27-OR: Fatty Acid Uptake and Metabolism in Human Adipose Tissue Is Decreased upon Consuming an Isocaloric High–Saturated Fat Diet and Partially Genetically Determined

Abstract

CD36 transports fatty acids (FA) into adipocytes and is increased in white adipose tissue (WAT) in obesity. In rodents, however, it was shown that CD36 knock out is protective for diet induced adiposity. In humans a hypocaloric high fat diet decreased CD36 gene expression in WAT. This study investigated the response of gene expression of FA uptake and metabolism in sub cutaneous WAT after a sudden switch from a healthy isocaloric low fat diet to an isocaloric high fat diet (HF) in healthy human twins. 35 monzyogotic and dizygotic healthy pairs of twins (women and men, age 18 - 70) were investigated for 12 weeks. An isocaloric diet rich in carbohydrates (55% carbohydrates, 30% fat, 15% protein, LF) was applied for 6 weeks, followed by an isocaloric diet rich in saturated fat (40% carbohydrates, 45% fat, 15% protein, HF) for another 6 weeks. Body weight (BW) , BMI, serum FA and gene expression of CD36, PDK4, PGC1α and CPT1α by qPCR were analyzed after the LF period, after one week (HF1) and at the end (HF6) of the HF period. BW did not change during the study. Serum FA were unchanged at HF1 but decreased at HF6 by 18% (P<0.compared to LF) . Gene expression of CD 36 was strongly decreased by 33% at HF1 and by 26% at HF6, respectively, compared to LF (both P<0.001) . A significant decrease of gene expression of PDK4 by 18% was observed at HF1 and by 27% at HF6 (both P<0.0compared to LF) . Gene expression of PGC1α and CPT1α were not changed at HF1 but decreased both at HF6 by 14% (both P<0.0compared to LF) and were highly heritable: 64% for PGC1α and 48% for CPT1α. Gene expression was positively correlated with BMI for CD36 at HF1 and for PDK4 at LF, HF1 and HF6 (P<0.05) . These data indicate that gene expression of transport (CD36) and re-esterification (PDK4) of FA are not only dependant on the amount of nutritional fat, but also on energy content. Moreover, expression of genes controlling mitochondrial (PGC1α) and FA (CPT1α) metabolism appear to be genetically determined. Disclosure M.Kruse: None. A.Ost: None. S.Hornemann: None. D.Hoffmann: None. T.Frahnow: None. A.Busjahn: None. A.F.Pfeiffer: None. Funding German Federal Ministry of Education and Research (0315424)