Fat metabolism disorders may stem from an abnormal fatty acid oxidation, which limits energy production during periods of increased energy requirement, such as muscular exertion; gastrointestinal disease; exposure to cold and fasting. Thus, obesity leads to diabetes, cardio-vascular illness, hypertension, metabolic syndrome, polycystic ovary syndrome, Syndrome X and sleep apnea. During energy utilization, fatty acids are broken down through beta-oxidation to yield acetyl-CoA. We have discovered the exciting link of a member of Kruppel-like factors (KLF) in lipid utilization by analyzing
klf-3 mutants of Caenorhabditis elegans and found that many metabolic genes are potential targets under the control of
klf-3 in triglycerides (TG) derived FA beta-oxidation. Three lines of data suggest the role of KLF-3 in FA beta-oxidation (1), KLF-3 protein is primarily expressed in the intestine; (2), Large lipid droplets storing TG are seen in
klf-3 mutant, 3): KLF-3 binds to the promoters of
fat-7 (Stearoyl-CoA desaturases, SCD),
acs-1,
acs-2(Acyl CoA synthase), and F08A8.1 (Acyl CoA oxidase) a set of genes essential for FA biosynthesis and beta-oxidation in C. elegans. The
klf-3 gene shows strong interaction with
acs-1,
acs-2, F08A8.1 and F08A8.2. Mutation in
klf-3 (
ok1975) causes impaired reproduction, suggesting that excessive fat deposition and reproductive defects may be intimately linked. To reconcile with these seemingly unrelated phenotypes of lipid utilization and reproductive behavior, we are examining
klf-3 gene function at biochemical, and developmental level, including genetic mosaic analysis of
klf-3 function in C. elegans. These results may elucidate the role of KLF transcription factors in fatty acid oxidation and reproduction.