Palmitoleic Acid Improves Metabolic Functions in Fatty Liver by PPARα-Dependent AMPK Activation

J Cell Physiol. 2017 Aug;232(8):2168-2177. doi: 10.1002/jcp.25715. Epub 2017 Mar 24.

Abstract

Background: Palmitoleic acid, since described as lipokine, increases glucose uptake by modulation of 5'AMP-activated protein kinase (AMPK), as well as increasing lipolysis by activation of peroxisome proliferator-activated receptor-α (PPARα), in adipose tissue. However, in liver, the effects of palmitoleic acid on glucose metabolism and the role of PPARα remain unknown.

Objective: To investigate whether palmitoleic acid improved the hepatic insulin sensitivity of obese mice.

Methods: C57BL6 and PPARα knockout (KO) mice were fed for 12 weeks with a standard diet (SD) or high-fat diet (HF), and in the last 2 weeks were treated with oleic or palmitoleic acid.

Results: Palmitoleic acid promoted a faster uptake of glucose in the body, associated with higher insulin concentration; however, even when stimulated with insulin, palmitoleic acid did not modulate the insulin pathway (AKT, IRS). Palmitoleic acid increased the phosphorylation of AMPK, upregulated glucokinase and downregulated SREBP-1. Regarding AMPK downstream, palmitoleic acid increased the production of FGF-21 and stimulated the expression of PPARα. Palmitoleic acid treatment did not increase AMPK phosphorylation, modulate glucokinase or increase FGF-21 in liver of PPARα KO mice.

Conclusions: In mice fed with a high-fat diet, palmitoleic acid supplementation stimulated the uptake of glucose in liver through activation of AMPK and FGF-21, dependent on PPARα. J. Cell. Physiol. 232: 2168-2177, 2017. © 2016 Wiley Periodicals, Inc.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Diet, High-Fat
  • Disease Models, Animal
  • Energy Metabolism / drug effects*
  • Enzyme Activation
  • Fatty Acids, Monounsaturated / pharmacology*
  • Fatty Liver / drug therapy*
  • Fatty Liver / enzymology
  • Fatty Liver / genetics
  • Fatty Liver / pathology
  • Fibroblast Growth Factors / metabolism
  • Genetic Predisposition to Disease
  • Glucokinase / metabolism
  • Glucose / metabolism
  • Hypoglycemic Agents / pharmacology
  • Insulin / pharmacology
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / pathology
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • PPAR alpha / deficiency
  • PPAR alpha / genetics
  • PPAR alpha / metabolism*
  • Phenotype
  • Phosphorylation
  • Signal Transduction / drug effects
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Time Factors

Substances

  • Fatty Acids, Monounsaturated
  • Hypoglycemic Agents
  • Insulin
  • PPAR alpha
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • fibroblast growth factor 21
  • palmitoleic acid
  • Fibroblast Growth Factors
  • Glucokinase
  • AMP-Activated Protein Kinases
  • Glucose