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.

The renin angiotensin system (RAS) is a major regulator of blood pressure, fluid, and electrolyte homeostasis. RAS precursor angiotensinogen (Agt) is cleaved into angiotensin I (Ang I) and II (Ang II) by renin and angiotensin converting enzyme (ACE), respectively. Major effects of Ang II, the main bioactive peptide of this system, is mediated by G protein coupled receptors, Angiotensin Type 1 (AGTR1, AT1R) and Type 2 (AGTR2, AT2R) receptors. Further, the discovery of additional RAS peptides such as Ang 1-7 generated by the action of another enzyme ACE2 identified novel functions of this complex system. In addition to the systemic RAS, several local RAS exist in organs such as the brain, kidney, pancreas, and adipose tissue. The expression and regulation of various components of RAS in adipose tissue prompted extensive research into the role of adipose RAS in metabolic diseases. Indeed, animal studies have shown that adipose-derived Agt contributes to circulating RAS, kidney, and blood pressure regulation. Further, mice overexpressing Agt have high blood pressure and increased adiposity characterized by inflammation, adipocyte hypertrophy, and insulin resistance, which can be reversed at least in part by RAS inhibition. These findings highlight the importance of this system in energy homeostasis, especially in the context of obesity. This overview article discusses the depot-specific functions of adipose RAS, genetic and pharmacological manipulations of RAS, and its applications to adipogenesis, thermogenesis, and overall energy homeostasis. © 2017 American Physiological Society. Compr Physiol 7:1137-1150, 2017.

Obesity is an increasingly costly and widespread epidemic, effecting 1 in 10 adults worldwide. It has been causally linked with both the metabolic syndrome and insulin resistance, both of which are associated with increased chronic inflammation. The exact mechanisms through which inflammation may contribute to both MetS and IR are numerous and their details are still largely unknown. Recently, micro-RNAs (miRNAs) have emerged as potential interventional targets due to their potential preventive roles in the pathogenesis of several diseases, including MetS and obesity. The purpose of this review paper is to discuss some of the known roles of miRNAs as mediators of inflammation-associated obesity and IR and how omega-3 polyunsaturated fatty acids may be used as a nutritional intervention for these disorders.

Scope: Brown adipose tissue (BAT) dissipates energy through uncoupling protein 1 (UCP1) and has been proposed as an anti-obesity target. It was reported previously that a high-fat (HF) diet enriched in eicosapentaenoic acid (EPA) significantly increased UCP1 and other thermogenic markers in BAT. It is hypothesized that these effects are mediated through UCP1-dependent regulation. Methods and results: Wild-type (WT) and UCP1 knockout (KO) B6 male mice were housed at thermoneutrality and fed a HF diet, without or with eicosapentaenoic acid (EPA)-enriched fish oil. HF-fed KO mice were heavier and had higher BAT lipid content than other groups. Protective effects of EPA in WT, previously observed at 22°C (reduced adiposity, improved glucose tolerance, and increased UCP1), disappeared at thermoneutrality. Mitochondrial proteins, cytochrome c oxidase subunit 1 (COX I

Brown adipose tissue (BAT) dissipates chemical energy as heat via thermogenesis and protects against obesity by increasing energy expenditure. However, regulation of BAT by dietary factors remains largely unexplored at the mechanistic level. We investigated the effect of eicosapentaenoic acid (EPA) on BAT metabolism. Male C57BL/6J (B6) mice fed either a high-fat diet (HF, 45% kcal fat) or HF diet supplemented with EPA (HF-EPA, 6.75% kcal EPA) were used for 11 weeks. RNA sequencing (RNA-Seq) and microRNA (miRNA) profiling were performed on RNA from BAT using Illumina HiSeq and miSeq respectively. We conducted pathway analyses using ingenuity pathway analysis software (IPA®) and validated some genes and miRNAs using qPCR. We identified 479 genes that were differentially expressed (2-fold change, n=3, p ≤ 0.05) in BAT from HF compared to HF-EPA. Genes negatively correlated with thermogenesis such as hypoxia Inducible factor 1 alpha subunit inhibitor (Hif1αn), was downregulated by EPA. Pathways related to thermogenesis such as peroxisome proliferator-activated receptor (PPAR) were upregulated by EPA while pathways associated with obesity and inflammation such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were downregulated by EPA. MiRNA profiling identified nine and six miRNAs that were upregulated and downregulated by EPA, respectively (log2 fold change > 1.25, n=3, P ≤ 0.05). Key regulatory miRNAs were involved in thermogenesis, such as miR-455–3p and miR-129–5p were validated using qPCR. In conclusion, the depth of transcriptomic and miRNA profiling revealed novel mRNA-miRNA interaction networks in BAT which are involved in thermogenesis which regulated by EPA.