly) and fatty acid synthase (Fasn) on 12 weeks of high-fat diet determined by microarray analysis. The expression level at baseline was set to 1 for all genes. (A) Ar 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). MWAT-EWAT proximal U(5) = 0, p = 0.009; SWAT-EWAT proximal U(5) = 1, 0.02; EWAT proximal-EWAT distal U(5) = 3, p = 0.05 (B) the relation between lipogenesis and Ar expression was determined by Pearson correlation coefficient with one-sided significance calculated by Cronbach's Alpha, (C) *p<0.05 (one way ANOVA with Tukey post hoc analysis, 4 degrees of freedom. Error bars indicate standard deviation. SWAT: ChREBP F(4,21) = 10, p = 0.0001; Acly F(4,21) = 30.0, p = 2.0×10−8; Fasn F(4,21) = 8.8, p = 0.0002; MWAT: ChREBP F(4,18) = 8.6, p = 0.0004; Acly F(4,18) = 29.9, p = 9.9×10−8; Fasn F(4,18) = 5.3, p = 0.0.005; EWAT: ChREBP F(4,20) = 2.8, p = 0.055; Acly F(4,20) = 1.4, p = 0.25; Fasn F(4,20) = 0.82, p = 0.53.
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pone-0011525-g007: Rate of lipogenesis and expression of putative regulatory factors.A) Gene expression levels of the androgen receptor (Ar) in proximal and distal epididymal (EWAT) adipose tissue, in mesenteric (MWAT), and in subcutaneous (SWAT) adipose tissue determined by RT-PCR. B) Expression of the gene encoding the androgen receptor (Ar) determined by RT-PCR plotted against rate of lipogenesis measured by incorporation of [14C]glucose in TAG in adipose tissue explants. C) Expression of carbohydrate responsive element binding protein (ChREBP), ATP citrate lyase (Acly) and fatty acid synthase (Fasn) on 12 weeks of high-fat diet determined by microarray analysis. The expression level at baseline was set to 1 for all genes. (A) Ar 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). MWAT-EWAT proximal U(5) = 0, p = 0.009; SWAT-EWAT proximal U(5) = 1, 0.02; EWAT proximal-EWAT distal U(5) = 3, p = 0.05 (B) the relation between lipogenesis and Ar expression was determined by Pearson correlation coefficient with one-sided significance calculated by Cronbach's Alpha, (C) *p<0.05 (one way ANOVA with Tukey post hoc analysis, 4 degrees of freedom. Error bars indicate standard deviation. SWAT: ChREBP F(4,21) = 10, p = 0.0001; Acly F(4,21) = 30.0, p = 2.0×10−8; Fasn F(4,21) = 8.8, p = 0.0002; MWAT: ChREBP F(4,18) = 8.6, p = 0.0004; Acly F(4,18) = 29.9, p = 9.9×10−8; Fasn F(4,18) = 5.3, p = 0.0.005; EWAT: ChREBP F(4,20) = 2.8, p = 0.055; Acly F(4,20) = 1.4, p = 0.25; Fasn F(4,20) = 0.82, p = 0.53.

Mentions: Testosterone has previously been shown to repress expression of genes encoding lipogenic enzymes in adipose tissue [42]. Array data from our present study showed that expression of the Ar is higher in EWAT than in MWAT and SWAT (data not shown). In a follow-up RT-PCR analysis the increased expression of Ar in EWAT compared to other adipose depots was confirmed (Figure 7A). Furthermore, Ar expression appeared to be higher in proximal EWAT than in distal EWAT, and we observed that Ar expression and de novo lipogenesis activity were negatively correlated (Figure 7B). A negative correlation was also observed between expression of Ar and expression of genes encoding fatty acid synthetase (Pearson correlation -0.43, one-sided significance 0.05) and ATP citrate lyase (Pearson correlation −0.43, one-sided significance 0.05). Ar expression was not affected by diet. The negative correlation between Ar expression and de novo lipogenesis activity was only observed on chow diet, whereas we did not examine the Ar expression in detail on HFD.


