Prevention of high-fat diet-induced muscular lipid accumulation in rats by α lipoic acid is not mediated by AMPK activation

Abstract

Obesity has reached epidemic proportions globally and the situation is likely to deteriorate further. It is well known that obesity predisposes individuals to a range of serious health complications with high morbidity rates including insulin resistance, type 2 diabetes mellitus, and cardiovascular diseases ( 1 ). The mechanisms underlying the progression from obesity to insulin resistance and, ultimately, type 2 diabetes are not fully elucidated ( 2 ). It is speculated that excessive FFA mobilization from adipose tissue leads to an increase in plasma FFA with ectopic deposition of triglycerides in muscle, the liver, and the pancreas as a result. The increased intramyocellular lipid (IMCL) content could disturb muscle insulin signaling, which ultimately results in muscle insulin resistance ( 3 ).Alpha lipoic acid (ALA), also known as thioctic acid, is a naturally occurring short-chain fatty acid with a powerful antioxidant capacity. It is synthesized in small amounts by plants and animals, including humans ( 4, 5 ). Endogenously synthesized ALA is an essential cofactor for several mitochondrial enzyme complexes that catalyze critical reactions related to energy production ( 6 ). ALA can also be exogenously derived from various food sources such as toAbstract Skeletal muscle triglyceride accumulation is associated with insulin resistance in obesity. Recently, it has been suggested that ␣ lipoic acid (ALA) improves insulin sensitivity by lowering triglyceride accumulation in nonadipose tissues via activation of skeletal muscle AMP-activated protein kinase (AMPK). We examined whether chronic ALA supplementation prevents muscular lipid accumulation that is associated with high-fat diets via activation of AMPK. In addition, we tested if ALA supplementation was able to improve insulin sensitivity in rats fed low-and high-fat diets (LFD, HFD). Supplementing male Wistar rats with 0.5% ALA for 8 weeks signifi cantly reduced body weight, both on LFD and HFD ( ؊ 24% LFD+ALA vs. LFD, P < 0.01, and ؊ 29% HFD+ALA vs. HFD, P < 0.001). Oil red O lipid staining revealed a 3-fold higher lipid content in skeletal muscle after HFD compared with LFD and ALA-supplemented groups ( P < 0.05). ALA improved whole body glucose tolerance ( ‫ف‬ 20% lower total area under the curve (AUC) in ALA supplemented groups vs. controls, P < 0.05). These effects were not mediated by increased muscular AMPK activation or ALA-induced improvement of muscular insulin sensitivity. To conclude, the prevention of HFD-induced muscular lipid accumulation and the improved whole body glucose tolerance are likely secondary effects due to the anorexic nature of ALA. -Timmers, S., J. Abbreviations: ACC, acetyl-CoA carboxylase; ALA, ␣ lipoic acid; AMPK, AMP-activated protein kinase; AUC, area under the curve; % E, % energy; HFD, high-fat diet; IMCL, intramyocellular lipid; IpGTT, intraperitoneal glucose tolerance test; LFD, low-fat diet; OLETF, Otsuka Long Evans Tokushima Fatty.

Alpha-lipoic acid attenuates insulin resistance and improves glucose metabolism in high fat diet-fed mice

“…In the present study, the main purpose was to investigate whether ALA plays a key role in glucose metabolism in HFD-induced NAFLD mice models. Several studies have been performed with the aim of demonstrating that ALA regulates whole-body glucose and glucose uptake and improves tolerance test performance [24,25] . We demonstrated that ALA had the same metabolic action upon the mice, such as improved body composition, glucose and insulin tolerance.…”

High-fat feeding does not induce an autophagic or apoptotic phenotype in female rat skeletal muscle

“…Additionally, despite evidence that some physiological responses to HF feeding are sex-dependent, [20][21][22] much of the current literature has been conducted using male animals. 10,[23][24][25][26][27][28][29][30][31][32] Recently, calls to eliminate gender bias in animal research have been made; 33,34 making an examination of the muscle-specific adaptations to HF feeding in a female model timely. Therefore, the purpose of this study was to examine morphological, apoptotic, and autophagic responses to HF feeding in both predominantly type I (oxidative) and type II (glycolytic) muscles of female rats.…”

Lipoic acid inhibits leptin secretion and Sp1 activity in adipocytes

“…Thus, LA can be considered as a promising therapeutic approach for chronic inflammatory diseases such as diabetes and obesity [12,13]. Thus, it has been reported the ability of LA to reduced body weight gain in rodents by suppressing food intake and increasing energy expenditure [8,[14][15][16]. Studies of our group has also described that LA decreased feed efficiency and intestinal sugar transport, which could explain at least in part its reducing effects on body weight gain despite of high fat diet feeding [14].…”