Diabetologia

, Volume 61, Issue 2, pp 433–444 | Cite as

α-linolenic acid supplementation prevents exercise-induced improvements in white adipose tissue mitochondrial bioenergetics and whole-body glucose homeostasis in obese Zucker rats

  • Cynthia M.F. Monaco
  • Ross Proudfoot
  • Paula M. Miotto
  • Eric A.F. Herbst
  • Rebecca E.K. MacPherson
  • Graham P. Holloway
Article

Abstract

Aims/hypothesis

While the underlying mechanisms in the development of insulin resistance remain inconclusive, metabolic dysfunction in both white adipose tissue (WAT) and skeletal muscle have been implicated in the process. Therefore, we investigated the independent and combined effects of α-linolenic acid (ALA) supplementation and exercise training on whole-body glucose homeostasis and mitochondrial bioenergetics within the WAT and skeletal muscle of obese Zucker rats.

Methods

We randomly assigned obese Zucker rats to receive a control diet alone or supplemented with ALA and to remain sedentary or undergo exercise training for 4 weeks (CON-Sed, ALA-Sed, CON-Ex and ALA-Ex groups). Whole-body glucose tolerance was determined in response to a glucose load. Mitochondrial content and bioenergetics were examined in skeletal muscle and epididymal WAT (eWAT). Insulin sensitivity and cellular stress were assessed by western blot.

Results

Exercise training independently improved whole-body glucose tolerance as well as insulin-induced signalling in muscle and WAT. However, the consumption of ALA during exercise training prevented exercise-mediated improvements in whole-body glucose tolerance. ALA consumption did not influence exercise-induced adaptations within skeletal muscle, insulin sensitivity and mitochondrial bioenergetics. In contrast, within eWAT, ALA supplementation attenuated insulin signalling, decreased mitochondrial respiration and increased the fraction of electron leak to reactive oxygen species (ROS).

Conclusions/interpretation

These findings indicate that, in an obese rodent model, consumption of ALA attenuates the favourable adaptive changes of exercise training within eWAT, which consequently impacts whole-body glucose homeostasis. The direct translation to humans, however, remains to be determined.

Keywords

Exercise Glucose homeostasis Insulin signalling Mitochondria Obesity PUFA Respiration ROS Skeletal muscle WAT 

Abbreviations

ALA

α-linolenic acid

ANT

Adenosine nucleotide translocase

CON

Control (diet)

COXIV

Cytochrome c oxidase IV

DHA

Docosahexaenoic acid

DNP

2,4-Dinitrophenol

EPA

Eicosapentaenoic acid

ERK

Extracellular signalling-related kinase

eWAT

Epididymal white adipose tissue

Ex

Exercise (group)

4-HNE

trans-4-Hydroxy-2-nonenal

JNK

c-Jun N-terminal kinase

MCP1

Monocyte chemotactic protein 1

mtDNA

Mitochondrial DNA

OXPHOS

Mitochondrial oxidative phosphorylation

P-CoA

Palmitoyl-CoA

PDHE1α

Pyruvate dehydrogenase subunit E1-alpha

PmFbs

Permeabilised muscle fibres

PUFA

Polyunsaturated fatty acid

ROS

Reactive oxygen species

Sed

Sedentary (group)

WAT

White adipose tissue

Notes

Acknowledgements

We would like to thank D.C. Wright (Human Health & Nutritional Sciences, University of Guelph, Canada) for generously providing some of the antibodies used in this study.

Data availability

All relevant data are included in the article and/or the ESM files.

Funding

This work was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC, GPH, 03656). Infrastructure was purchased with assistance from the Canadian Foundation for Innovation/Ontario Research Fund (GPH, 25136). CMFM, PMM and EAFH were recipients of NSERC graduate scholarships.

Duality of interest

The authors declare that there is no duality of interest associated with this article.

Contribution statement

GPH designed the experiments. CMFM and GPH wrote the manuscript. CMFM, RP, PMM, EAFH and REKM performed experiments, and analysed and interpreted data. All authors edited the manuscript. All authors have approved the final version of the manuscript and agree to be accountable for all aspects of the work. All people designated as authors qualify for authorship, and all those who qualify for authorship are listed. CMFM is the guarantor of this work.

Supplementary material

125_2017_4456_MOESM1_ESM.pdf (1.3 mb)
ESM (PDF 1326 kb)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Cynthia M.F. Monaco
    • 1
  • Ross Proudfoot
    • 1
  • Paula M. Miotto
    • 1
  • Eric A.F. Herbst
    • 1
  • Rebecca E.K. MacPherson
    • 2
  • Graham P. Holloway
    • 1
  1. 1.Department of Human Health and Nutritional SciencesUniversity of GuelphGuelphCanada
  2. 2.Department of Health SciencesBrock UniversitySt CatharinesCanada

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