ABSTRACT
OBJECTIVE: To investigate substrate metabolism during exercise in an adult with lipin-1 deficiency, an inherited defect in lipid homeostasis, and to study the effect of glucose supplementation on his exercise tolerance. METHODS: We studied a 48-year-old man with lipin-1 deficiency and 2 healthy men. The patient has exercise intolerance and monthly episodes of rhabdomyolysis. All participants performed a submaximal exercise test while total fatty acid oxidation (FAO) and palmitate oxidation rate were assessed by stable isotope technique and indirect calorimetry. On another day, the patient was infused with 10% glucose (410 mL/h) and repeated the exercise. On the third and fourth visits, he was randomized in a double-blind manner to drink a supplement of glucose (soft drink 2% concentration) or placebo (soft drink: aspartame, acesulfame-K) before and during exercise. RESULTS: Mean FAO and palmitate oxidation rate during exercise were lower in the patient vs controls: 431 vs 1,271 and 1912 µmol/min and 122 vs 191 and 212 µmol/min. Plasma fatty acid concentration was lower in the patient during exercise than in controls: 477 vs 643 and 630 µmol/L. The patient's exercise duration increased from 36 to 60 minutes with IV glucose and 46 minutes with oral glucose, and his rating of exertion dropped from 15 to 9 on average (Borg scale). CONCLUSION: In this adult lipin-1-deficient patient, FAO was reduced, which was associated with no increase in plasma free fatty acids during submaximal exercise, and his exercise capacity improved with continuous ingestion of high-dose glucose. CLINICALTRIALSGOV IDENTIFIER: NCT02635269.