title: Defective lipid metabolism associated with mutation inklf-2andklf-3: important roles of essential dietary salts in fat storage.
abstract: BACKGROUND
  Dietary salts are important factors in metabolic disorders. They are vital components of enzymes, vitamins, hormones, and signal transduction that act synergistically to regulate lipid metabolism. Our previous studies have identified that Krüppel-like factor -3 (KLF-3) is an essential regulator of lipid metabolism. However, it is not known if KLF-2 also regulates lipid metabolism and whether KLF-2 and -3 mediate the effects of dietary salts on lipid metabolism.
  
  
  METHODS
  In this study, we usedklfmutants [homozygousklf-2(ok1043) V andklf-3(ok1975) II mutants] to investigate the role of dietary salts in lipid metabolism. All gene expression was quantified by qRT-PCR. Localization of KLF-2 was analyzed by the expression ofklf-2::gfp(in pPD95.75 vector) using a fluorescent microscope. Fat storage was measured by Oil Red O staining.
  
  
  RESULTS
  Klf-2was identified to express in the intestine during all stages ofCaenorhabditis elegansdevelopment with peak expression at L3 stage. Mutation ofklf-2increased fat accumulation. Under regular growth media free of Ca2+,the expression of bothklf-2and -3was inhibited slightly; further their expression reduced significantly in WT worms fed on 10X Ca2+diet. Whenklf-3was mutated, the expression ofklf-2increased under 10X Ca2+diet; but whenklf-2was mutated, the expression ofklf-3was not altered under 10X Ca2+diet. Overall, Mg2+and K+were less effective on the gene expression ofklfs. KLF target geneCe-C/EBP-2 showed elevated expression in WT andklf-3(ok1975) worms with changed Ca2+concentrations but not inklf-2(ok1043) worms. However, high Ca+2diet exhibited inhibitory effect onCe-SREBP expression in WT worms.
  
  
  CONCLUSIONS
  Dietary Ca2+is most effective on fat storage andklf-2expression, wherein high Ca2+diet decreasedklf-2expression and reduced fat buildup. Mechanistic study identifiedCe-C/EBP (C48E7.3;lpd-2) and Ce-SREBP (Y47D3B.7;lpd-1) as the target genes ofklf-2and/orklf-3to mediate lipid metabolism. This study identifies a new function ofklf-2in inhibiting fat buildup and reveals the interplay between dietary salts andklf-2andklf-3in lipid metabolism.
authors.affiliation: Department of Basic Sciences, Geisinger Commonwealth School of Medicine, 525 Pine Street, Scranton, PA 18509 USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Ling
authors.affiliation: Science Department, Marywood University, Scranton, PA 18509 USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Brey
authors.affiliation: Molecular, Cellular and Integrative Biosciences Huck Institute of the Life Sciences, The Pennsylvania State University, University Park, PA 16802 USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Schilling
authors.affiliation: Laboratory of Developmental Biology, Center for Vector Biology, Rutgers University, 180, Jones Avenue, New Brunswick, NJ 08901 USA.
authors.forename: Farah
authors.initials: F
authors.lastname: Lateef
authors.affiliation: Department of Basic Sciences, Geisinger Commonwealth School of Medicine, 525 Pine Street, Scranton, PA 18509 USA.
authors.forename: Zenaida P
authors.initials: ZP
authors.lastname: Lopez-Dee
authors.affiliation: Laboratory of Developmental Biology, Center for Vector Biology, Rutgers University, 180, Jones Avenue, New Brunswick, NJ 08901 USA.
authors.forename: Kristopher
authors.initials: K
authors.lastname: Fernandes
authors.affiliation: Laboratory of Developmental Biology, Center for Vector Biology, Rutgers University, 180, Jones Avenue, New Brunswick, NJ 08901 USA.
authors.forename: Kavita
authors.initials: K
authors.lastname: Thiruchelvam
authors.affiliation: Laboratory of Developmental Biology, Center for Vector Biology, Rutgers University, 180, Jones Avenue, New Brunswick, NJ 08901 USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Developmental Biology, Center for Vector Biology, Rutgers University, 180, Jones Avenue, New Brunswick, NJ 08901 USA.
authors.forename: Kshitij
authors.initials: K
authors.lastname: Chandel
authors.affiliation: Laboratory of Developmental Biology, Center for Vector Biology, Rutgers University, 180, Jones Avenue, New Brunswick, NJ 08901 USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Rau
authors.affiliation: Department of Cell Biology-Cardiovascular unit, KFSH&RC, Riyadh, Saudi Arabia.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Parhar
authors.affiliation: Department of Cell Biology-Cardiovascular unit, KFSH&RC, Riyadh, Saudi Arabia.
authors.forename: Futwan
authors.initials: F
authors.lastname: Al-Mohanna
authors.affiliation: Laboratory of Developmental Biology, Center for Vector Biology, Rutgers University, 180, Jones Avenue, New Brunswick, NJ 08901 USA.
authors.forename: Randy
authors.initials: R
authors.lastname: Gaugler
authors.affiliation: Laboratory of Developmental Biology, Center for Vector Biology, Rutgers University, 180, Jones Avenue, New Brunswick, NJ 08901 USA.|Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, & Health, Rutgers University, New Brunswick, NJ 08901 USA.
authors.forename: Sarwar
authors.initials: S
authors.lastname: Hashmi
keywords: Caenorhabditis elegans (C. elegans); Dietary salt; KLF mutant; KLF-2; KLF-3; Krüppel like factor (KLF); Lipid metabolism