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The lin-4 gene controls fat accumulation and longevity in Caenorhabditis elegans.

Zhu C, Ji CB, Zhang CM, Gao CL, Zhu JG, Qin DN, Kou CZ, Zhu GZ, Shi CM, Guo XR - Int J Mol Sci (2010)

Bottom Line: In this study, we showed that the fat content is reduced remarkably in C. elegans lin-4 mutants.We also showed that lin-4 mutants have a significantly shorter life span than wild-type worms.DCF assay experiments showed that the reactive oxygen species (ROS) levels increased and mitochondrial DNA (mtDNA) copy number decreased in loss-of-function lin-4 mutants.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Nanjing Maternal and Child Health Hospital of Nanjing Medical University, No.123 Tianfei Road, 210004 Nanjing, China; E-Mails: zhifangxibao@163.com (C.Z.); zhangcm79@163.com (C.-M.Z.).

ABSTRACT
Previous studies have determined that lin-4, which was the first miRNA to be discovered, controls the timing of cell fate determination and life span in Caenorhabditis elegans. However, the mechanism of lin-4 involvement in these processes remains poorly understood. Fat storage is an essential aspect of the life cycle of organisms, and the function of lin-4 in fat accumulation is not clear. In this study, we showed that the fat content is reduced remarkably in C. elegans lin-4 mutants. Quantitative RT-PCR analysis revealed a considerable decrease in the levels of SBP-1 and OGA-1 mRNA in lin-4 mutants. We also showed that lin-4 mutants have a significantly shorter life span than wild-type worms. DCF assay experiments showed that the reactive oxygen species (ROS) levels increased and mitochondrial DNA (mtDNA) copy number decreased in loss-of-function lin-4 mutants. These mutants also showed attenuation of locomotion. Taken together, our findings suggest that lin-4 may play an important role in regulating fat accumulation and locomotion and that lin-4 may control the life span of C. elegans by mediating ROS production.

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The expression of central regulation factors involved in fat storage control in nematodes. (A) Quantitative real-time PCR of sbp-1 in wild-type (N2) and lin-4 mutant (e912) worms. n = 50 (n: number); (B) Quantitative real-time PCR of oga-1 in wild-type (N2) and lin-4 mutant (e912) worms. n = 40. Error bars indicate standard error. * p < 0.05.
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f2-ijms-11-04814: The expression of central regulation factors involved in fat storage control in nematodes. (A) Quantitative real-time PCR of sbp-1 in wild-type (N2) and lin-4 mutant (e912) worms. n = 50 (n: number); (B) Quantitative real-time PCR of oga-1 in wild-type (N2) and lin-4 mutant (e912) worms. n = 40. Error bars indicate standard error. * p < 0.05.

Mentions: As shown in Figure 1, when worms were fed a normal diet of E. coli OP50 bacteria, animals with a loss-of-function mutation in lin-4 showed fat content that was significantly lower than that in wild-type animals. After adding glucose and fatty acid to culture dishes containing C. elegans, we found an increase in fluorescence in Nile red staining, thereby indicating an increase in intracellular fat. However, fat levels were also reduced considerably in lin-4 mutants compared to wild-type animals. To determine whether the key genes in the metabolic pathways for fatty acid synthesis in nematodes are involved in regulating fat accumulation, we measured mRNA levels of SBP-1 and OGA-1 by using quantitative RT-PCR analysis. We found that both SBP-1 and OGA-1 mRNA levels were reduced in lin-4 mutants, especially SBP-1(Figure 2).


The lin-4 gene controls fat accumulation and longevity in Caenorhabditis elegans.

Zhu C, Ji CB, Zhang CM, Gao CL, Zhu JG, Qin DN, Kou CZ, Zhu GZ, Shi CM, Guo XR - Int J Mol Sci (2010)

The expression of central regulation factors involved in fat storage control in nematodes. (A) Quantitative real-time PCR of sbp-1 in wild-type (N2) and lin-4 mutant (e912) worms. n = 50 (n: number); (B) Quantitative real-time PCR of oga-1 in wild-type (N2) and lin-4 mutant (e912) worms. n = 40. Error bars indicate standard error. * p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3100830&req=5

f2-ijms-11-04814: The expression of central regulation factors involved in fat storage control in nematodes. (A) Quantitative real-time PCR of sbp-1 in wild-type (N2) and lin-4 mutant (e912) worms. n = 50 (n: number); (B) Quantitative real-time PCR of oga-1 in wild-type (N2) and lin-4 mutant (e912) worms. n = 40. Error bars indicate standard error. * p < 0.05.
Mentions: As shown in Figure 1, when worms were fed a normal diet of E. coli OP50 bacteria, animals with a loss-of-function mutation in lin-4 showed fat content that was significantly lower than that in wild-type animals. After adding glucose and fatty acid to culture dishes containing C. elegans, we found an increase in fluorescence in Nile red staining, thereby indicating an increase in intracellular fat. However, fat levels were also reduced considerably in lin-4 mutants compared to wild-type animals. To determine whether the key genes in the metabolic pathways for fatty acid synthesis in nematodes are involved in regulating fat accumulation, we measured mRNA levels of SBP-1 and OGA-1 by using quantitative RT-PCR analysis. We found that both SBP-1 and OGA-1 mRNA levels were reduced in lin-4 mutants, especially SBP-1(Figure 2).

Bottom Line: In this study, we showed that the fat content is reduced remarkably in C. elegans lin-4 mutants.We also showed that lin-4 mutants have a significantly shorter life span than wild-type worms.DCF assay experiments showed that the reactive oxygen species (ROS) levels increased and mitochondrial DNA (mtDNA) copy number decreased in loss-of-function lin-4 mutants.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Nanjing Maternal and Child Health Hospital of Nanjing Medical University, No.123 Tianfei Road, 210004 Nanjing, China; E-Mails: zhifangxibao@163.com (C.Z.); zhangcm79@163.com (C.-M.Z.).

ABSTRACT
Previous studies have determined that lin-4, which was the first miRNA to be discovered, controls the timing of cell fate determination and life span in Caenorhabditis elegans. However, the mechanism of lin-4 involvement in these processes remains poorly understood. Fat storage is an essential aspect of the life cycle of organisms, and the function of lin-4 in fat accumulation is not clear. In this study, we showed that the fat content is reduced remarkably in C. elegans lin-4 mutants. Quantitative RT-PCR analysis revealed a considerable decrease in the levels of SBP-1 and OGA-1 mRNA in lin-4 mutants. We also showed that lin-4 mutants have a significantly shorter life span than wild-type worms. DCF assay experiments showed that the reactive oxygen species (ROS) levels increased and mitochondrial DNA (mtDNA) copy number decreased in loss-of-function lin-4 mutants. These mutants also showed attenuation of locomotion. Taken together, our findings suggest that lin-4 may play an important role in regulating fat accumulation and locomotion and that lin-4 may control the life span of C. elegans by mediating ROS production.

Show MeSH