CD36-dependent fatty acid uptake regulates expression of peroxisome proliferator activated receptors.
CD36 is an important regulator of lipid metabolism in vivo due to its role in the facilitated uptake of long-chain FAs (fatty acids). CD36-deficient mice display reduced TAG (triacylglycerol) in muscle, but elevated hepatic TAG. Also, insulin sensitivity is enhanced peripherally, while it appears impaired in the liver. Tissues such as muscle, which normally express high levels of CD36, shift to high glucose utilization in CD36 deficiency, so we hypothesized that this shift must involve adaptive changes in the PPAR (peroxisome-proliferator-activated receptor) transcription factors which regulate FA metabolism. To test this, we examined mRNA levels for the three PPAR isoforms in tissues of WT (wild-type) and CD36-deficient mice following the administration of saline, glucose or olive oil by intragastric gavage. Compared with WT mice, CD36-null mice had 5-10-fold increased PPAR mRNA in adipose tissue in the basal state, and did not exhibit diet-induced changes. Correlations between adipose PPAR mRNA abundance and plasma lipids were observed in WT mice, but not in CD36-null mice. The opposite was true for hepatic PPAR mRNA levels, which correlated with plasma FA, TAG and/or glucose only in CD36-null mice. No significant differences were observed in PPAR mRNA levels in the intestine, where CD36 does not impact on FA uptake. The data suggest that CD36 and the PPARs are components of the FA-sensing machinery to respond to changes in FA flux in a tissue-specific manner.
Drover
V A
VA
Department of Physiology and Biophysics, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
Abumrad
N A
NA
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D018955:CD36 Antigens / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D017931:DNA Primers; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*
D018955:CD36 Antigens; D017931:DNA Primers; D005227:Fatty Acids; D047492:Peroxisome Proliferator-Activated Receptors