Limits...
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
Fatty acid profiles of adipose tissues.Proportions of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), linoleic acid (18∶2 ω-6) and α-linolenic acid (18∶3 ω-3) in proximal epididymal and distal epididymal (EWAT) adipose tissue, in mesenteric (MWAT), and in subcutaneous (SWAT) adipose tissue on chow feeding. SFA, linoleic acid and α-linolenic acid but not MUFA 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). Error bars indicate standard deviation. SFA: MWAT-EWAT proximal U(5) = 0, p = 0.009; SWAT-EWAT proximal U(5) = 1, 0.02; EWAT proximal-EWAT distal U(5) = 12, p = 0.9; MUFA: MWAT-EWAT proximal U(5) = 7, p = 0.25; SWAT-EWAT proximal U(5) = 9, 0.46; EWAT proximal-EWAT distal U(5) = 11, p = 0.75; linoleic acid: MWAT-EWAT proximal U(5) = 0, p = 0.009; SWAT-EWAT proximal U(5) = 0, 0.009; EWAT proximal-EWAT distal U(5) = 10, p = 0.6; α-linolenic acid: MWAT-EWAT proximal U(5) = 0, p = 0.009; SWAT-EWAT proximal U(5) = 2, 0.03; EWAT proximal-EWAT distal U(5) = 7, p = 0.25.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2902507&req=5

pone-0011525-g008: Fatty acid profiles of adipose tissues.Proportions of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), linoleic acid (18∶2 ω-6) and α-linolenic acid (18∶3 ω-3) in proximal epididymal and distal epididymal (EWAT) adipose tissue, in mesenteric (MWAT), and in subcutaneous (SWAT) adipose tissue on chow feeding. SFA, linoleic acid and α-linolenic acid but not MUFA 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). Error bars indicate standard deviation. SFA: MWAT-EWAT proximal U(5) = 0, p = 0.009; SWAT-EWAT proximal U(5) = 1, 0.02; EWAT proximal-EWAT distal U(5) = 12, p = 0.9; MUFA: MWAT-EWAT proximal U(5) = 7, p = 0.25; SWAT-EWAT proximal U(5) = 9, 0.46; EWAT proximal-EWAT distal U(5) = 11, p = 0.75; linoleic acid: MWAT-EWAT proximal U(5) = 0, p = 0.009; SWAT-EWAT proximal U(5) = 0, 0.009; EWAT proximal-EWAT distal U(5) = 10, p = 0.6; α-linolenic acid: MWAT-EWAT proximal U(5) = 0, p = 0.009; SWAT-EWAT proximal U(5) = 2, 0.03; EWAT proximal-EWAT distal U(5) = 7, p = 0.25.

Mentions: High lipogenic activity in adipose tissue has been reported to be positively correlated with the content of saturated fatty acids [46]. The mechanistic background for this relationship is unknown but saturated fatty acids are the end products of de novo lipogenesis and it is possible that local lipogenic rate affects the stoichiometric relationship between stored fatty acids in favor of saturated fatty acids. To investigate if the observed site-specific differences in de novo lipogenesis (Figure 5) are related to differences in fatty acid composition, targeted lipidomics was performed on MWAT, SWAT, and the proximal and distal EWAT on chow diet. Indeed, a strong correlation between de novo lipogenesis activity and fatty acid composition was found. The total content of saturated fatty acids ranged from 30% in MWAT to 21% in proximal EWAT (Figure 8). Saturated fatty acids with even carbon number (14∶0–20∶0) exhibited similar proportions between depots (Figure 8), whereas the low content of saturated fatty acids with odd carbon numbers (15∶0 and 17∶0) was similar in all depots (data not shown). EWAT was enriched in linoleic acid (18∶2 ω-6) and α-linolenic acid (18∶3 ω-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)

Fatty acid profiles of adipose tissues.Proportions of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), linoleic acid (18∶2 ω-6) and α-linolenic acid (18∶3 ω-3) in proximal epididymal and distal epididymal (EWAT) adipose tissue, in mesenteric (MWAT), and in subcutaneous (SWAT) adipose tissue on chow feeding. SFA, linoleic acid and α-linolenic acid but not MUFA 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). Error bars indicate standard deviation. SFA: MWAT-EWAT proximal U(5) = 0, p = 0.009; SWAT-EWAT proximal U(5) = 1, 0.02; EWAT proximal-EWAT distal U(5) = 12, p = 0.9; MUFA: MWAT-EWAT proximal U(5) = 7, p = 0.25; SWAT-EWAT proximal U(5) = 9, 0.46; EWAT proximal-EWAT distal U(5) = 11, p = 0.75; linoleic acid: MWAT-EWAT proximal U(5) = 0, p = 0.009; SWAT-EWAT proximal U(5) = 0, 0.009; EWAT proximal-EWAT distal U(5) = 10, p = 0.6; α-linolenic acid: MWAT-EWAT proximal U(5) = 0, p = 0.009; SWAT-EWAT proximal U(5) = 2, 0.03; EWAT proximal-EWAT distal U(5) = 7, p = 0.25.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2902507&req=5

pone-0011525-g008: Fatty acid profiles of adipose tissues.Proportions of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), linoleic acid (18∶2 ω-6) and α-linolenic acid (18∶3 ω-3) in proximal epididymal and distal epididymal (EWAT) adipose tissue, in mesenteric (MWAT), and in subcutaneous (SWAT) adipose tissue on chow feeding. SFA, linoleic acid and α-linolenic acid but not MUFA 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). Error bars indicate standard deviation. SFA: MWAT-EWAT proximal U(5) = 0, p = 0.009; SWAT-EWAT proximal U(5) = 1, 0.02; EWAT proximal-EWAT distal U(5) = 12, p = 0.9; MUFA: MWAT-EWAT proximal U(5) = 7, p = 0.25; SWAT-EWAT proximal U(5) = 9, 0.46; EWAT proximal-EWAT distal U(5) = 11, p = 0.75; linoleic acid: MWAT-EWAT proximal U(5) = 0, p = 0.009; SWAT-EWAT proximal U(5) = 0, 0.009; EWAT proximal-EWAT distal U(5) = 10, p = 0.6; α-linolenic acid: MWAT-EWAT proximal U(5) = 0, p = 0.009; SWAT-EWAT proximal U(5) = 2, 0.03; EWAT proximal-EWAT distal U(5) = 7, p = 0.25.
Mentions: High lipogenic activity in adipose tissue has been reported to be positively correlated with the content of saturated fatty acids [46]. The mechanistic background for this relationship is unknown but saturated fatty acids are the end products of de novo lipogenesis and it is possible that local lipogenic rate affects the stoichiometric relationship between stored fatty acids in favor of saturated fatty acids. To investigate if the observed site-specific differences in de novo lipogenesis (Figure 5) are related to differences in fatty acid composition, targeted lipidomics was performed on MWAT, SWAT, and the proximal and distal EWAT on chow diet. Indeed, a strong correlation between de novo lipogenesis activity and fatty acid composition was found. The total content of saturated fatty acids ranged from 30% in MWAT to 21% in proximal EWAT (Figure 8). Saturated fatty acids with even carbon number (14∶0–20∶0) exhibited similar proportions between depots (Figure 8), whereas the low content of saturated fatty acids with odd carbon numbers (15∶0 and 17∶0) was similar in all depots (data not shown). EWAT was enriched in linoleic acid (18∶2 ω-6) and α-linolenic acid (18∶3 ω-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.

Show MeSH