Polyunsaturated Fatty Acids Attenuate Diet Induced Obesity and Insulin Resistance, Modulating Mitochondrial Respiratory Uncoupling in Rat Skeletal Muscle

PLoS One. 2016 Feb 22;11(2):e0149033. doi: 10.1371/journal.pone.0149033. eCollection 2016.


Objectives: Omega (ω)-3 polyunsaturated fatty acids (PUFA) are dietary compounds able to attenuate insulin resistance. Anyway, the precise actions of ω-3PUFAs in skeletal muscle are overlooked. We hypothesized that PUFAs, modulating mitochondrial function and efficiency, would ameliorate pro-inflammatory and pro-oxidant signs of nutritionally induced obesity.

Study design: To this aim, rats were fed a control diet (CD) or isocaloric high fat diets containing either ω-3 PUFA (FD) or lard (LD) for 6 weeks.

Results: FD rats showed lower weight, lipid gain and energy efficiency compared to LD-fed animals, showing higher energy expenditure and O2 consumption/CO2 production. Serum lipid profile and pro-inflammatory parameters in FD-fed animals were reduced compared to LD. Accordingly, FD rats exhibited a higher glucose tolerance revealed by an improved glucose and insulin tolerance tests compared to LD, accompanied by a restoration of insulin signalling in skeletal muscle. PUFAs increased lipid oxidation and reduced energy efficiency in subsarcolemmal mitochondria, and increase AMPK activation, reducing both endoplasmic reticulum and oxidative stress. Increased mitochondrial respiration was related to an increased mitochondriogenesis in FD skeletal muscle, as shown by the increase in PGC1-α and -β.

Conclusions: our data strengthened the association of high dietary ω3-PUFA intake with reduced mitochondrial energy efficiency in the skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dietary Fats / adverse effects*
  • Dietary Fats / pharmacology
  • Endoplasmic Reticulum Stress / drug effects
  • Fatty Acids, Omega-3 / pharmacology*
  • Male
  • Mitochondria, Muscle / metabolism*
  • Muscle, Skeletal / metabolism*
  • Obesity / chemically induced
  • Obesity / metabolism*
  • Oxidative Stress / drug effects
  • Oxygen Consumption / drug effects*
  • Rats
  • Rats, Wistar


  • Dietary Fats
  • Fatty Acids, Omega-3

Grant support

This work was supported by the University of Naples Federico II, grant number COAN CA0440050101. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.