n3 and n6 polyunsaturated fatty acids differentially modulate prostaglandin E secretion but not markers of lipogenesis in adipocytes

Abstract

A dramatic rise in the incidence of obesity in the U.S. has accelerated the search for interventions that may impact this epidemic. One recently recognized target for such intervention is adipose tissue, which secretes a variety of bioactive substances including prostaglandins. Prostaglandin E 2 (PGE 2 ) has been shown to decrease lipolysis in adipocytes, but limited studies have explored alternative mechanisms by which PGE 2 might impact obesity, such as adipogenesis or lipogenesis. Studies conducted on Apc Min/+ mice indicated that selective inhibition of the cyclooxygenase (COX)-2 enzyme led to significant reductions in fatty acid synthase (FAS) activity in adipose tissue suggesting lipogenic effects of PGE 2 . To further investigate whether these lipid mediators directly regulate lipogenesis, we used 3T3-L1 adipocytes to determine the impact of eicosapentaenoic acid (EPA) and celecoxib on PGE 2 formation and FAS used as a lipogenic marker. Both arachidonic acid (AA) and EPA dose-dependently increased PGE secretion from adipocytes. AA was expectedly more potent and exhibiting at 150 uM dose a 5-fold increase in PGE 2 secretion over EPA. Despite higher secretion of PGE by EPA and AA compared to control, neither PUFA significantly altered FAS activity. By contrast both AA and EPA significantly decreased FAS mRNA levels. Addition of celecoxib, a selective COX-2 inhibitor, significantly decreased PGE 2 secretion (p < 0.05) versus control, and also significantly decreased FAS activity (p < 0.05). Unexpectedly, the combination of exogenous PGE 2 and celecoxib further decreased the FAS activity compared to PGE 2 alone or untreated controls. In conclusion, EPA-mediated inhibition of AA metabolism did not significantly alter FAS activity while both AA and EPA significantly decreased FAS mRNA expression. COX-2 inhibition significantly decreased PGE 2 production resulting in a decrease in FAS activity and expression that was not reversed with the addition of exogenous PGE 2 , suggesting an additional mechanism that is independent of COX-2.

n-3 and n-6 polyunsaturated fatty acids differentially regulate adipose angiotensinogen and other inflammatory adipokines in part via NF-κB-dependent mechanisms

“…3T3-L1 mouse embryonic preadipocytes were cultured as we previously described [34]. Briefly, 3T3-L1 cells were cultured in regular growth media consisting of Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin (P/S).…”

“…Differentiated cells were treated with varying concentrations of EPA and AA, as we previously described [34]. Briefly, the fatty acids were reconstituted in dimethyl sulfoxide (DMSO) and then conjugated to fatty-acid-free BSA by agitation in a 37°C water bath for 2 h prior to treatments.…”

“…Omega-3 (n-3) polyunsaturated fatty acids (n-3 PUFAs) such as eicosapentaenoic acid (EPA) are anti-inflammatory nutrients known to suppress the activation of NF-κB in several tissues [29]. We and other investigators have previously shown that n-6 PUFAs increase the secretion of proinflammatory substances such as prostaglandins (PGE 2 ) in adipocytes and that n-3 PUFAs counteracted these effects [30][31][32][33][34]. Therefore, we hypothesized that n-3 PUFA can decrease secretion of Agt and other inflammatory cytokines from adipocytes and that these effects are at least partially due to reduced NF-κB activation in adipocytes.…”

Difference in fatty acid composition and related nutritional indices of meat between two lines of slow-growing chickens slaughtered at different ages

“…It is well known that the higher intake of saturated fatty acid (SFA) in the human diet increases the risk of the development of coronary heart disease, atherosclerosis and can-cer (Mensink and Katan, 1992), whereas monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA), especially n-3, have a number of associated health benefits (Kris-Etherton, 1999;Siriwardhana et al, 2012). Foods rich in long-chain n-3 PUFA have been shown to improve cardiovascular health (Albert et al, 2002;Raitt et al, 2005;Harris, 2007;Lu et al, 2011), and reduce inflammation (Ferrucci et al, 2006;Calder, 2008;Fetterman and Zdanowicz, 2009;Wortman et al, 2009;Figueras et al, 2011) and behavioral disorders, such as depression (Rondanelli et al, 2011).…”

Soybean Oil: How Good or How Bad in Comparison with Other Dietary Oils in the Context of Colon Cancer

“…The effects of oils and fats in human nutrition have been largely discussed in the last decades, emphasizing the reduced intake of saturated and trans fatty acids and the increase in -3 intake (Wortman, Miyazaki et al 2009). ALA and LA are considered essential because they are not synthesized in the human body due to the lack of enzymes capable of inserting double bonds in the third and sixth carbons counted from the methyl terminal (Roynette, Calder et al 2004).…”