Impaired skeletal muscle substrate oxidation in glucose-intolerant men improves after weight loss.
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
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 1H-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.


CONCLUSIONS
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.
Corpeleijn
Eva
E
Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands. E.Corpeleijn@hb.unimaas.nl
Mensink
Marco
M
Kooi
Marianne E
ME
Roekaerts
Paul M H J
PM
Saris
Wim H M
WH
Blaak
Ellen E
EE
D050260:Carbohydrate Metabolism / Q000502:physiology; D016022:Case-Control Studies; D004435:Eating / Q000502:physiology; D005215:Fasting / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism*; D005542:Forearm; D018149:Glucose Intolerance / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D010084:Oxidation-Reduction; D019518:Postprandial Period; D011236:Prediabetic State / Q000378:metabolism / Q000503:physiopathology; D014280:Triglycerides / Q000378:metabolism; D015431:Weight Loss / Q000502:physiology*
D005227:Fatty Acids; D014280:Triglycerides