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)

Rate of lipogenesis and expression of putative regulatory factors.A) Gene expression levels of the androgen receptor (Ar) in proximal and distal epididymal (EWAT) adipose tissue, in mesenteric (MWAT), and in subcutaneous (SWAT) adipose tissue determined by RT-PCR. B) Expression of the gene encoding the androgen receptor (Ar) determined by RT-PCR plotted against rate of lipogenesis measured by incorporation of [14C]glucose in TAG in adipose tissue explants. C) Expression of carbohydrate responsive element binding protein (ChREBP), ATP citrate lyase (Acly) and fatty acid synthase (Fasn) on 12 weeks of high-fat diet determined by microarray analysis. The expression level at baseline was set to 1 for all genes. (A) Ar 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). MWAT-EWAT proximal U(5) = 0, p = 0.009; SWAT-EWAT proximal U(5) = 1, 0.02; EWAT proximal-EWAT distal U(5) = 3, p = 0.05 (B) the relation between lipogenesis and Ar expression was determined by Pearson correlation coefficient with one-sided significance calculated by Cronbach's Alpha, (C) *p<0.05 (one way ANOVA with Tukey post hoc analysis, 4 degrees of freedom. Error bars indicate standard deviation. SWAT: ChREBP F(4,21) = 10, p = 0.0001; Acly F(4,21) = 30.0, p = 2.0×10−8; Fasn F(4,21) = 8.8, p = 0.0002; MWAT: ChREBP F(4,18) = 8.6, p = 0.0004; Acly F(4,18) = 29.9, p = 9.9×10−8; Fasn F(4,18) = 5.3, p = 0.0.005; EWAT: ChREBP F(4,20) = 2.8, p = 0.055; Acly F(4,20) = 1.4, p = 0.25; Fasn F(4,20) = 0.82, p = 0.53.
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Related In: Results  -  Collection

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pone-0011525-g007: Rate of lipogenesis and expression of putative regulatory factors.A) Gene expression levels of the androgen receptor (Ar) in proximal and distal epididymal (EWAT) adipose tissue, in mesenteric (MWAT), and in subcutaneous (SWAT) adipose tissue determined by RT-PCR. B) Expression of the gene encoding the androgen receptor (Ar) determined by RT-PCR plotted against rate of lipogenesis measured by incorporation of [14C]glucose in TAG in adipose tissue explants. C) Expression of carbohydrate responsive element binding protein (ChREBP), ATP citrate lyase (Acly) and fatty acid synthase (Fasn) on 12 weeks of high-fat diet determined by microarray analysis. The expression level at baseline was set to 1 for all genes. (A) Ar 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). MWAT-EWAT proximal U(5) = 0, p = 0.009; SWAT-EWAT proximal U(5) = 1, 0.02; EWAT proximal-EWAT distal U(5) = 3, p = 0.05 (B) the relation between lipogenesis and Ar expression was determined by Pearson correlation coefficient with one-sided significance calculated by Cronbach's Alpha, (C) *p<0.05 (one way ANOVA with Tukey post hoc analysis, 4 degrees of freedom. Error bars indicate standard deviation. SWAT: ChREBP F(4,21) = 10, p = 0.0001; Acly F(4,21) = 30.0, p = 2.0×10−8; Fasn F(4,21) = 8.8, p = 0.0002; MWAT: ChREBP F(4,18) = 8.6, p = 0.0004; Acly F(4,18) = 29.9, p = 9.9×10−8; Fasn F(4,18) = 5.3, p = 0.0.005; EWAT: ChREBP F(4,20) = 2.8, p = 0.055; Acly F(4,20) = 1.4, p = 0.25; Fasn F(4,20) = 0.82, p = 0.53.
Mentions: Testosterone has previously been shown to repress expression of genes encoding lipogenic enzymes in adipose tissue [42]. Array data from our present study showed that expression of the Ar is higher in EWAT than in MWAT and SWAT (data not shown). In a follow-up RT-PCR analysis the increased expression of Ar in EWAT compared to other adipose depots was confirmed (Figure 7A). Furthermore, Ar expression appeared to be higher in proximal EWAT than in distal EWAT, and we observed that Ar expression and de novo lipogenesis activity were negatively correlated (Figure 7B). A negative correlation was also observed between expression of Ar and expression of genes encoding fatty acid synthetase (Pearson correlation -0.43, one-sided significance 0.05) and ATP citrate lyase (Pearson correlation −0.43, one-sided significance 0.05). Ar expression was not affected by diet. The negative correlation between Ar expression and de novo lipogenesis activity was only observed on chow diet, whereas we did not examine the Ar expression in detail on HFD.

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