Mutation in Caenorhabditis elegans Krüppel-like factor, KLF-3 results in fat accumulation and alters fatty acid composition

Zhang, Jun; Yang, Chuan; Brey, Christopher W.; Rodriguez, Marilis; Oksov, Yelena; Gaugler, Randy; Dickstein, E. R.; Huang, Cheng Han; Hashmi, Sarwar

doi:10.1016/j.yexcr.2009.04.025

Cited by 29 publications

(46 citation statements)

References 45 publications

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“…15 Their protein products differ by 8 amino acids in their N-terminus but share the 301 C-terminal amino acids encoded by common exons†. A previous study of klf-3 has described its expression and mutant phenotypes.…”

Section: Resultsmentioning

confidence: 99%

“…Reporter gene studies showed that a 1-kb segment 5′ terminal to the klf-3a ATG start codon directs a very strong intestinal expression. 15 To determine the in vivo tissue expression of klf-3b , we established transgenic lines carrying the klf-3b ∷ gfp fusion gene, which was driven by the cognate promoter, a 2.0-kb genomic sequence upstream of the first ATG codon (pHZ145; Fig. 1a).…”

Section: Resultsmentioning

confidence: 99%

“…In our previous studies, we found that a decrease in the mRNA levels of SCD fat-7 in klf-3 mutant animals was associated with changes in the composition and ratio of FAs. 15 Analysis of the fat-7 ( wa36 ) mutant revealed a single base-pair change that causes premature termination of the transcript and thus defines a loss-of-function allele. 27 The fat-7 gene is expressed in the intestine, and the fat-7 ( wa36 ) mutant displays a normal life span with no obvious defect in reproduction.…”

Section: Resultsmentioning

confidence: 99%

“…We showed previously that the expression of several genes key to FA metabolism ( acs-1 , acs-2 , F08A8.1 , and F08A8.2 , involving mitochondrial/peroxisomal β-oxidation, and fat-7 , a desaturase gene) was significantly altered in klf-3 ( ok1975 ) mutants. 15 Thus, we hypothesize that the excessive fat deposits and severe fertility defects observed in klf-3 mutants result from accumulative perturbation of FA metabolism, which causes gradual damage to reproduction in the course of worm development.…”

Section: Introductionmentioning

confidence: 98%

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Regulation of Fat Storage and Reproduction by Krüppel-Like Transcription Factor KLF3 and Fat-Associated Genes in Caenorhabditis elegans

Zhang

Bakheet

Parhar

et al. 2011

Journal of Molecular Biology

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Coordinated regulation of fat storage and utilization is essential for energy homeostasis, and its disruption is associated with metabolic syndrome and atherosclerosis in humans. Across species, Krüppel-like transcription factors (KLFs) have been identified as key components of adipogenesis. In humans, KLF14 acts as a master transregulator of adipose gene expression in type 2 diabetes and cis-acting expression quantitative trait locus associated with high-density lipoprotein cholesterol. Herein we report that, in Caenorhabditis elegans, mutants in klf-3 accumulate large fat droplets rich in neutral lipids in the intestine; this lipid accumulation is associated with an increase in triglyceride levels. The klf-3 mutants show normal pharyngeal pumping; however, they are sterile or semisterile. We explored important genetic interactions of klf-3 with the genes encoding enzymes involved in fatty acid (FA) β-oxidation in mitochondria or peroxisomes and FA synthesis in the cytosol, namely acyl-CoA synthetase (acs-1 and acs-2), acyl-CoA oxidase (F08A8.1 and F08A8.2), and stearoyl-CoA desaturase (fat-7). We show that mutations or RNA interference in these genes increases fat deposits in the intestine of acs-1, acs-2, F08A8.1, and F08A8 animals. We further show that acs-1 and F08A8.1 influence larval development and fertility, respectively. Thus, KLF3 may regulate FA utilization in the intestine and reproductive tissue. We demonstrate that depletion of F08A8.1 activity, but not of acs-1, acs-2, F08A8.2, or fat-7 activity, enhances the fat phenotype of the klf-3 mutant. Taken together, these results suggest that klf-3 regulates lipid metabolism, along with acs-1, acs-2, F08A8.1, and F08A8.2, by promoting FA β-oxidation and,in parallel, may contribute to normal reproductive behavior and fecundity in C.elegans.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Regulation of Fat Storage and Reproduction by Krüppel-Like Transcription Factor KLF3 and Fat-Associated Genes in Caenorhabditis elegans

Zhang

Bakheet

Parhar

et al. 2011

Journal of Molecular Biology

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“…21) Herein, the suppression of FASN promoter activity by KLF3 indicated that, besides the role of maintaining normal fatty acid composition by regulating genes involved in a fatty acid desaturation pathway revealed in C. elegans, 22) KLF3 might also inhibit de novo fatty acid synthesis in chicken.…”

Section: Discussionmentioning

confidence: 99%

Expression and functional analyses of Krüppel-like factor 3 in chicken adipose tissue

Zhang

et al. 2014

Bioscience, Biotechnology, and Biochemistry

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Studies in mammalian species showed that Krüppel-like factor 3 (KLF3) regulated adipose tissue development. However, it was not reported in chicken. In the current study, we found that during the growth and development of abdominal fat tissue, chicken KLF3 (Gallus gallus KLF3, gKLF3) was consecutively expressed, and its transcripts were higher at 7 weeks of age and lower at 10 weeks of age in lean broilers than in fat broilers. In addition, gKLF3 overexpression suppressed chicken CCAAT/enhancer binding protein alpha (C/EBPα), fatty acid binding protein 4 (FABP4), fatty acid synthase (FASN), and lipoprotein lipase (LPL) promoter activities, but increased chicken peroxisome proliferator-activated receptor gamma (PPARγ) promoter activity. Additionally, point mutagenesis analysis showed that the substitution of Asp by Gly within the Pro-Val-Asp-Leu-Thr (PVDLT) motif of gKLF3 significantly reduced the ability of gKLF3 to regulate the promoter activities of FABP4, FASN, LPL, C/EBPα, and PPARγ.

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Polymorphisms of KLF3 gene coding region and identification of their functionality for abdominal fat in chickens

Wang

et al. 2020

Veterinary Medicine & Sci

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Mutation in Caenorhabditis elegans Krüppel-like factor, KLF-3 results in fat accumulation and alters fatty acid composition

Cited by 29 publications

References 45 publications

Regulation of Fat Storage and Reproduction by Krüppel-Like Transcription Factor KLF3 and Fat-Associated Genes in Caenorhabditis elegans

Regulation of Fat Storage and Reproduction by Krüppel-Like Transcription Factor KLF3 and Fat-Associated Genes in Caenorhabditis elegans

Expression and functional analyses of Krüppel-like factor 3 in chicken adipose tissue

Polymorphisms of KLF3 gene coding region and identification of their functionality for abdominal fat in chickens

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