Monounsaturated Fatty Acid–Enriched High-Fat Diets Impede Adipose NLRP3 Inflammasome–Mediated IL-1β Secretion and Insulin Resistance Despite Obesity

Abstract

Saturated fatty acid (SFA) high-fat diets (HFDs) enhance interleukin (IL)-1β–mediated adipose inflammation and insulin resistance. However, the mechanisms by which different fatty acids regulate IL-1β and the subsequent effects on adipose tissue biology and insulin sensitivity in vivo remain elusive. We hypothesized that the replacement of SFA for monounsaturated fatty acid (MUFA) in HFDs would reduce pro-IL-1β priming in adipose tissue and attenuate insulin resistance via MUFA-driven AMPK activation. MUFA-HFD–fed mice displayed improved insulin sensitivity coincident with reduced pro-IL-1β priming, attenuated adipose IL-1β secretion, and sustained adipose AMPK activation compared with SFA-HFD–fed mice. Furthermore, MUFA-HFD–fed mice displayed hyperplastic adipose tissue, with enhanced adipogenic potential of the stromal vascular fraction and improved insulin sensitivity. In vitro, we demonstrated that the MUFA oleic acid can impede ATP-induced IL-1β secretion from lipopolysaccharide- and SFA-primed cells in an AMPK-dependent manner. Conversely, in a regression study, switching from SFA- to MUFA-HFD failed to reverse insulin resistance but improved fasting plasma insulin levels. In humans, high-SFA consumers, but not high-MUFA consumers, displayed reduced insulin sensitivity with elevated pycard-1 and caspase-1 expression in adipose tissue. These novel findings suggest that dietary MUFA can attenuate IL-1β–mediated insulin resistance and adipose dysfunction despite obesity via the preservation of AMPK activity.

Probiotic strains of lactobacilli and bifidobacteria alter pro- and anti-inflammatory cytokines production in rats with monosodium glutamate-induced obesity

“…It was found that the IL-1β, which is primed by high-fat diet (HFD) and is cleaved through the NLRP3 inflammasome complex [21,22], and which production in fat tissue is associated with the TLR4 receptor and nuclear factor-κB activation [23,24], directly influences the peripheral insulin resistance and type II diabetes [20,25,21,26,22]. In our study, glucose and insulin levels in blood serum, and HOMA insulin resistance index [16], as well as IL-1β and IL-12Br40 production were also increased in rats with MSG-induced obesity comparing with intact rats.…”

Suppression of NLRP3 inflammasome by γ-tocotrienol ameliorates type 2 diabetes

“…For instance, elevated levels of circulating FFAs were shown to activate the NLRP3 infl ammasome and weaken insulin sensitivity ( 27,28 ). In contrast, -3 FA ( 29 ) and MUFAs ( 30 ) have been shown to curtail NLRP3 Tanamoto ( 22 ), inhibition of proteasomal degradation by MG132 failed to rescue the ␥ T3-mediated decrease of TRAF6 or to increase K48-Ub of TRAF6 ( Fig. 6C ).…”

The new‐generation pan‐peroxisome proliferator‐activated receptor agonist IVA337 protects the liver from metabolic disorders and fibrosis

“…This effect of IVA337 might be due to PPARδ because it was previously shown that PPARδ activation decreases the expression of inflammasome components (NLRP3, caspase1, and IL‐1) when stimulated with palmitate (a saturated fatty acid) and lipopolysaccharides in hepatocytes 32. This effect could also be due to the PPARγ effect on SCD1 because saturated fatty acids activate the inflammasome whereas MUFAs inhibit the inflammasome components 26, 38. Overall, these results indicate that activation of PPARα, PPARδ, and PPARγ in the hepatocytes would contribute to the antisteatotic and anti‐inflammatory effect of IVA337 in the MCD and foz/foz models.…”