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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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Model for site-specific androgen control of lipogenesis promoting enrichment of essential fatty acids in the proximal epididymal adipose tissue.Androgen suppression of adipose tissue de novo lipogenesis is regulated by androgen receptor (Ar). Ar is highly expressed in proximal epididymal adipose tissue (EWATp). Low rate of de novo lipogenesis causes high content of dietary fatty acids and on chow diet the essential fatty acids linoleic acid and α-linolenic acid accumulate. Delta-6 and delta-5 desaturase (D6D and D5D) in epididymis convert linoleic acid and α-linolenic acid into polyunsaturated fatty acids (PUFA) with 20 and 22 carbon atoms required for spermatogenesis. When animals are fed high-fat diet (HFD) rich in saturated fatty acids adipose tissue is depleted of PUFA, potentially resulting in impaired sperm quality and decreased fertility.
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pone-0011525-g009: Model for site-specific androgen control of lipogenesis promoting enrichment of essential fatty acids in the proximal epididymal adipose tissue.Androgen suppression of adipose tissue de novo lipogenesis is regulated by androgen receptor (Ar). Ar is highly expressed in proximal epididymal adipose tissue (EWATp). Low rate of de novo lipogenesis causes high content of dietary fatty acids and on chow diet the essential fatty acids linoleic acid and α-linolenic acid accumulate. Delta-6 and delta-5 desaturase (D6D and D5D) in epididymis convert linoleic acid and α-linolenic acid into polyunsaturated fatty acids (PUFA) with 20 and 22 carbon atoms required for spermatogenesis. When animals are fed high-fat diet (HFD) rich in saturated fatty acids adipose tissue is depleted of PUFA, potentially resulting in impaired sperm quality and decreased fertility.

Mentions: A major function of adipose tissue is storage of surplus energy. To carry out this task adipocyte metabolism is flexible and tightly influenced by energy balance. Excess dietary carbohydrates are transformed to fatty acids by de novo lipogenesis and stored as triacylglycerols. Thus, it is intriguing that the control of de novo lipogenesis in proximal EWAT is suppressed independent of diet, and that nutrient control appears to be abolished by sex-steroid control. We find that sperms are highly enriched in PUFA, especially DHA and arachidonic acid (Table S1) and propose a model where sex-steroids suppress de novo lipogenesis in adipose tissue associated with the testicles and thereby optimize this tissue for storage of dietary fatty acids as precursors during spermatogenesis (Figure 9). According to this model linoleic acid and α-linolenic acid are transported from EWAT to epididymis and potentially to testis where they are processed by delta-5 and delta-6 desaturases [55], [56]. Long term diet enriched in saturated and monounsaturated fatty acids will deplete the storage of linoleic acid and α-linolenic acid, and eventually also change the fatty acid composition of the sperms. It has been shown that sperms isolated from animals kept on fat-free diet for six weeks exhibit only slightly reduced levels of PUFA, indicating that stored fatty acids are used as building blocks during spermatogenesis and can sustain the demand over long periods of time with insufficient dietary fatty acid supply [55]. Removal of epididymal adipose tissue abolish spermatogenesis [57], [58] but does not influence Leidig cell structure or testosterone production [58]. Furthermore, a transgenic mouse model lacking white adipose tissue (male A-ZIP/F-1), exhibits reduced fertility independent of leptin and testosterone levels [59], suggesting a potential role for stored fatty acids in the production of viable sperms.


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)

Model for site-specific androgen control of lipogenesis promoting enrichment of essential fatty acids in the proximal epididymal adipose tissue.Androgen suppression of adipose tissue de novo lipogenesis is regulated by androgen receptor (Ar). Ar is highly expressed in proximal epididymal adipose tissue (EWATp). Low rate of de novo lipogenesis causes high content of dietary fatty acids and on chow diet the essential fatty acids linoleic acid and α-linolenic acid accumulate. Delta-6 and delta-5 desaturase (D6D and D5D) in epididymis convert linoleic acid and α-linolenic acid into polyunsaturated fatty acids (PUFA) with 20 and 22 carbon atoms required for spermatogenesis. When animals are fed high-fat diet (HFD) rich in saturated fatty acids adipose tissue is depleted of PUFA, potentially resulting in impaired sperm quality and decreased fertility.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0011525-g009: Model for site-specific androgen control of lipogenesis promoting enrichment of essential fatty acids in the proximal epididymal adipose tissue.Androgen suppression of adipose tissue de novo lipogenesis is regulated by androgen receptor (Ar). Ar is highly expressed in proximal epididymal adipose tissue (EWATp). Low rate of de novo lipogenesis causes high content of dietary fatty acids and on chow diet the essential fatty acids linoleic acid and α-linolenic acid accumulate. Delta-6 and delta-5 desaturase (D6D and D5D) in epididymis convert linoleic acid and α-linolenic acid into polyunsaturated fatty acids (PUFA) with 20 and 22 carbon atoms required for spermatogenesis. When animals are fed high-fat diet (HFD) rich in saturated fatty acids adipose tissue is depleted of PUFA, potentially resulting in impaired sperm quality and decreased fertility.
Mentions: A major function of adipose tissue is storage of surplus energy. To carry out this task adipocyte metabolism is flexible and tightly influenced by energy balance. Excess dietary carbohydrates are transformed to fatty acids by de novo lipogenesis and stored as triacylglycerols. Thus, it is intriguing that the control of de novo lipogenesis in proximal EWAT is suppressed independent of diet, and that nutrient control appears to be abolished by sex-steroid control. We find that sperms are highly enriched in PUFA, especially DHA and arachidonic acid (Table S1) and propose a model where sex-steroids suppress de novo lipogenesis in adipose tissue associated with the testicles and thereby optimize this tissue for storage of dietary fatty acids as precursors during spermatogenesis (Figure 9). According to this model linoleic acid and α-linolenic acid are transported from EWAT to epididymis and potentially to testis where they are processed by delta-5 and delta-6 desaturases [55], [56]. Long term diet enriched in saturated and monounsaturated fatty acids will deplete the storage of linoleic acid and α-linolenic acid, and eventually also change the fatty acid composition of the sperms. It has been shown that sperms isolated from animals kept on fat-free diet for six weeks exhibit only slightly reduced levels of PUFA, indicating that stored fatty acids are used as building blocks during spermatogenesis and can sustain the demand over long periods of time with insufficient dietary fatty acid supply [55]. Removal of epididymal adipose tissue abolish spermatogenesis [57], [58] but does not influence Leidig cell structure or testosterone production [58]. Furthermore, a transgenic mouse model lacking white adipose tissue (male A-ZIP/F-1), exhibits reduced fertility independent of leptin and testosterone levels [59], suggesting a potential role for stored fatty acids in the production of viable sperms.

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
Related in: MedlinePlus