The Effects of Long‐ or Medium‐Chain Fat Diets on Glucose Tolerance and Myocellular Content of Lipid Intermediates in Rats

Abstract

Accumulation of triacylglycerols (TAGs) and acylcarnitines in skeletal muscle upon high-fat (HF) feeding is the resultant of fatty acid uptake and oxidation and is associated with insulin resistance. As medium-chain fatty acids (MCFAs) are preferentially β-oxidized over long-chain fatty acids, we examined the effects of medium-chain TAGs (MCTs) and long-chain TAGs (LCTs) on muscle lipid storage and whole-body glucose tolerance. Rats fed a low-fat (LF), HFLCT, or an isocaloric HFMCT diet displayed a similar body weight gain over 8 weeks of treatment. Only HFLCT increased myocellular TAG (42.3 ± 4.9, 71.9 ± 6.7, and 48.5 ± 6.5 µmol/g for LF, HFLCT, and HFMCT, respectively, P < 0.05) and long-chain acylcarnitine content (P < 0.05). Neither HF diet increased myocellular diacylglycerol (DAG) content. Intraperitoneal (IP) glucose tolerance tests (1.5 g/kg) revealed a significantly decreased glucose tolerance in the HFMCT compared to the HFLCT-fed rats (802 ± 40, 772 ± 18, and 886 ± 18 area under the curve for LF, HFLCT, and HFMCT, respectively, P < 0.05). Finally, no differences in myocellular insulin signaling after bolus insulin injection (10 U/kg) were observed between LF, HFLCT, or HFMCT-fed rats. These results show that accumulation of TAGs and acylcarnitines in skeletal muscle in the absence of body weight gain do not impede myocellular insulin signaling or whole-body glucose intolerance.

Capric Acid Up-Regulates UCP3 Expression without PDK4 Induction in Mouse C2C12 Myotubes

“…However, several lines of investigation reported that MCFA-rich diets increased MCFA concentrations in the blood as well as several target organs including the skeletal muscle of rodents (8,24,25). The present study also showed that capric acid directly regulated UCP3 expression in skeletal muscle cells by an in vitro approach.…”

Long- and Medium-Chain Fatty Acids Induce Insulin Resistance to a Similar Extent in Humans Despite Marked Differences in Muscle Fat Accumulation

“…Despite this reduction in whole-body insulin sensitivity, however, Turner et al (11) observed beneficial effects of the high-fat MCT diet on muscle fat accumulation and muscle insulin sensitivity, whereas liver insulin sensitivity was in fact similarly reduced upon both the MCT and the LCT diet. However, we have previously shown that 8 wk of highfat MCT vs. high-fat LCT feeding in mice resulted in a similar reduction in whole-body insulin resistance, despite dramatically lower lipid levels in both liver and skeletal muscle after the high-fat MCT diet (9). Intriguingly, and in contrast to the previously mentioned study by Turner et al (11), the reduction in whole-body insulin sensitivity upon the high-fat MCT diet was mainly accounted for by a reduced peripheral glucose uptake (primarily skeletal muscle), whereas liver insulin sensitivity appeared normal (9).…”

“…However, we have previously shown that 8 wk of highfat MCT vs. high-fat LCT feeding in mice resulted in a similar reduction in whole-body insulin resistance, despite dramatically lower lipid levels in both liver and skeletal muscle after the high-fat MCT diet (9). Intriguingly, and in contrast to the previously mentioned study by Turner et al (11), the reduction in whole-body insulin sensitivity upon the high-fat MCT diet was mainly accounted for by a reduced peripheral glucose uptake (primarily skeletal muscle), whereas liver insulin sensitivity appeared normal (9). The discrepancy in results between these two animal studies might be explained by the specific type of MCFA used in the respective studies; whereas the diets used by Turner et al (11) primarily contained fatty acids of 12 and 14 carbon atoms in chain length, we previously used fatty acids of shorter chain length (C8 and C10).…”

“…This may result in blunted lipid-induced insulin resistance upon MCFA administration. Indeed, we have recently shown that consumption of a high-fat diet rich in medium-chain triacylglycerols (MCT), as opposed to long-chain triacylglycerols (LCT), does not lead to ectopic fat accumulation in skeletal muscle and liver of both rats and mice (9,10). However, we were unable to show beneficial effects of the reduction in intramyocellular lipid levels upon high-fat MCT feeding in mice with respect to insulin-stimulated glucose uptake in the peripheral organs (primarily accounted for by skeletal muscle) (10).…”

Acylcarnitines activate proinflammatory signaling pathways

“…Yet, the in situ free concentrations of many metabolites, including acylcarnitines, are difficult to determine in tissues, and it is important to note that in our cell models acylcarnitines were applied in the culture media. With a rodent obesity models, muscle mediumchain fatty acid (MCFA) C14-carnitine moieties reach estimated concentrations of 5-10 M, with some LCFA-carnitine concentrations around 5-10 times higher (calculated from (3,7)). Furthermore, the total tissue concentrations of several acylcarnitines of longer chain length in mice were shown to be much greater than that of L-C14 carnitine used in our study (15).…”