Dataset Information

Is REDD1 a Metabolic Eminence Grise?

ABSTRACT: Regulated in development and DNA damage response 1 (REDD1) has been functionally linked to the control of diverse cellular processes due, at least in part, to its ability to repress mammalian or mechanistic Target of Rapamycin (mTOR) Complex-1 (mTORC1), a key protein complex controlled by hormonal and nutrient cues. Notably, emerging evidence suggests that REDD1 also regulates several pathways involved in modulating energy balance and metabolism. Herein, we discuss evidence implicating REDD1 as a key modulator of insulin action and metabolic function, including its potential contribution to mitochondrial biology and pancreatic islet function. Collectively, the available evidence suggests that REDD1 has a more prominent role in energy homeostasis than was previously thought, and implicates REDD1 as a potential therapeutic target for treatment of metabolic disorders.

SUBMITTER: Lipina C

PROVIDER: S-EPMC5119498 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Is REDD1 a Metabolic Éminence Grise?

Lipina Christopher C Hundal Harinder S HS

Trends in endocrinology and metabolism: TEM 20160906 12

Regulated in development and DNA damage response 1 (REDD1) has been functionally linked to the control of diverse cellular processes due, at least in part, to its ability to repress mammalian or mechanistic Target of Rapamycin (mTOR) Complex-1 (mTORC1), a key protein complex controlled by hormonal and nutrient cues. Notably, emerging evidence suggests that REDD1 also regulates several pathways involved in modulating energy balance and metabolism. Herein, we discuss evidence implicating REDD1 as ...[more]

PMID: 27613400

Similar Datasets

Project description:Cancer cachexia is a wasting disorder associated with advanced cancer that contributes to mortality. Cachexia is characterized by involuntary loss of body weight and muscle weakness that affects physical function. Regulated in DNA damage and development 1 (REDD1) is a stress-response protein that is transcriptionally upregulated in muscle during wasting conditions and inhibits mechanistic target of rapamycin complex 1 (mTORC1). C2C12 myotubes treated with Lewis lung carcinoma (LLC)-conditioned media increased REDD1 mRNA expression and decreased myotube diameter. To investigate the role of REDD1 in cancer cachexia, we inoculated 12-wk-old male wild-type or global REDD1 knockout (REDD1 KO) mice with LLC cells and euthanized 28 days later. Wild-type mice had increased skeletal muscle REDD1 expression, and REDD1 deletion prevented loss of body weight and lean tissue mass but not fat mass. We found that REDD1 deletion attenuated loss of individual muscle weights and loss of myofiber cross-sectional area. We measured markers of the Akt/mTORC1 pathway and found that, unlike wild-type mice, phosphorylation of both Akt and 4E-BP1 was maintained in the muscle of REDD1 KO mice after LLC inoculation, suggesting that loss of REDD1 is beneficial in maintaining mTORC1 activity in mice with cancer cachexia. We measured Foxo3a phosphorylation as a marker of the ubiquitin proteasome pathway and autophagy and found that REDD1 deletion prevented dephosphorylation of Foxo3a in muscles from cachectic mice. Our data provide evidence that REDD1 plays an important role in cancer cachexia through the regulation of both protein synthesis and protein degradation pathways.NEW & NOTEWORTHY Cancer cachexia is a debilitating and lethal consequence of many advanced cancers. REDD1, a negative regulator of mTORC1 activity, is an emerging target in cachexia. Our data show that skeletal muscle REDD1 expression is increased in LLC-induced cancer cachexia. Mice lacking REDD1 have attenuated skeletal muscle atrophy that is likely due to maintaining both protein synthesis and inhibiting protein degradation.

Dataset Information

Is REDD1 a Metabolic Eminence Grise?

Publications

Is REDD1 a Metabolic Éminence Grise?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets