Eicosapentaenoic acid regulates brown adipose tissue metabolism in high-fat-fed mice and in clonal brown adipocytes

Abstract

Brown adipose tissue (BAT) plays a key role in energy expenditure through its specialized thermogenic function. Therefore, BAT activation may help prevent and/or treat obesity. Interestingly, subcutaneous white adipose tissue (WAT) also has the ability to differentiate into brown-like adipocytes and may potentially contribute to increased thermogenesis. We have previously reported that eicosapentaenoic acid (EPA) reduces high-fat (HF)-diet-induced obesity and insulin resistance in mice. Whether BAT mediates some of these beneficial effects of EPA has not been determined. We hypothesized that EPA activates BAT thermogenic program, contributing to its antiobesity effects. BAT and WAT were harvested from B6 male mice fed HF diets supplemented with or without EPA. HIB 1B clonal brown adipocytes treated with or without EPA were also used. Gene and protein expressions were measured in adipose tissues and H1B 1B cells by quantitative polymerase chain reaction and immunoblotting, respectively. Our results show that BAT from EPA-supplemented mice expressed significantly higher levels of thermogenic genes such as PRDM16 and PGC1α and higher levels of uncoupling protein 1 compared to HF-fed mice. By contrast, both WATs (subcutaneous and visceral) had undetectable levels of these markers with no up regulation by EPA. HIB 1B cells treated with EPA showed significantly higher mRNA expression of PGC1α and SIRT2. EPA treatment significantly increased maximum oxidative and peak glycolytic metabolism in H1B 1B cells. Our results demonstrate a novel and promising role for EPA in preventing obesity via activation of BAT, adding to its known beneficial anti-inflammatory effects.

Resolvin E1 derived from eicosapentaenoic acid prevents hyperinsulinemia and hyperglycemia in a host genetic manner

“…The preventative studies with pure EPA ethyl esters challenge some previous findings in this area of study. Earlies studies have reported a reduction in fat mass with EPA-enriched oils, which we did not observe 43,44 . Perhaps the differences in results lies in the concentration and purity of EPA and the timing as well as duration of intervention.…”

Transcriptomic and microRNA analyses of gene networks regulated by eicosapentaenoic acid in brown adipose tissue of diet-induced obese mice

“…In the previous report [11], we investigated the effects of both EPA and DHA on cultured brown adipocytes. We observed more mitochondrial content with EPA than DHA.…”

“…Ppar-α is highly expressed in BAT and increases levels of thermogenic marker including Pgc1α and Ucp1 [46], all of which are suitable targets for BAT activation and metabolic disorders. Moreover, some studies have already reported that n-3 PUFAs induce thermogenesis in BAT by increasing the level of Ppar-α and Pparγ [47–49]. Beside the activation of BAT, omega 3 fatty acids act as natural ligands and activators of Ppar-α , which blocks NF-KB activity in WAT to prevent inflammation [50].…”

“…Moreover, our laboratory has reported that feeding a high-fat (HF) diet enriched with EPA to mice significantly reduced body weight, fat mass and glucose intolerance while improving insulin sensitivity and inflammation (to levels comparable to low-fat fed mice) [10]. Additionally, we recently reported that EPA increased levels of several classical thermogenic biomarkers at both gene and protein levels in BAT of mice fed EPA and in clonal brown adipocytes [11]. …”

Involvement of polyunsaturated fatty acids in the control of energy storage and expenditure

“…However, it also has been shown that v3 PUFAs favored the formation of the so-called "healthy adipocytes" with high number of mitochondria but not expressing UCP1 (Kuda et al, 2018). Moreover, other studies have shown the beneficial effect of v3 PUFA supplementation on glucose metabolism (glucose tolerance, insulin sensitivity) and on BAT activation and/or brite adipocyte formation (Kim and Goto, 2015;Pahlavani et al, 2017). In vivo studies have shown a global increase in thermogenesis in mice fed fish oil v3-enriched food, i.e.…”