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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
Expression of genes encoding enzymes in fatty acid synthesis and processing during basal conditions (chow) and high-fat feeding.Expression of acetyl-CoA synthetase short-chain family member 2 (Acss2), pyruvate dehydrogenase α1 (Pdha1), pyruvate dehydrogenase β (Pdhb) dihydrolipoamide S-acetyltransferase (Dlat), ATP citrate lyase (Acly), fatty acid synthase (Fasn), long chain elongation enzymes Elovl5 and Elovl6 and stearoyl-CoA desaturase 1 and 2 (Scd1/2) in subcutaneous (SWAT), mesenteric (MWAT) and epididymal (EWAT) adipose tissue. The y-axis scale is the same for all three depots. Gene expression is given as relative expression. N at time-point 0, 1, 6, 9 and 12 weeks were 4, 5, 7, 3, 6 for epididymal adipose tissue (EWAT); 5, 6, 4, 6, 5 for subcutaneous adipose tissue (SWAT); and 3, 5, 4, 5, 7 for mesenteric adipose tissue (MWAT), respectively. Error bars indicate standard deviation. Statistically significant changes in expression over time are indicated by *(p<0.05 (one way ANOVA)). SWAT: Acss2 F(4,21) = 10.1, p = 9.8×10−5; Pdha1 F(4,21) = 17.9, p = 1.5×10−6; Pdhb F(4,21) = 15.3, p = 5.3×10−6; Dlat F(4,21) = 8.8, p = 0.0002; Acly F(4,21) = 30.0, p = 2.0×10−8; Fasn F(4,21) = 8.8, p = 0.0002; Elovl5 F(4,21) = 2.9, p = 0.04; Elovl6 F(4,21) = 27.5, p = 4.4×10−8; Scd1 F(4,21) = 0.9, p = 0.47; Scd2 F(4,21) = 2.2, p = 0.10; MWAT: Acss2 F(4,18) = 4.3, p = 0.013; Pdha1 F(4,18) = 9.9, p = 0.0002; Pdhb F(4,18) = 7.2, p = 0.001; Dlat F(4,18) = 4.6, p = 0.009; Acly F(4,18) = 29.9, p = 9.9×10−8; Fasn F(4,18) = 5.3, p = 0.0.005; Elovl5 F(4,18) = 9.7, p = 0.0002; Elovl6 F(4,18) = 14.4, p = 1.9×10−5; Scd1 F(4,18) = 2.0, p = 0.14; Scd2 F(4,18) = 0.42, p = 0.79; EWAT: Acss2 F(4,20) = 1.1, p = 0.37; Pdha1 F(4,20) = 1.9, p = 0.19; Pdhb F(4,20) = 2.3, p = 0.09; Dlat F(4,20) = 2.0, p = 0.12; Acly F(4,20) = 1.4, p = 0.25; Fasn F(4,20) = 0.82, p = 0.53; Elovl5 F(4,20) = 1.7, p = 0.28; Elovl6 F(4,20) = 1.2, p = 0.32; Scd1 F(4,20) = 5.1, p = 0.005; Scd2 F(4,20) = 3.4, p = 0.027.
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pone-0011525-g003: Expression of genes encoding enzymes in fatty acid synthesis and processing during basal conditions (chow) and high-fat feeding.Expression of acetyl-CoA synthetase short-chain family member 2 (Acss2), pyruvate dehydrogenase α1 (Pdha1), pyruvate dehydrogenase β (Pdhb) dihydrolipoamide S-acetyltransferase (Dlat), ATP citrate lyase (Acly), fatty acid synthase (Fasn), long chain elongation enzymes Elovl5 and Elovl6 and stearoyl-CoA desaturase 1 and 2 (Scd1/2) in subcutaneous (SWAT), mesenteric (MWAT) and epididymal (EWAT) adipose tissue. The y-axis scale is the same for all three depots. Gene expression is given as relative expression. N at time-point 0, 1, 6, 9 and 12 weeks were 4, 5, 7, 3, 6 for epididymal adipose tissue (EWAT); 5, 6, 4, 6, 5 for subcutaneous adipose tissue (SWAT); and 3, 5, 4, 5, 7 for mesenteric adipose tissue (MWAT), respectively. Error bars indicate standard deviation. Statistically significant changes in expression over time are indicated by *(p<0.05 (one way ANOVA)). SWAT: Acss2 F(4,21) = 10.1, p = 9.8×10−5; Pdha1 F(4,21) = 17.9, p = 1.5×10−6; Pdhb F(4,21) = 15.3, p = 5.3×10−6; Dlat F(4,21) = 8.8, p = 0.0002; Acly F(4,21) = 30.0, p = 2.0×10−8; Fasn