α-linolenic acid supplementation prevents exercise-induced improvements in white adipose tissue mitochondrial bioenergetics and whole-body glucose homeostasis in obese Zucker rats
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.
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.
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).
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.
KeywordsExercise Glucose homeostasis Insulin signalling Mitochondria Obesity PUFA Respiration ROS Skeletal muscle WAT
Adenosine nucleotide translocase
Cytochrome c oxidase IV
Extracellular signalling-related kinase
Epididymal white adipose tissue
c-Jun N-terminal kinase
Monocyte chemotactic protein 1
Mitochondrial oxidative phosphorylation
Pyruvate dehydrogenase subunit E1-alpha
Permeabilised muscle fibres
Polyunsaturated fatty acid
Reactive oxygen species
White adipose tissue
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.
All relevant data are included in the article and/or the ESM files.
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.
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.
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