| Create Account | login

login

Publication

Disrupted liver oxidative metabolism in glycine N-methyltransferase-deficient
mice is mitigated by dietary methionine restriction.

Authors	Rome FI, Hughey CC
Submitted By	Submitted Externally on 3/9/2022
Status	Published
Journal	Molecular metabolism
Year	2022
Date Published	2/1/2022
Volume : Pages	58 : 101452
PubMed Reference	35121169
Abstract	One-carbon metabolism is routinely dysregulated in nonalcoholic fatty liver disease. This includes decreased glycine N-methyltransferase (GNMT), a critical regulator of s-adenosylmethionine (SAM). Deletion of GNMT in mice increases SAM and promotes liver steatosis. Lower liver oxidative metabolism, as indicated by a decline in gluconeogenesis, citric acid cycle flux, and oxidative phosphorylation contributes to liver steatosis in GNMT-null mice; however, the extent to which higher SAM mediates this phenotype remains unclear. Here, we determined the SAM-dependent impairment in liver oxidative metabolism by loss of GNMT., GNMT knockout (KO) mice were fed a methionine-restricted diet to prevent increased SAM. 2H/13C metabolic flux analysis was performed in conscious, unrestrained mice to quantify liver nutrient fluxes. Metabolomics and high-resolution respirometry were used to quantify liver nutrient pool sizes and mitochondrial oxidative phosphorylation, respectively. Folic acid-supplemented and serine/glycine-deficient diets were used independently to further define the metabolic implications of perturbed one-carbon donor availability., Dietary methionine restriction prevented a 75-fold increase in SAM and a 53% rise in triacylglycerides in livers of KO mice. Dietary methionine restriction increased gluconeogenesis, independent of genotype, and restored cytochrome c oxidase respiratory function in KO mice. Citric acid cycle fluxes remained lower in KO mice irrespective of diet. Restricting dietary methionine abrogated markers of increased lipogenesis and folate cycle dysfunction in KO mice., The impaired liver oxidative metabolism following loss of GNMT is both dependent and independent of greater SAM availability. Lower in vivo citric acid cycle flux is independent of increased SAM. In contrast, gluconeogenesis and oxidative phosphorylation are negatively regulated by excess SAM. Lipid accumulation in livers of mice lacking GNMT is also linked to higher SAM.

Back to Top

Store Credentials?

MMPC-Live web resource – Terms of Use

Warranty disclaimer and copyright notice

THE MMPC-Live MAKES NO REPRESENTATION ABOUT THE SUITABILITY OR ACCURACY OF THE SOFTWARE OR DATA FOR ANY PURPOSE, AND MAKES NO WARRANTIES, EITHER EXPRESS OR IMPLIED, INCLUDING MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR THAT THE USE OF THE SOFTWARE OR DATA WILL NOT INFRINGE ANY THIRD PARTY PATENTS, COPYRIGHTS, TRADEMARKS, OR OTHER RIGHTS. THE SOFTWARE AND DATA ARE PROVIDED "AS IS".

The Mouse Metabolic Phenotyping Centers (MMPC-Live) is an NIDDK funded consortium and adheres to the NIH Data Sharing Policy.

MMPC-Live clients make their data freely available whereby MMPC-Live users may freely build upon, enhance and reuse those data for any purpose without restriction. Scholarly citation norms must be followed for content reuse. Please acknowledge the MMPC-Live using the following text: 'The MMPC-Live data used in this manuscript was supported by the NIDDK National Mouse Metabolic Phenotyping Centers (MMPC-Live, RRID:SCR_008997, www.mmpc.org)'. To cite specific MMPC-Live centers, please use the appropriate RRID available from the MMPC-Live website (https://www.mmpc.org/shared/centers.aspx).

Please note that the acknowledgment text includes a Research Resource Identifier (RRID) for the MMPC-Live CU and Centers. Reproducibility is one of the corner stones of effective, open and transparent biomedical published research. However, too often, resources (e.g. model organisms, antibodies, and tools) are not reported with adequate detail to ensure others can replicate or expand upon the published results. The Research Resource Identification Initiative (#RII) seeks to change these limitations in reporting by the use of unique Research Resource Identifiers (RRIDs). This initiative is designed to encourage authors to provide identification of the types of resources used in their research by adding a globally unique accession number to the resources described in the their manuscripts. These identifiers, called RRIDs, will allow authors to cite the resources that they use in their manuscripts. RRIDs allow for easy tracking of all papers that have used the same resource making it easy to access how the same resources works in other scenarios.

It is expected that MMPC-Live users follow scholarly citation norms, giving credit to fellow scholars when accessing/using protocols and data, including data derived by MMPC-Live (such as summary data) and any plots, tables or screenshots depicting those data.

It is possible for invalid or incomplete results to be presented on the MMPC-Live web site due to software bugs, data problems, or artifacts of human error. Data sets are not necessarily static; we reserve the right to post corrections and updates as needed.

Prohibited use. Data contributors and data users may not use MMPC-Live in any unlawful manner, or in any manner that could impair MMPC-Live services, security or functionality. Automated usage (webcrawlers and similar) must observe each page's "meta robots" html tags and space requests by ≥ 2 seconds. We reserve the right to block any IP associated with what we consider to be excessive or abusive usage patterns, and/or to take any action we deem necessary.

MMPC-Live is a National Institutes of Health-sponsored resource that provides experimental testing services to scientists studying diabetes, obesity, diabetic complications, and other metabolic diseases in mice.

Menu

Home

Contact

About MMPC

Animal Husbandry

Tests Data

Search Data

Analysis

Clients

MMPC Centers

Newsletter

Interested in receiving MMPC News?

Mouse Phenotyping
@NationalMMPC

2017 National MMPC. All Rights Reserved.