Abstract
BackgroundDietary 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.MethodsIn this study, we used klf mutants [homozygous klf-2 (ok1043) V and klf-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 of klf-2::gfp (in pPD95.75 vector) using a fluorescent microscope. Fat storage was measured by Oil Red O staining.ResultsKlf-2 was identified to express in the intestine during all stages of Caenorhabditis elegans development with peak expression at L3 stage. Mutation of klf-2 increased fat accumulation. Under regular growth media free of Ca2+, the expression of both klf-2 and −3 was inhibited slightly; further their expression reduced significantly in WT worms fed on 10X Ca2+ diet. When klf-3 was mutated, the expression of klf-2 increased under 10X Ca2+ diet; but when klf-2 was mutated, the expression of klf-3 was not altered under 10X Ca2+ diet. Overall, Mg2+ and K+ were less effective on the gene expression of klfs. KLF target gene Ce-C/EBP-2 showed elevated expression in WT and klf-3 (ok1975) worms with changed Ca2+ concentrations but not in klf-2 (ok1043) worms. However, high Ca+2 diet exhibited inhibitory effect on Ce-SREBP expression in WT worms.ConclusionDietary Ca2+ is most effective on fat storage and klf-2 expression, wherein high Ca2+ diet decreased klf-2 expression and reduced fat buildup. Mechanistic study identified Ce-C/EBP (C48E7.3; lpd-2) and Ce-SREBP (Y47D3B.7; lpd-1) as the target genes of klf-2 and/or klf-3 to mediate lipid metabolism. This study identifies a new function of klf-2 in inhibiting fat buildup and reveals the interplay between dietary salts and klf-2 and klf-3 in lipid metabolism.
Highlights
Dietary salts are important factors in metabolic disorders
Klf-2 is differentially expressed during all developmental stages of the worm We examined the mRNA transcripts of klf-2 in embryos, larvae and adult stages of WT worm during development using qRT-PCR
We found that the expression of CEBP (Ce-lpd-2) was up-regulated in WT worms by various concentrations of Ca2+ but not in klf-2; it was slightly upregulated in klf-3 worms fed on the same diet (Fig. 5a), suggesting the up-regulation of CEBP (Ce-lpd2) expression in lipid formation may be more dependent on klf-2 than klf-3
Summary
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. Dietary salts function through enzymes, vitamins, hormones and signal transduction to collectively regulate lipid metabolism. The KLF proteins are key regulators of respiratory, hematological, and immune systems Their dysregulation can lead to many serious human diseases [12,13,14,15,16], which are supported by molecular mechanisms that KLFs can regulate for example cell differentiation, proliferation, signal transduction, adipogenesis, and apoptosis [17,18,19,20]
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