Defective lipid metabolism associated with mutation in and : important roles of essential dietary salts in fat storage.

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 used mutants [homozygous (ok1043) V and (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 :: (in pPD95.75 vector) using a fluorescent microscope. Fat storage was measured by Oil Red O staining.

Results: was identified to express in the intestine during all stages of development with peak expression at L3 stage. Mutation of increased fat accumulation. Under regular growth media free of Ca the expression of both and - was inhibited slightly; further their expression reduced significantly in WT worms fed on 10X Ca diet. When was mutated, the expression of increased under 10X Ca diet; but when was mutated, the expression of was not altered under 10X Ca diet. Overall, Mg and K were less effective on the gene expression of . KLF target gene -C/EBP-2 showed elevated expression in WT and (ok1975) worms with changed Ca concentrations but not in (ok1043) worms. However, high Ca diet exhibited inhibitory effect on -SREBP expression in WT worms.

Conclusion: Dietary Ca is most effective on fat storage and expression, wherein high Ca diet decreased expression and reduced fat buildup. Mechanistic study identified -C/EBP (C48E7.3; ) and Ce-SREBP (Y47D3B.7; ) as the target genes of and/or to mediate lipid metabolism. This study identifies a new function of in inhibiting fat buildup and reveals the interplay between dietary salts and and in lipid metabolism.