Diets Containing α-Linolenic (ω3) or Oleic (ω9) Fatty Acids Rescues Obese Mice From Insulin Resistance

Abstract

Subclinical systemic inflammation is a hallmark of obesity and insulin resistance. The results obtained from a number of experimental studies suggest that targeting different components of the inflammatory machinery may result in the improvement of the metabolic phenotype. Unsaturated fatty acids exert antiinflammatory activity through several distinct mechanisms. Here, we tested the capacity of ω3 and ω9 fatty acids, directly from their food matrix, to exert antiinflammatory activity through the G protein-coupled receptor (GPR)120 and GPR40 pathways. GPR120 was activated in liver, skeletal muscle, and adipose tissues, reverting inflammation and insulin resistance in obese mice. Part of this action was also mediated by GPR40 on muscle, as a novel mechanism described. Pair-feeding and immunoneutralization experiments reinforced the pivotal role of GPR120 as a mediator in the response to the nutrients. The improvement in insulin sensitivity in the high-fat substituted diets was associated with a marked reduction in tissue inflammation, decreased macrophage infiltration, and increased IL-10 levels. Furthermore, improved glucose homeostasis was accompanied by the reduced expression of hepatic gluconeogenic enzymes and reduced body mass. Thus, our data indicate that GPR120 and GPR40 play a critical role as mediators of the beneficial effects of dietary unsaturated fatty acids in the context of obesity-induced insulin resistance.

Impact of physical exercise on visceral adipose tissue fatty acid profile and inflammation in response to a high-fat diet regimen

“…Several studies reported that specific FA, including SFA, MUFA and linoleic acid are implicated in the development of the inflammatory process during obesity (1,2,13,14).…”

“…Fatty acids (FA) are energy-rich molecules that play important physiological roles in several organs, including white adipose tissue (WAT) (1,2). In humans, the most abundant FA esterified to triglycerides are oleic (C18:1n9), palmitic (C16:0) and linoleic (C18:2n6) that account for over 85% of FA in WAT triglycerides (3).…”

“…Therefore, this inflammatory state triggers the secretion of macrophage chemoattractant protein (MCP)-1 by macrophages, which can either sustain a macrophage-like phenotype in undifferentiated precursor cells or diminish the ability of adipocytes to further expand and store lipids, thus supporting a deleterious "vicious cycle" (7,8). Some recent studies reported that specific FA, such as saturated fatty acids (SFA) (9,10), monounsaturated fatty acids (11) and n6-polyunsaturated fatty acids (PUFA) (12) are involved in the pathophysiology of inflammation during obesity (1,2,13,14). In fact, a fat diet rich in SFA likely enhance circulating biomarkers of (pro) inflammation in health individuals (10), and in vitro studies showed that macrophages exposed to SFA increased pro-inflammatory gene expression and cytokine secretion, such as TNF-α and IL-6, and the chemokine CXCL1/KC (9).…”

Hypothalamic Injury: Fish Oil to the Rescue!

“…The authors previously reported that partially replacing saturated fatty acids (SFAs) with v-3 in the diet led to reduced body fat mass, improved leptin, and better glucose sensitivity (14,15). They now show that this dietary intervention also specifically increases neurogenesis and the number of dividing cells in the arcuate and the paraventricular nuclei of the hypothalamus.…”

“…Recent studies of Velloso and colleagues (14) also have reported anti-inflammatory effects of v-3 fatty acids in both the brain and peripheral tissues, which are mediated through the actions of GPR120 and GPR40. They show that the activation of these receptors by v-3 fatty acids can reverse inflammation and insulin resistance in obese mice (15). Clinical trials focusing on pharmacological targeting of GPR40 have also demonstrated that GPR40 is capable of stimulating insulin secretion and lowering blood glucose levels (19).…”