PT  - JOURNAL ARTICLE
AU  - Raaschou-Pedersen, Daniel
AU  - Madsen, Karen L.
AU  - Stemmerik, Mads G.
AU  - Eisum, Anne-Sofie V.
AU  - Straub, Volker
AU  - Vissing, John
TI  - Fat oxidation is impaired during exercise in lipin-1 deficiency
AID  - 10.1212/WNL.0000000000008240
DP  - 2019 Oct 08
TA  - Neurology
PG  - e1433--e1438
VI  - 93
IP  - 15
4099  - http://n.neurology.org/content/93/15/e1433.short
4100  - http://n.neurology.org/content/93/15/e1433.full
SO  - Neurology2019 Oct 08; 93
AB  - 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.ClinicalTrials.gov identifier NCT02635269.CHO=carbohydrate oxidation; CK=creatine kinase; CPTII=carnitine palmitoyltransferase II; FAO=fatty acid oxidation; FFA=free fatty acids; LPIN1=lipin-1; Vo2max=maximal oxygen uptake