0000000000073739
AUTHOR
Isabelle Zaghini
Regulation of Farnesyl Diphosphate Synthase Gene Expression by Fatty Acids
Cholesterol biosynthesis depends on the activity of regulatory enzymes, including the peroxisomal Farnesyl Diphosphate Synthase (FPPS ). Cholesterol regulates its own synthesis rate. Hence, as a response to cholesterol depletion, a feed back mechanism is activated, whereby sterol regulatory binding proteins (SREBPla, 1c and 2 ) are subjected to sequential proteolytic activation, which permits their interaction with specific DNA response elements from responsive genes. In turn, the transcriptional activity of cholesterol biosynthesis genes is induced. Conversely, cholesterol accumulation decreases SREBP maturation and transcription of controlled genes. In addition, polyunsaturated fatty acid…
Effects of peroxisome proliferator-activated receptor alpha activation on pathways contributing to cholesterol homeostasis in rat hepatocytes
International audience; Peroxisome proliferator-activated receptor alpha (PPARa) activation by fibrates controls expression of several genes involved in hepatic cholesterol metabolism. Other genes could be indirectly controlled in response to changes in cellular cholesterol availability. To further understand how fibrates may affect cholesterol synthesis, we investigated in parallel the changes in the metabolic pathways contributing to cholesterol homeostasis in liver. Ciprofibrate increased HMG-CoA reductase and FPP synthase mRNA levels in rat hepatocytes, together with cholesterogenesis from [14C] acetate and [3H] mevalonate. The up-regulation observed in fenofibrate- and WY-14,643-treate…
Sterol Regulatory Element-binding Protein-1c Is Responsible for Cholesterol Regulation of Ileal Bile Acid-binding Protein Gene in Vivo
Ileal bile acid-binding protein (I-BABP) is a cytosolic protein that binds bile acid (BA) specifically. In the ileum, it is thought to be implied in their enterohepatic circulation. Because the fecal excretion of BA represents the main physiological way of elimination for cholesterol (CS), the I-BABP gene could have a major function in CS homeostasis. Therefore, the I-BABP gene expression might be controlled by CS. I-BABP mRNA levels were significatively increased when the human enterocyte-like CaCo-2 cells were CS-deprived and repressed when CS were added to the medium. A highly conserved sterol regularory element-like sequence (SRE) and a putative GC box were found in human I-BABP gene pr…
Hepatic farnesyl diphosphate synthase expression is suppressed by polyunsaturated fatty acids
Dietary vegetable oils and fish oils rich in PUFA (polyunsaturated fatty acids) exert hypocholesterolaemic and hypotriglyceridaemic effects in rodents. The plasma cholesterol-lowering properties of PUFA are due partly to a diminution of cholesterol synthesis and of the activity of the rate-limiting enzyme HMG-CoA reductase (3-hydroxy-3-methylglutaryl-CoA reductase). To better understand the mechanisms involved, we examined how tuna fish oil and individual n−3 and n−6 PUFA affect the expression of hepatic FPP synthase (farnesyl diphosphate synthase), a SREBP (sterol regulatory element-binding protein) target enzyme that is subject to negative-feedback regulation by sterols, in co-ordination …