Although there are many aspects that are still needed to be identified between the link of lipotoxicity and insulin resistance, it is well known that an increase in intracellular lipid levels leads to a decrease in insulin action [8, 16, 31]. If this is secondary to an excess of plasma free fatty acids and/or a decrease in their beta-oxidation is unclear [32]. This last defect in Foretinib patients with type 2 DM and obesity has been shown
to persist in the fasting state and is not removed after an insulin stimulus with a euglycemic clamp [33, 34]. This disorder, also see more known as metabolic inflexibility, has been attributed to inhibition of CPT1 by malonyl-CoA leading to an inability to transport long-chain AC check details into the mitochondrial matrix and thus the dysfunction in beta-oxidation [21]. In our study, the identification of similar levels of
free fatty acids at baseline as well as at the end of the intervention, suggests that beta-oxidation was improved, being partially reversed, likely due to an increase in CPT1 function, since a decrease in long-chain AC (C14 and C18) occurred only in the case group as a result of the AE program. This conclusion is strengthened by the fact that pairs of long chain ACs (C14 and C18) were those that were modified; the ACs pairs of up to 20 carbons accumulate in response to deterioration in beta-oxidation of fatty acids in contrast with the accumulation of odd ACs that result from the catabolism of amino acids, except for C4, which is derived from both processes [22].
It is important to point out that the baseline AC pattern was similar Aprepitant in both groups and agrees with that reported previously [22]. When interpreting the mechanism of decline in long-chain AC in the group of cases at the end of the study, it is necessary to analyze the influence of a change in caloric intake and a resulting decrease in body weight. The influence of these on beta-oxidation has also been an area of controversy [35, 36]. In our study, both groups of participants were carefully instructed not to alter their caloric intake throughout the 10-week study. Consequently, any changes in body weight should be a consequence of the exercise program. Only the case group showed a significant weight loss at the end of the exercise program, which should be attributed to their better adherence and intensity to the AE program. In accordance with this concept is the fact that free fatty acid levels remained unchanged in both groups during the study. The favorable change in body weight and anthropometry only due to weight loss without exercise should not be regarded as the critical mechanism of metabolic flexibility recovery. Goodpasture et al.