F(4,21) = 8.8, p = 0.0002; Elovl5 F(4,21) = 2.9, p = 0.04; Elovl6 F(4,21) = 27.5, p = 4.4×10−8; Scd1 F(4,21) = 0.9, p = 0.47; Scd2 F(4,21) = 2.2, p = 0.10; MWAT: Acss2 F(4,18) = 4.3, p = 0.013; Pdha1 F(4,18) = 9.9, p = 0.0002; Pdhb F(4,18) = 7.2, p = 0.001; Dlat F(4,18) = 4.6, p = 0.009; Acly F(4,18) = 29.9, p = 9.9×10−8; Fasn F(4,18) = 5.3, p = 0.0.005; Elovl5 F(4,18) = 9.7, p = 0.0002; Elovl6 F(4,18) = 14.4, p = 1.9×10−5; Scd1 F(4,18) = 2.0, p = 0.14; Scd2 F(4,18) = 0.42, p = 0.79; EWAT: Acss2 F(4,20) = 1.1, p = 0.37; Pdha1 F(4,20) = 1.9, p = 0.19; Pdhb F(4,20) = 2.3, p = 0.09; Dlat F(4,20) = 2.0, p = 0.12; Acly F(4,20) = 1.4, p = 0.25; Fasn F(4,20) = 0.82, p = 0.53; Elovl5 F(4,20) = 1.7, p = 0.28; Elovl6 F(4,20) = 1.2, p = 0.32; Scd1 F(4,20) = 5.1, p = 0.005; Scd2 F(4,20) = 3.4, p = 0.027.

Mentions: Pathways involved in acetyl-CoA synthesis and pyruvate metabolism exhibited several regulated genes in MWAT and SWAT but not in EWAT. Acetyl-CoA is a precursor of de novo lipogenesis. To investigate in detail how fatty acid synthesis and processing are affected in adipose tissues by HFD, expression levels of genes involved in acetyl-CoA production and the down-stream metabolic pathways of fatty acid synthesis, elongation and desaturation, were plotted against time (Figure 3).


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)

Expression of genes encoding enzymes in fatty acid synthesis and processing during basal conditions (chow) and high-fat feeding.Expression of acetyl-CoA synthetase short-chain family member 2 (Acss2), pyruvate dehydrogenase α1 (Pdha1), pyruvate dehydrogenase β (Pdhb) dihydrolipoamide S-acetyltransferase (Dlat), ATP citrate lyase (Acly), fatty acid synthase (Fasn), long chain elongation enzymes Elovl5 and Elovl6 and stearoyl-CoA desaturase 1 and 2 (Scd1/2) in subcutaneous (SWAT), mesenteric (MWAT) and epididymal (EWAT) adipose tissue. The y-axis scale is the same for all three depots. Gene expression is given as relative expression. N at time-point 0, 1, 6, 9 and 12 weeks were 4, 5, 7, 3, 6 for epididymal adipose tissue (EWAT); 5, 6, 4, 6, 5 for subcutaneous adipose tissue (SWAT); and 3, 5, 4, 5, 7 for mesenteric adipose tissue (MWAT), respectively. Error bars indicate standard deviation. Statistically significant changes in expression over time are indicated by *(p<0.05 (one way ANOVA)). SWAT: Acss2 F(4,21) = 10.1, p = 9.8×10−5; Pdha1 F(4,21) = 17.9, p = 1.5×10−6; Pdhb F(4,21) = 15.3, p = 5.3×10−6; Dlat F(4,21) = 8.8, p = 0.0002; Acly F(4,21) = 30.0, p = 2.0×10−8; Fasn F(4,21) = 8.8, p = 0.0002; Elovl5 F(4,21) = 2.9, p = 0.04; Elovl6 F(4,21) = 27.5, p = 4.4×10−8; Scd1 F(4,21) = 0.9, p = 0.47; Scd2 F(4,21) = 2.2, p = 0.10; MWAT: Acss2 F(4,18) = 4.3, p = 0.013; Pdha1 F(4,18) = 9.9, p = 0.0002; Pdhb F(4,18) = 7.2, p = 0.001; Dlat F(4,18) = 4.6, p = 0.009; Acly F(4,18) = 29.9, p = 9.9×10−8; Fasn F(4,18) = 5.3, p = 0.0.005; Elovl5 F(4,18) = 9.7, p = 0.0002; Elovl6 F(4,18) = 14.4, p = 1.9×10−5; Scd1 F(4,18) = 2.0, p = 0.14; Scd2 F(4,18) = 0.42, p = 0.79; EWAT: Acss2 F(4,20) = 1.1, p = 0.37; Pdha1 F(4,20) = 1.9, p = 0.19; Pdhb F(4,20) = 2.3, p = 0.09; Dlat F(4,20) = 2.0, p = 0.12; Acly F(4,20) = 1.4, p = 0.25; Fasn F(4,20) = 0.82, p = 0.53; Elovl5 F(4,20) = 1.7, p = 0.28; Elovl6 F(4,20) = 1.2, p = 0.32; Scd1 F(4,20) = 5.1, p = 0.005; Scd2 F(4,20) = 3.4, p = 0.027.
