Alpha-linolenic acid supplementation and exercise training reveal independent and additive responses on hepatic lipid accumulation in obese rat.

Key Findings

Obesity is a very strong risk factor for the development of hepatic insulin resistance, a situation

that directly impairs whole body glucose homeostasis.  Strategies that are able to prevent lipid accumulation may help maintain hepatic insulin sensitivity, and in turn, combat the increasing health burden associated with obesity.  With a combined ALA-Ex intervention, animals displayed increases in mitochondrial, MTTP, and apolipoprotein B100 protein contents, and the greatest improvements in lipid profiles and PL content. Overall, while exercise alone promoted subtle improvements in hepatic PL content and reductions in lipid accumulation, ALA-Ex enhanced this response. This is possibly through a combination of increased fatty acid oxidation and lipid secretion. The findings demonstrate that combined ALA and exercise training yield an additive effect on hepatic lipid accumulation but not insulin signaling in obese rodents. This may be due to the combined effects of ALA and exercise on mitochondrial content, MTTP/ apolipoprotein B100 expression, and total PL content. Longer exposure to the combined intervention would reveal these improvements, and intensity of exercise should be looked at. The data suggest interventions that target lipid PL contents could confer benefits on hepatic lipid metabolism in obese rodents, and this may be linked with improvements in mitochondrial capacity and lipid secretion to support reduced lipid storage and insulin sensitivity.

ABSTRACT

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.