Impaired Skeletal Muscle Substrate Oxidation in Glucose‐intolerant Men Improves After Weight Loss

Abstract

objective: An impaired fatty acid handling in skeletal muscle may be involved in the development of insulin resistance and diabetes mellitus type 2 (DM2). We investigated muscle fatty acid metabolism in glucose-intolerant men (impaired glucose tolerance (IGT)), a prediabetic state, relative to BMI-matched control men (normal glucose tolerance (NGT)) during fasting and after a meal, because most people in the western society are in the fed state most of the day. Methods and Procedures: Skeletal muscle free fatty acid (FFA) uptake and oxidation were studied using the stable isotope tracer [2,2-2 H]-palmitate and muscle indirect calorimetry in the forearm model during fasting and after a mixed meal (33 energy % (E%) carbohydrates, 61 E% fat). Intramyocellular triglycerides (IMTGs) were monitored with 1 H-magnetic resonance spectroscopy. IGT men were re-examined after weight loss (−15% of body weight (BW)). Results: The postprandial increase in forearm muscle respiratory quotient (RQ) was blunted in IGT compared to NGT, but improved after weight loss. Weight loss also improved fasting-fat oxidation and tended to decrease IMTGs (P = 0.08). No differences were found in fasting and postprandial forearm muscle fatty acid uptake between NGT and IGT, or in IGT before and after weight loss. Discussion: The ability to switch from fat oxidation to carbohydrate oxidation after a meal is already impaired in the prediabetic state, suggesting this may be an early factor in the development toward DM2. This impaired ability to regulate fat oxidation during fasting and after a meal (impaired metabolic flexibility) can be (partly) reversed by weight loss.

Synergistic induction of lipid catabolism and anti-inflammatory lipids in white fat of dietary obese mice in response to calorie restriction and n-3 fatty acids

“…ALA, α-linolenic acid (18:3 n-3); DGLA, dihomo-γ-linolenic acid (20:3 n-6); EFOX, electrophilic oxoderivatives from DHA [19]; GLA, γ-linolenic acid (18:3 n-6); HXB3, hepoxilin B3; LA, linoleic acid (18:2 n-6); response of plasma levels of NEFA and glucose to FASTED to RE-FED transition and the glucose-induced increase in RQ. This improvement of metabolic flexibility correlated with changes in body weight, adiposity and glycaemic control in accordance with the notion that metabolic flexibility is closely associated with insulin sensitivity [2,32] and that impaired flexibility represents an early defect in the development of type 2 diabetes [35]. Metabolic syndrome is linked to inflammatory changes in both WAT and liver [1].…”

Thujone, a component of medicinal herbs, rescues palmitate-induced insulin resistance in skeletal muscle

“…Many studies (3,4,19,28,34) have found a positive association between the increase in palmitate oxidation and insulin-stimulated glucose transport. In the present study, a similar association appeared to be present, as the palmitate-induced reduction and the thujonestimulated rescue of insulin-stimulated glucose transport were accompanied by concurrent changes in fatty acid oxidation.…”

Measurement and Physiological Relevance of the Maximal Lipid Oxidation Rate During Exercise (LIPOXmax)

“…However, there is a rationale to do so, as largely described above. Multiple studies have show that fatty acid handling and oxidation is impaired in skeletal muscle of obese, impaired glucose-tolerant, and T2D individuals (Blaak, 2004;Corpeleijn et al, 2008Corpeleijn et al, , 2009Kelley et al, 1999;Mensink et al, 2001). This defect leads to propose exercise protocols aiming at restoring muscular ability to oxidize lipids.…”