Defective fatty acid uptake modulates insulin responsiveness and metabolic responses to diet in CD36-null mice
Tahar Hajri, … , Arend Bonen, Nada A. Abumrad
Tahar Hajri, … , Arend Bonen, Nada A. Abumrad
Published May 15, 2002
Citation Information: J Clin Invest. 2002;109(10):1381-1389. https://doi.org/10.1172/JCI14596.
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Article Genetics

Defective fatty acid uptake modulates insulin responsiveness and metabolic responses to diet in CD36-null mice

Abstract

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.

Authors

Tahar Hajri, Xiao Xia Han, Arend Bonen, Nada A. Abumrad

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Figure 1

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Response of blood glucose (a) and insulin (b) to a glucose load in CD36-...
Response of blood glucose (a) and insulin (b) to a glucose load in CD36-null (CD36–/–) and WT mice fed a standard chow diet. Twelve-week-old mice fasted for 16 hours were given glucose (1.5 mg/g) intraperitoneally. (a) Blood glucose was measured before and at 10, 20, 30, 45, 60, 120, and 180 minutes after glucose administration. Two-way repeated-measures ANOVA indicated a significant effect of the genotype (P < 0.05). The change of glucose response over time in each genotype (P < 0.05) and the interaction genotype × glucose are also significant (P < 0.05). *Significant differences (t test) between CD36–/– and WT at each time point. P < 0.01 for 20–60 minutes and P < 0.05 for 120 minutes. Inset shows areas under the glucose tolerance curves (AUC) (P < 0.01). (b) Plasma insulin levels were determined before the glucose injection and at 30 and 60 minutes after injection. *Insulin levels at 0 minutes are significantly lower in CD36–/– than in WT (P < 0.05). All data are means ± SEM with n = 12 (6 males and 6 females).