scholarly journals Dopamine Signaling Regulates Fat Content through β-Oxidation in Caenorhabditis elegans

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e85874 ◽  
Author(s):  
Alexandre Guimarães de Almeida Barros ◽  
Jessika Cristina Bridi ◽  
Bruno Rezende de Souza ◽  
Célio de Castro Júnior ◽  
Karen Cecília de Lima Torres ◽  
...  
IUBMB Life ◽  
2012 ◽  
Vol 64 (7) ◽  
pp. 644-648 ◽  
Author(s):  
Claudia Miersch ◽  
Frank Döring

2016 ◽  
Vol 113 (32) ◽  
pp. E4620-E4629 ◽  
Author(s):  
Daniel Z. Bar ◽  
Chayki Charar ◽  
Jehudith Dorfman ◽  
Tam Yadid ◽  
Lionel Tafforeau ◽  
...  

Dietary restriction (DR) is a metabolic intervention that extends the lifespan of multiple species, including yeast, flies, nematodes, rodents, and, arguably, rhesus monkeys and humans. Hallmarks of lifelong DR are reductions in body size, fecundity, and fat accumulation, as well as slower development. We have identified atx-2, the Caenorhabditis elegans homolog of the human ATXN2L and ATXN2 genes, as the regulator of these multiple DR phenotypes. Down-regulation of atx-2 increases the body size, cell size, and fat content of dietary-restricted animals and speeds animal development, whereas overexpression of atx-2 is sufficient to reduce the body size and brood size of wild-type animals. atx-2 regulates the mechanistic target of rapamycin (mTOR) pathway, downstream of AMP-activated protein kinase (AMPK) and upstream of ribosomal protein S6 kinase and mTOR complex 1 (TORC1), by its direct association with Rab GDP dissociation inhibitor β, which likely regulates RHEB shuttling between GDP-bound and GTP-bound forms. Taken together, this work identifies a previously unknown mechanism regulating multiple aspects of DR, as well as unknown regulators of the mTOR pathway. They also extend our understanding of diet-dependent growth retardation, and offers a potential mechanism to treat obesity.


2021 ◽  
Author(s):  
Chayki Charar ◽  
Sally Metsuyanim-Cohen ◽  
Daniel Z. Bar

Animals subjected to dietary restriction (DR) have reduced body size, low fecundity, slower development, lower fat content and longer life span. We identified lamin as a regulator of multiple dietary restriction phenotypes. Downregulation of lmn-1, the single Caenorhabditis elegans lamin gene, increased animal size and fat content, specifically in DR animals. The LMN-1 protein acts in the mTOR pathway, upstream to RAPTOR and S6K, key component and target of mTOR complex 1 (mTORC1), respectively. DR excludes the mTORC1 activator RAGC-1 from the nucleus. Downregulation of lmn-1 restores RAGC-1 to the nucleus, a necessary step for the activation of the mTOR pathway. These findings further link lamin to metabolic regulation.


2006 ◽  
Vol 26 (4-6) ◽  
pp. 591-616 ◽  
Author(s):  
Paul W. McDonald ◽  
Tammy Jessen ◽  
Julie R. Field ◽  
Randy D. Blakely

2004 ◽  
Vol 7 (10) ◽  
pp. 1096-1103 ◽  
Author(s):  
Daniel L Chase ◽  
Judy S Pepper ◽  
Michael R Koelle

2004 ◽  
Vol 379 (1) ◽  
pp. 191-198 ◽  
Author(s):  
You-Jun FEI ◽  
Jin-Cai LIU ◽  
Katsuhisa INOUE ◽  
Lina ZHUANG ◽  
Katsuya MIYAKE ◽  
...  

We have cloned and functionally characterized an Na+-coupled citrate transporter from Caenorhabditis elegans (ceNAC-2). This transporter shows significant sequence homology to Drosophila Indy and the mammalian Na+-coupled citrate transporter NaCT (now known as NaC2). When heterologously expressed in a mammalian cell line or in Xenopus oocytes, the cloned ceNAC-2 mediates the Na+-coupled transport of various intermediates of the citric acid cycle. However, it transports the tricarboxylate citrate more efficiently than dicarboxylates such as succinate, a feature different from that of ceNAC-1 (formerly known as ceNaDC1) and ceNAC-3 (formerly known as ceNaDC2). The transport process is electrogenic, as evidenced from the substrate-induced inward currents in oocytes expressing the transporter under voltage-clamp conditions. Expression studies using a reporter-gene fusion method in transgenic C. elegans show that the gene is expressed in the intestinal tract, the organ responsible for not only the digestion and absorption of nutrients but also for the storage of energy in this organism. Functional knockdown of the transporter by RNAi (RNA interference) not only leads to a significant increase in life span, but also causes a significant decrease in body size and fat content. The substrates of ceNAC-2 play a critical role in metabolic energy production and in the biosynthesis of cholesterol and fatty acids. The present studies suggest that the knockdown of these metabolic functions by RNAi is linked to an extension of life span and a decrease in fat content and body size.


Sign in / Sign up

Export Citation Format

Share Document