Free fatty acid uptake in humans with CD36 deficiency

Animal models have demonstrated that CD36 facilitates cell membrane free fatty acid (FFA) transport, but its role in human metabolism is not well understood. We measured heart, liver, adipose (three depots), and muscle (truncal postural and thigh locomotive) FFA uptake using [11C]palmitate positron emission tomography (PET) scans in a family of five carrying the Pro90Ser CD36 mutation (2 homozygotes had no CD36) and matched control volunteers. PET scans were done under conditions of suppressed and slightly increased palmitate concentrations. During suppressed palmitate conditions, muscle and adipose palmitate uptake were markedly reduced in homozygotes but not heterozygotes for the Pro90Ser CD36 mutation, whereas when palmitate concentration was slightly increased, uptake in muscle and adipose did not differ between control subjects and homozygous family members. Hepatic FFA uptake was similar in all participants regardless of palmitate concentrations, whereas myocardial FFA uptake was diminished in the Pro90Ser homozygotes during both suppressed and increased palmitate conditions. We conclude that CD36 1) facilitates FFA transport into muscle and adipose tissue in humans when extracellular concentrations are reduced but not when they are modestly elevated, 2) is not rate limiting for hepatic FFA uptake, and 3) is needed for normal cardiac FFA uptake over a range of FFA concentrations from low to slightly elevated.