Effect of Exercise and Calorie Restriction on Tissue Acylcarnitines, Tissue Desaturase Indices, and Fat Accumulation in Diet-Induced Obese Rats

Abstract

Both exercise and calorie restriction interventions have been recommended for inducing weight-loss in obese states. However, there is conflicting evidence on their relative benefits for metabolic health and insulin sensitivity. This study seeks to evaluate the differential effects of the two interventions on fat mobilization, fat metabolism, and insulin sensitivity in diet-induced obese animal models. After 4 months of ad libitum high fat diet feeding, 35 male Fischer F344 rats were grouped (n = 7 per cohort) into sedentary control (CON), exercise once a day (EX1), exercise twice a day (EX2), 15% calorie restriction (CR1) and 30% calorie restriction (CR2) cohorts. Interventions were carried out over a 4-week period. We found elevated hepatic and muscle long chain acylcarnitines with both exercise and calorie restriction, and a positive association between hepatic long chain acylcarnitines and insulin sensitivity in the pooled cohort. Our result suggests that long chain acylcarnitines may not indicate incomplete fat oxidation in weight loss interventions. Calorie restriction was found to be more effective than exercise in reducing body weight. Exercise, on the other hand, was more effective in reducing adipose depots and muscle triglycerides, favorably altering muscle/liver desaturase activity and improving insulin sensitivity.

CR reprograms acetyl‐CoA metabolism and induces long‐chain acyl‐CoA dehydrogenase and CrAT expression

“…Data on protein acetylation under CR from our study and two other studies (Sato et al, 2017; Schwer et al, 2009) are in line with the increase in acetyl‐CoA in CR liver. Gopalan et al also reported an induction for a few long‐chain acylcarnitines; however, the effect was significant for 15% CR but not 30% CR (Gopalan et al, 2016). To the best of our knowledge, the effect of CR on acylcarnitine profile in healthy animals has not been reported.…”

Novel Markers of the Metabolic Impact of Exogenous Retinoic Acid with A Focus on Acylcarnitines and Amino Acids

“…The pathophysiological significance of ACs is complex, since, as stated in the Introduction, increased levels in plasma and tissues are observed in obesity and insulin resistant state [25,26,27,28,29], but also after weight loss and exercise [30,31,32]. It appears that, depending on the conditions, excess ACs may inflict insulin resistance or simply reflect FAO rates in tissues [24].…”

“…Further, AC synthesis and efflux from mitochondria serves physiological functions in the modulation of cellular metabolism, as it helps avoiding both the sequestration of mitochondrial CoA in the form of acyl-CoAs and the feed-back inhibition of the pyruvate dehydrogenase complex (and hence of glucose oxidation) by excess mitochondrial acetyl-CoA [24,51]. Interestingly, increments in long-chain AC levels found under conditions of obesity, high-fat diet, or lipid stress take place in parallel with decreased tissue and plasma levels of free carnitine [52,53], whereas increments of AC levels found under conditions of weight loss or exercise take place in parallel with increases in the tissue/ plasma levels of free carnitine [30,32]. In fact, carnitine insufficiency is a common feature of insulin-resistant states such as advanced age and diet-induced obesity in rodents [54].…”

“…Plasma AC levels have attracted attention as markers of obesity-associated metabolic disturbances such as insulin resistance, yet this relationship is complex [24]. Increased levels of long-chain ACs in plasma and tissues have been described in association with obesity and insulin resistance [25,26,27,28,29], but also after weight loss and exercise paralleling increases in systemic insulin sensitivity [30,31,32]. Similar to ACs, AAs such as branched-chain AAs and aromatic AAs have been proposed as potential markers for obesity-related metabolic disturbances on the basis of metabolomics studies [33,34].…”

Human thermogenic adipocytes: a reflection on types of adipocyte, developmental origin, and potential application

“…Thus, controlling these factors could effect on the development of obesity and longevity. Several evidence indicates that caloric restriction (CR) can reduce bodyweight (Das et al 2017;Gopalan et al 2016) and enhance longevity (Holloszy and Fontana 2007;Lane et al 1997;Martin-Montalvo et al 2013;Mattison et al 2017;Ravussin et al 2015;Verdery et al 1997). In monkeys, a 30% reduction of caloric intake leads to a significantly elevated level of a good cholesterol (HDL 2B) and a decreased level of triglyceride which further reduce risk for agingrelated disorders such as cardiovascular disease (Verdery et al 1997).…”