Delta-6 desaturase (Fads2) deficiency alters triacylglycerol/fatty acid cycling in murine white adipose tissue.

The Δ-6 desaturase (D6D) enzyme is not only critical for the synthesis of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from α-linolenic acid (ALA), but recent evidence suggests that it also plays a role in adipocyte lipid metabolism and body weight; however, the mechanisms remain largely unexplored. The goal of this study was to investigate if a D6D deficiency would inhibit triacylglycerol storage and alter lipolytic and lipogenic pathways in mouse white adipose tissue (WAT) depots due to a disruption in EPA and DHA production. Male C57BL/6J D6D knockout (KO) and wild-type (WT) mice were fed either a 7% w/w lard or flax (ALA rich) diet for 21 weeks. Energy expenditure, physical activity, and substrate utilization were measured with metabolic caging. Inguinal and epididymal WAT depots were analyzed for changes in tissue weight, fatty acid composition, adipocyte size, and markers of lipogenesis, lipolysis, and insulin signaling. KO mice had lower body weight, higher serum nonesterified fatty acids, smaller WAT depots, and reduced adipocyte size compared to WT mice without altered food intake, energy expenditure, or physical activity, regardless of the diet. Markers of lipogenesis and lipolysis were more highly expressed in KO mice compared to WT mice in both depots, regardless of the diet. These changes were concomitant with lower basal insulin signaling in WAT. Collectively, a D6D deficiency alters triacylglycerol/fatty acid cycling in WAT by promoting lipolysis and reducing fatty acid re-esterification, which may be partially attributed to a reduction in WAT insulin signaling.

Mechanisms underlying N3-PUFA regulation of white adipose tissue endocrine function.

Omega-3 polyunsaturated fatty acids (N3-PUFA) are widely reported to improve obesity-associated metabolic impairments, in part, through the regulation of adipokine and cytokine secretion from white adipose tissue (WAT). However, the precise underlying molecular mechanisms by which N3-PUFA influence WAT endocrine function remain poorly described. Available evidence supports that N3-PUFA and related bioactive lipid mediators regulate several intracellular pathways that converge on two important transcription factors: PPAR-γ and NF-κB. Further, N3-PUFA signaling through GPR120 appears integral for the regulation of adipokine and cytokine production. This review collates insights from in vitro and in vivo studies using genetic and chemical inhibition of key signaling proteins to describe the pathways by which N3-PUFA regulate WAT endocrine function. Existing gaps in knowledge and opportunities to advance our understanding in this area are also highlighted.