Alpha-linolenic acid (ALA) supplementation or exercise training can independently prevent hepatic lipid accumulation and reduced insulin signaling, however, this may occur through different mechanisms-of-action. In the current study, obese Zucker rats displayed decreased phospholipid (PL) content in association with hepatic lipid abundance, and therefore, we examined whether ALA and exercise training would prevent these abnormalities differently to reveal additive effects on the liver. To achieve this aim, obese Zucker rats were fed control diet alone or supplemented with ALA, and were sedentary or exercise trained for 4 weeks (C-Sed, ALA-Sed, C-Ex, ALA-Ex). ALA-Sed rats had increased microsomal-triglyceride transfer protein (MTTP), a protein required for lipoprotein assembly/secretion, as well as modestly increased phospholipid content in the absence of improvements in mitochondrial content, lipid accumulation, or insulin sensitivity. In contrast, C-Ex rats had increased mitochondrial content and insulin sensitivity, however, this corresponded with minimal improvements in PL content and hepatic lipid accumulation. Importantly, ALA-Ex rats demonstrated additive improvements in PL content and hepatic steatosis, which corresponded with increased mitochondrial content, MTTP and apolipoprotein B100 content, greater serum TAG, and insulin sensitivity. Overall, these data demonstrate additive effects of ALA and exercise training on hepatic lipid accumulation, as exercise-training preferentially increased mitochondrial content, while ALA promoted an environment conducive for lipid secretion. These data highlight the potential for combination therapy to mitigate liver disease progression.
- hepatic lipid accumulation
- mitochondrial capacity
- lipid secretion
- Copyright © 2017, American Journal of Physiology-Endocrinology and Metabolism