Exercise-induced, but not creatine-induced, decrease in intramyocellular lipid content improves insulin sensitivity in rats

The effect of creatine supplementation, alone or in combination with exercise training, on insulin sensitivity, intramyocellular lipid content (IMCL) and fatty acid translocase (FAT)/CD36 content was investigated in rats fed a sucrose-rich cafeteria diet during 12 weeks. Five experimental conditions were CON, receiving normal pellets; CAF, fed the cafeteria diet; CAF_TR, fed the cafeteria diet together with exercise training in weeks 8-12 and CAF_CR and CAF_CRT that were analogous to CAF and CAF_TR, respectively, but which received daily 2.5% of creatine monohydrate. During intravenous glucose tolerance test, compared with CON, whole-body glucose tolerance was reduced in CAF and CAF_CR but not in CAF_TR and CAF_CRT. Insulin-stimulated glucose transport in perfused red gastrocnemius muscles was impaired in CAF and CAF_CR but not in the trained groups. IMCL content in soleus and extensor digitorum longus muscles was higher in CAF than in CON, but not in CAF_TR, CAF_CR and CAF_CRT. Compared with CON and CAF, FAT/CD36 protein content in m. soleus, was ∼40% lower in CAF_CR, CAF_TR and CAF_CRT. The fraction of fecal fat, as determined in a 3-week post hoc study, was 25% higher in CAF_CR than in CON. Moreover, in CAF_CR, triglyceride concentration in blood and liver were significantly lower than in CAF. It is concluded that creatine supplementation in rats on a cafeteria diet inhibits IMCL accumulation via inhibition of gastrointestinal lipid absorption together with lower muscle FAT/CD36 content. Furthermore, exercise-induced but not creatine-induced reduction of IMCL is associated with improved insulin action on glucose transport in muscle cells.