Van Proeyen K, Szlufcik K, Nielens H, Deldicque L, Van Dyck R, Ramaekers M, Hespel P. High-fat diet overrules the effects of training on fiber-specific intramyocellular lipid utilization during exercise. J Appl Physiol 111: 108 -116, 2011. First published May 5, 2011 doi:10.1152/japplphysiol.01459.2010In this study, we compared the effects of endurance training in the fasted state (F) vs. the fed state [ample carbohydrate intake (CHO)] on exercise-induced intramyocellular lipid (IMCL) and glycogen utilization during a 6-wk period of a hypercaloric (ϳϩ30% kcal/day) fat-rich diet (HFD; 50% of kcal). Healthy male volunteers (18 -25 yrs) received a HFD in conjunction with endurance training (four times, 60 -90 min/wk) either in F (n ϭ 10) or with CHO before and during exercise sessions (n ϭ 10). The control group (n ϭ 7) received a HFD without training and increased body weight by ϳ3 kg (P Ͻ 0.001). Before and after a HFD, the subjects performed a 2-h constant-load bicycle exercise test in F at ϳ70% maximal oxygen uptake rate. A HFD, both in the absence (F) or presence (CHO) of training, elevated basal IMCL content by ϳ50% in type I and by ϳ75% in type IIa fibers (P Ͻ 0.05). Independent of training in F or CHO, a HFD, as such, stimulated exercise-induced net IMCL breakdown by approximately twofold in type I and by approximately fourfold in type IIa fibers. Furthermore, exercise-induced net muscle glycogen breakdown was not significantly affected by a HFD. It is concluded that a HFD stimulates net IMCL degradation by increasing basal IMCL content during exercise in type I and especially IIa fibers. Furthermore, a hypercaloric HFD provides adequate amounts of carbohydrates to maintain high muscle glycogen content during training and does not impair exercise-induced muscle glycogen breakdown. skeletal muscle; fasted exercise; fat-rich feeding; energy substrate metabolism; muscle lipids IT IS WELL ESTABLISHED THAT dietary factors play an important role in modulating the acute and chronic metabolic responses to endurance exercise (30). In this regard, increased preexercise dietary fat supply stimulates energy provision via fat oxidation during exercise (8,33). By analogy, fatty acid infusion elevates the input of free fatty acids (FFAs) in the energy substrate mix fueling muscle contractions (22, 48a, 49). Furthermore, chronic exposure to a high-fat diet (HFD) also enhances the use of FFAs in endurance exercise (8,9,25,29,(32)(33)(34)58). This is, at least partly, due to upregulation of rate-limiting steps in fat metabolic pathways. Thus FFA oxidation can be stimulated with appropriate chronic exercise and/or nutrition (e.g., HFD), which upregulates pivotal steps in FFA catabolism such as fatty acid translocase (FAT)/CD36 (4, 9), -hydroxyacyl CoA dehydrogenase (-HAD) (9, 31), and hormone-sensitive lipase (HSL) (58). However, it is still unclear whether these adaptations are specifically due to the increased FFA supply per se or result from decreased glucose availability. Omission of glucose ingestion during exercise a...