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 Kruppel-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 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. RESULTS: Klf-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 Ca(2+,) the expression of both
klf-2 and -3 was inhibited slightly; further their expression reduced significantly in WT worms fed on 10X Ca(2+) diet. When
klf-3 was mutated, the expression of
klf-2 increased under 10X Ca(2+) diet; but when
klf-2 was mutated, the expression of
klf-3 was not altered under 10X Ca(2+) diet. Overall, Mg(2+) 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 Ca(2+) concentrations but not in
klf-2 (
ok1043) worms. However, high Ca(+2) diet exhibited inhibitory effect on Ce-SREBP expression in WT worms. CONCLUSION: Dietary Ca(2+) is most effective on fat storage and
klf-2 expression, wherein high Ca(2+) 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.