Insulin induces fatty acid desaturase expression in human monocytes

Abstract

Increasing evidence suggests that fatty acid desaturases, rate-limiting enzymes in unsaturated fatty acid biosynthesis, are important factors in the pathogenesis of lipid-induced insulin resistance. The conversion of dihomogamma linolenic acid (DGLA) into arachidonic acid (AA) in human plasma phospholipids has been shown to be regulated by insulin, suggesting a role for insulin in fatty acid desaturase 1 regulation. However insulin's role in monocyte inflammation associated with obesity and lifestyle disease development is uncertain. We therefore investigated if insulin is able to induce expression of stearoyl-CoA desaturase (SCD, Δ9 desaturase), fatty acid desaturase 1 (FADS1, Δ5 desaturase), and fatty acid desaturase 2 (FADS2, Δ6 desaturase), as well as the sterol regulatory element binding transcription factor 1-c (SREBP-1c) in monocytes. Here, for the first time, we demonstrate that THP-1 monocytes are insulin-responsive in inducing expression of SCD, FADS1, and FADS2 in a time- and dose-dependent manner. Understanding secondary consequences of postprandial hyperinsulinemia may open up new strategies for prevention and/or treatment of obesity-related metabolic complications.

Streptozotocin‐Induced Diabetes Partially Attenuates the Effects of a High‐Fat Diet on Liver and Brain Fatty Acid Composition in Mice

“…In addition, the High-fat diet increased the ratio of 18:1n-9 to 18:0, consistent with increased stearoyl-CoA desaturase-1 activity. Expression of stearoyl-CoA desaturase-1 is stimulated by insulin, and increased expression and activity of the enzyme are also associated with insulin resistance [45-47]. These findings have both similarities and differences with other studies of the effects of high-fat diets in rodents.…”

“…The High-fat diet also decreased the ratio of 18:3n-3 to 18:2n-6, suggesting a decrease in Δ6-desaturase activity. Insulin stimulates the activities of both Δ5- and Δ6-desaturases by inducing expression of FADS1 and FADS2 [44, 45], suggesting that some insulin-resistance may be occurring in the mice fed the High-fat diet. In addition, the High-fat diet increased the ratio of 18:1n-9 to 18:0, consistent with increased stearoyl-CoA desaturase-1 activity.…”

Eicosanoids in Metabolic Syndrome

“…Presently, the substrates for FADS3 have not been identified, although its upregulation during oxidative stress suggests a role in the prevention of lipotoxicity. FADS1 and FADS2 expression is increased by insulin, while FADS3 expression is mediated by PPARγ (Arbo et al, 2011; Reardon et al, 2012). There is a strong association of FADS2 gene with plasma liver enzyme levels, MetS, and type II diabetes mellitus (T2DM) (Chambers et al, 2011; Sergeant et al, 2012) and a negative association with FADS1.…”

N-3 fatty acid intake altered fat content and fatty acid distribution in chicken breast muscle, but did not influence mRNA expression of lipid-related enzymes

“…to obesity and insulin resistance [19-21]. The causes for these diseases are complex and multifactorial, but the amount of fat in muscle cells can be underlying the state of inflammation, insulin resistance and metabolic syndrome [22].…”