Palmitoleic Acid (N-7) Attenuates the Immunometabolic Disturbances Caused by a High-Fat Diet Independently of PPARα

Abstract

Palmitoleic acid (PMA) has anti-inflammatory and antidiabetic activities. Here we tested whether these effects of PMA on glucose homeostasis and liver inflammation, in mice fed with high-fat diet (HFD), are PPAR-α dependent. C57BL6 wild-type (WT) and PPAR-α-knockout (KO) mice fed with a standard diet (SD) or HFD for 12 weeks were treated after the 10th week with oleic acid (OLA, 300 mg/kg of b.w.) or PMA 300 mg/kg of b.w. Steatosis induced by HFD was associated with liver inflammation only in the KO mice, as shown by the increased hepatic levels of IL1-beta, IL-12, and TNF-α; however, the HFD increased the expression of TLR4 and decreased the expression of IL1-Ra in both genotypes. Treatment with palmitoleate markedly attenuated the insulin resistance induced by the HFD, increased glucose uptake and incorporation into muscle in vitro, reduced the serum levels of AST in WT mice, decreased the hepatic levels of IL1-beta and IL-12 in KO mice, reduced the expression of TLR-4 and increased the expression of IL-1Ra in WT mice, and reduced the phosphorylation of NF 𝜅B (p65) in the livers of KO mice. We conclude that palmitoleate attenuates diet-induced insulin resistance, liver inflammation, and damage through mechanisms that do not depend on PPAR-α.

Palmitoleate Reverses High Fat-induced Proinflammatory Macrophage Polarization via AMP-activated Protein Kinase (AMPK)

“…We also found that other monounsaturated fats, including trans-palmitoleate, are unable to antagonize palmitate-induced Nos2 expression, highlighting the specificity of cis-palmitoleate to offset palmitate-induced inflammation of BMDM. This result correlates with a recent observation that palmitoleate, but not oleate, can attenuate diet-induced glucose and insulin intolerance in mice (27).…”

“…A cluster of recent studies has revealed that, in vivo, adipose tissue secretes cis-palmitoleate (C16:1 n-7), a monounsaturated fatty acid that, in turn, protects against hepatic steatosis and improves whole-body insulin sensitivity (25)(26)(27). Moreover, the circulating levels of palmitoleate in humans strongly correlate with insulin action (28).…”

Nutritional approaches for managing obesity-associated metabolic diseases

“…For example, palmitoleate serves to reduce the liver inflammatory status in an animal model of HFD-induced insulin resistance seemingly by reducing NFκB signaling in macrophages (Guo et al 2012). Similar results have also recently been reported by Souza et al Specifically, palmitoleic acid supplementation in mice resulted in reduced liver proinflammatory cytokine production of IL-1β, IL-12, and TNFα, all of which was associated with reduced NFκB signaling and decreased TLR4 expression (Souza, et al 2014). …”

Flaxseed Oil or n‐7 Fatty Acid‐Enhanced Fish Oil Supplementation Alters Fatty Acid Composition, Plasma Insulin and Serum Ceramide Concentrations, and Gene Expression in Lambs

“…Chan et al () reported that palmitoleic acid can reverse the pro‐inflammatory cytokine expression in bone marrow‐derived macrophages from high‐fat fed mice and that these changes involved palmitoleic acid activation of AMP‐activated protein kinase ( AMPK ) signaling. Souza et al () also found that palmitoleic acid reversed the pro‐inflammatory effects and hepatic steatosis in mice fed high fat diets. Passo et al (2016) administered palmitoleic acid to lymphocytes and found that it reduced IL6 gene expression, whereas oleic acid did not.…”