Defective fatty acid uptake modulates insulin responsiveness and metabolic responses to diet in CD36-null mice.
Deficiency of the membrane protein FAT/CD36 causes a marked defect in fatty acid uptake by various tissues and is genetically linked to insulin resistance in rats and humans. Here, we examined insulin responsiveness of CD36-/- mice. When fed a diet high in complex carbohydrates and low (5%) in fat, these animals cleared glucose faster than the wild-type. In vivo, uptake of 2-fluorodeoxyglucose by muscle was increased severalfold, and in vitro, insulin responsiveness of glycogenesis by the soleus was enhanced. Null mice had lower glycogen levels in muscle and liver, lower muscle triglyceride levels, and increased liver triglyceride content--all findings consistent with increased insulin-sensitivity. However, when the chow diet was switched to one high in fructose, CD36-/- mice but not wild-type mice developed marked glucose intolerance, hyperinsulinemia, and decreased muscle glucose uptake. High-fat diets impaired glucose tolerance equally in both groups, although CD36 deficiency helped moderate insulin-responsive muscle glucose oxidation. In conclusion, CD36 deficiency enhances insulin responsiveness on a high-starch, low-fat diet. It predisposes to insulin resistance induced by high fructose and partially protects from that induced by high-fat diets. In humans, CD36 deficiency may be an important factor in the metabolic adaptation to diet and in susceptibility to some forms of diet-induced pathology.
Hajri
Tahar
T
Department of Physiology and Biophysics, State University of New York at Stony Brook, New York 11794-8661, USA.
Han
Xiao Xia
XX
Bonen
Arend
A
Abumrad
Nada A
NA
D000818:Animals; D018955:CD36 Antigens; D004032:Diet; D005227:Fatty Acids / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D027361:Organic Anion Transporters / Q000235:genetics / Q000502:physiology*; D051381:Rats
D018955:CD36 Antigens; D005227:Fatty Acids; D008562:Membrane Glycoproteins; D027361:Organic Anion Transporters; D005947:Glucose