title: Regulation of lipoprotein assembly, secretion and fatty acid β-oxidation by Krüppel-like transcription factor, klf-3.
abstract: Lipid metabolism is coordinately regulated through signaling networks that integrate biochemical pathways of fat assimilation, mobilization and utilization. Excessive diversion of fat for storage is a key risk factor for many fat-related human diseases. Dietary lipids are absorbed from the intestines and transported to various organs and tissues to provide energy and maintain lipid homeostasis. In humans, disparity between triglycerides (TG) synthesis and removal, via mitochondrial β-oxidation and VLDL (very low density lipoprotein) secretion, causes excessive TG accumulation in the liver. The mutation in Caenorhabditis elegans KLF-3 leads to high TG accumulation in the worm's intestine. Our previous data suggested that klf-3 regulates lipid metabolism by promoting fatty acid β-oxidation. Depletion of cholesterol in the diet has no effect on fat deposition in klf-3 (ok1975) mutants. Addition of vitamin D in the diet, however, increases fat levels in klf-3 worms. This suggests that excess vitamin D may be lowering the rate of fatty acid β-oxidation, with the eventual increase in fat accumulation. We also demonstrate that mutation in klf-3 reduces expression of C. elegans dsc-4 and/or vit genes, the orthologs of mammalian microsomal triglyceride transfer protein and apolipoprotein B, respectively. Both microsomal triglyceride transfer protein and apolipoprotein B are essential for mammalian lipoprotein assembly and transport, and mutation in both dsc-4 (qm182) and vit-5 (ok3239) results in high fat accumulation in worm intestine. Genetic interactions between klf-3 and dsc-4, as well as vit-5 genes, suggest that klf-3 may have an important role in regulating lipid assembly and secretion.
authors: Developmental Biology, New York Blood Center, New York, NY 10065, USA.
authors: Jun
authors: J
authors: Zhang
authors: Sanya
authors: S
authors: Hashmi
authors: Fatima
authors: F
authors: Cheema
authors: Nafla
authors: N
authors: Al-Nasser
authors: Razan
authors: R
authors: Bakheet
authors: Ranjit S
authors: RS
authors: Parhar
authors: Futwan
authors: F
authors: Al-Mohanna
authors: Randy
authors: R
authors: Gaugler
authors: M Mahmood
authors: MM
authors: Hussain
authors: Sarwar
authors: S
authors: Hashmi
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005786:Gene Expression Regulation; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D005227:Fatty Acids; C583288:KLF-3 protein, C elegans; D051741:Kruppel-Like Transcription Factors; D008074:Lipoproteins; D050505:Mutant Proteins; D014157:Transcription Factors
keywords: 4′,6-diamidino-2-phenylindole; C. elegans; DAPI; FA; IFA; MTP; NGM; PBS; PUFA; RT-PCR; apoB; apolipoprotein B; fatty acid; fatty acid β-oxidation; immunofluorescence assay; klf; lipoprotein assembly and secretion; microsomal triglyceride transfer protein; nematode growth medium; phosphate-buffered saline; polyunsaturated fatty acid; real-time PCR
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