title: Differential effect of fructose on fat metabolism and clock gene expression in hepatocytes vs. myotubes.
abstract: In the liver, fructose bypasses the main rate-limiting step of glycolysis at the level of phosphofructokinase, allowing it to act as an unregulated substrate for de novo lipogenesis. It has been reported that consumption of large amounts of fructose increases de novo lipogenesis in the liver. However, the effect of fructose on ectopic deposition of muscle fat has been under dispute. Our aim was to study the effect of fructose on levels of genes and proteins involved in fatty acid oxidation and synthesis in hepatocytes vs. muscle cells. In addition, as fat accumulation leads to disruption of daily rhythms, we tested the effect of fructose treatment on clock gene expression. AML-12 hepatocytes and C2C12 myotubes were treated with fructose or glucose for 2 consecutive 24-h cycles and harvested every 6h. In contrast to glucose, fructose disrupted clock gene rhythms in hepatocytes, but in myotubes, it led to more robust rhythms. Fructose led to low levels of phosphorylated AMP-activated protein kinase (pAMPK) and high levels of LIPIN1 in hepatocytes compared with glucose. In contrast, fructose led to high pAMPK and low LIPIN1 and microsomal triacylglycerol transfer protein (MTTP) levels in myotubes compared with glucose. Analysis of fat content revealed that fructose led to less fat accumulation in myotubes compared to hepatocytes. In summary, fructose shifts metabolism towards fatty acid synthesis and clock disruption in hepatocytes, but not in myotubes.
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
authors.forename: Nava
authors.initials: N
authors.lastname: Chapnik
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
authors.forename: Sigal
authors.initials: S
authors.lastname: Rozenblit-Susan
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
authors.forename: Yoni
authors.initials: Y
authors.lastname: Genzer
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel. Electronic address: oren.froy@mail.huji.ac.il.
authors.forename: Oren
authors.initials: O
authors.lastname: Froy
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D005632:Fructose; D005947:Glucose
keywords: C2C12; Clock; Fat; Fructose; Hepatocytes; Metabolism