α-Linolenic acid supplementation and exercise training reveal independent and additive responses on hepatic lipid accumulation in obese rats

Abstract

α-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 wk (C-Sed, ALA-Sed, C-Ex, and ALA-Ex). ALA-Sed rats had increased microsomal-triglyceride transfer protein (MTTP), a protein required for lipoprotein assembly/secretion, as well as modestly increased PL 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 triacylglyceride, 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.

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

“…The effects of ALA and exercise on glucose homeostasis and insulin sensitivity In the present study, whole-body glucose tolerance was improved following exercise training, and, unexpectedly, ALA supplementation independently or in combination with exercise training did not improve glucose tolerance. These findings are in stark contrast to our previous reports, which have shown that whole-body glucose tolerance is improved in obese Zucker rats following a diet supplemented with ALA [39,40]. The main difference between the present study and our previous reports showing a beneficial response in glucose homeostasis following consumption of n-3 PUFAs is the length of time consuming the PUFA fortified diets.…”

“…The main difference between the present study and our previous reports showing a beneficial response in glucose homeostasis following consumption of n-3 PUFAs is the length of time consuming the PUFA fortified diets. Specifically, in the present study animals consumed a diet high in ALA for 4 weeks, while in previous studies animals were supplemented for 12 weeks [39,40]. In humans, a previous report also showed that diets enriched in n-3 PUFAs take~4 weeks to alter the lipid composition of muscle [48] and therefore it is likely that a slightly longer duration of dietary consumption would have resulted in a beneficial response to the independent intake of ALA.…”

“…Mitochondrial H 2 O 2 emission and oxidative stress in skeletal muscle ALA supplementation for 12 weeks has been previously shown to increase mitochondrial H 2 O 2 emission in obese Zucker rats [40]. Given that mitochondrial-derived ROS have been linked to insulin resistance [46], we examined mitochondrial H 2 O 2 emission rates in the presence and absence of a submaximal ADP concentration.…”

“…Body weight was measured every week, while glucose tolerance tests were performed 48 h before animals were anaesthetised with isoflurane (4% in O 2 ) to conduct experiments described below. We have previously reported on the effects of these interventions with respect to cardiovascular function and hepatic lipid content [40,41]. Experimenters were not blind to group assignment during the conduction of experiments and all experiments were conducted in accordance with protocols approved by the University of Guelph Animal Care Committee.…”

Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice

“…Quercetin has also been shown to promote lipolysis in the livers of NAFLD mice. α-Linolenic acid-rich flaxseed oil also increases lipolysis through enhanced ATGL expression, preventing alcoholic hepatic steatosis in mice [16]. Ginsenoside Rb2 also suppresses lipid accumulation in the liver by upregulating ATGL and phosphorylation of HSL in obese mice [52].…”