PMID- 21704635
OWN - NLM
STAT- MEDLINE
DCOM- 20111003
LR  - 20211020
IS  - 1089-8638 (Electronic)
IS  - 0022-2836 (Print)
IS  - 0022-2836 (Linking)
VI  - 411
IP  - 3
DP  - 2011 Aug 19
TI  - Regulation of fat storage and reproduction by Kruppel-like transcription factor 
      KLF3 and fat-associated genes in Caenorhabditis elegans.
PG  - 537-53
LID - 10.1016/j.jmb.2011.06.011 [doi]
AB  - 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, Kruppel-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) beta-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 beta-oxidation and, in parallel, may contribute to normal 
      reproductive behavior and fecundity in C. elegans.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Zhang, Jun
AU  - Zhang J
AD  - Laboratory of Developmental Biology, Lindsley F. Kimball Research Institute, New 
      York Blood Center, 310 East 67th Street, New York, NY 10065, USA.
FAU - Bakheet, Razan
AU  - Bakheet R
FAU - Parhar, Ranjit S
AU  - Parhar RS
FAU - Huang, Cheng-Han
AU  - Huang CH
FAU - Hussain, M Mahmood
AU  - Hussain MM
FAU - Pan, Xiaoyue
AU  - Pan X
FAU - Siddiqui, Shahid S
AU  - Siddiqui SS
FAU - Hashmi, Sarwar
AU  - Hashmi S
LA  - eng
GR  - R01 DK046900/DK/NIDDK NIH HHS/United States
GR  - R01 DK081879/DK/NIDDK NIH HHS/United States
GR  - R01 HL095924/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20110617
PL  - Netherlands
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (Fatty Acids)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Triglycerides)
RN  - EC 1.14.19.1 (Stearoyl-CoA Desaturase)
RN  - EC 1.3.3.6 (Acyl-CoA Oxidase)
RN  - EC 6.2.1.- (Coenzyme A Ligases)
RN  - EC 6.2.1.13 (acetate-CoA ligase (ADP-forming))
SB  - IM
MH  - Acyl-CoA Oxidase/metabolism
MH  - Adipose Tissue/physiology
MH  - Animals
MH  - Caenorhabditis elegans/genetics/metabolism/*physiology
MH  - Coenzyme A Ligases/metabolism
MH  - Cytosol/metabolism
MH  - *Energy Metabolism
MH  - Fatty Acids/biosynthesis
MH  - Fertility
MH  - Intestinal Mucosa/metabolism
MH  - Kruppel-Like Transcription Factors/*genetics/*metabolism
MH  - Larva/growth & development
MH  - *Lipid Metabolism
MH  - Mitochondria/metabolism
MH  - Mutation
MH  - Oxidation-Reduction
MH  - Peroxisomes/metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering
MH  - Reproduction
MH  - Stearoyl-CoA Desaturase/metabolism
MH  - Triglycerides/metabolism
PMC - PMC4371853
MID - NIHMS672319
EDAT- 2011/06/28 06:00
MHDA- 2011/10/04 06:00
PMCR- 2015/03/24
CRDT- 2011/06/28 06:00
PHST- 2011/03/17 00:00 [received]
PHST- 2011/06/06 00:00 [revised]
PHST- 2011/06/07 00:00 [accepted]
PHST- 2011/06/28 06:00 [entrez]
PHST- 2011/06/28 06:00 [pubmed]
PHST- 2011/10/04 06:00 [medline]
PHST- 2015/03/24 00:00 [pmc-release]
AID - S0022-2836(11)00648-6 [pii]
AID - 10.1016/j.jmb.2011.06.011 [doi]
PST - ppublish
SO  - J Mol Biol. 2011 Aug 19;411(3):537-53. doi: 10.1016/j.jmb.2011.06.011. Epub 2011 
      Jun 17.