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pone-0011525-g003: Expression of genes encoding enzymes in fatty acid synthesis and processing during basal conditions (chow) and high-fat feeding.Expression of acetyl-CoA synthetase short-chain family member 2 (Acss2), pyruvate dehydrogenase α1 (Pdha1), pyruvate dehydrogenase β (Pdhb) dihydrolipoamide S-acetyltransferase (Dlat), ATP citrate lyase (Acly), fatty acid synthase (Fasn), long chain elongation enzymes Elovl5 and Elovl6 and stearoyl-CoA desaturase 1 and 2 (Scd1/2) in subcutaneous (SWAT), mesenteric (MWAT) and epididymal (EWAT) adipose tissue. The y-axis scale is the same for all three depots. Gene expression is given as relative expression. N at time-point 0, 1, 6, 9 and 12 weeks were 4, 5, 7, 3, 6 for epididymal adipose tissue (EWAT); 5, 6, 4, 6, 5 for subcutaneous adipose tissue (SWAT); and 3, 5, 4, 5, 7 for mesenteric adipose tissue (MWAT), respectively. Error bars indicate standard deviation. Statistically significant changes in expression over time are indicated by *(p<0.05 (one way ANOVA)). SWAT: Acss2 F(4,21) = 10.1, p = 9.8×10−5; Pdha1 F(4,21) = 17.9, p = 1.5×10−6; Pdhb F(4,21) = 15.3, p = 5.3×10−6; Dlat F(4,21) = 8.8, p = 0.0002; Acly F(4,21) = 30.0, p = 2.0×10−8; Fasn F(4,21) = 8.8, p = 0.0002; Elovl5 F(4,21) = 2.9, p = 0.04; Elovl6 F(4,21) = 27.5, p = 4.4×10−8; Scd1 F(4,21) = 0.9, p = 0.47; Scd2 F(4,21) = 2.2, p = 0.10; MWAT: Acss2 F(4,18) = 4.3, p = 0.013; Pdha1 F(4,18) = 9.9, p = 0.0002; Pdhb F(4,18) = 7.2, p = 0.001; Dlat F(4,18) = 4.6, p = 0.009; Acly F(4,18) = 29.9, p = 9.9×10−8; Fasn F(4,18) = 5.3, p = 0.0.005; Elovl5 F(4,18) = 9.7, p = 0.0002; Elovl6 F(4,18) = 14.4, p = 1.9×10−5; Scd1 F(4,18) = 2.0, p = 0.14; Scd2 F(4,18) = 0.42, p = 0.79; EWAT: Acss2 F(4,20) = 1.1, p = 0.37; Pdha1 F(4,20) = 1.9, p = 0.19; Pdhb F(4,20) = 2.3, p = 0.09; Dlat F(4,20) = 2.0, p = 0.12; Acly F(4,20) = 1.4, p = 0.25; Fasn F(4,20) = 0.82, p = 0.53; Elovl5 F(4,20) = 1.7, p = 0.28; Elovl6 F(4,20) = 1.2, p = 0.32; Scd1 F(4,20) = 5.1, p = 0.005; Scd2 F(4,20) = 3.4, p = 0.027.
Mentions: Pathways involved in acetyl-CoA synthesis and pyruvate metabolism exhibited several regulated genes in MWAT and SWAT but not in EWAT. Acetyl-CoA is a precursor of de novo lipogenesis. To investigate in detail how fatty acid synthesis and processing are affected in adipose tissues by HFD, expression levels of genes involved in acetyl-CoA production and the down-stream metabolic pathways of fatty acid synthesis, elongation and desaturation, were plotted against time (Figure 3).

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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