Palmitoleic acid (n-7) attenuates the immunometabolic disturbances caused by a high-fat diet independently of PPARα.

Camila O Souza,Isabella T Mota,José C Rosa Neto,Lara M Gomes,Milena Carvalho-Silva,Helena A P Batatinha,Sandro M Hirabara,Emilio L Streck,Alexandre A S Teixeira,Edson A Lima

doi:10.1155/2014/582197

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.

Highlights

Chronic positive energy balance through inadequate dietary habits and a sedentary life style leads to an excessive accumulation of body fat, known as obesity, the prevalence of which is increasing alarmingly worldwide [1]
Treatment with palmitoleic acid (PMA) did not alter the body weight, the weights of the white and brown adipose tissues, or the plasma lipid profile of either group, but treatment with palmitoleic acid reduced the fasting glucose levels in both WT and KO mice that were subjected to the high-fat diet (HFD) (Table 2)
WT mice fed with standard diet (SD) or C57 and Peroxisome proliferator activated receptor α (PPARα)-knockout (KO) mice fed with a high-fat diet and treated with oleic acid (HFD) or palmitoleic acid (HFD Palmitoleic acid (PMA))

Summary

Introduction

Chronic positive energy balance through inadequate dietary habits and a sedentary life style leads to an excessive accumulation of body fat, known as obesity, the prevalence of which is increasing alarmingly worldwide [1]. Obese individuals have a greater risk for the development of many chronic and highly incident diseases such as type 2 diabetes, dislipidemia, hepatic steatosis, and some types of cancer [2,3,4,5,6]. Among these diseases, nonalcoholic fatty liver disease (NAFLD), which is defined as excessive hepatic lipid accumulation, is one of the most common comorbidities associated with obesity and insulin resistance. Strategies to counteract hepatic steatosis, inflammation, Mediators of Inflammation and increased hepatic glucose production are crucial to the prevention and treatment of chronic metabolic diseases

Methods

Results

Conclusion