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Male Mice Lacking NLRX1 Are Partially Protected From High-Fat Diet–Induced Hyperglycemia
Nod-like receptor (NLR)X1 is an NLR family protein that localizes to the mitochondrial matrix and modulates reactive oxygen species production, possibly by directly interacting with the electron transport chain. Recent work demonstrated that cells lacking NLRX1 have higher oxygen consumption but low...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Endocrine Society
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855099/ https://www.ncbi.nlm.nih.gov/pubmed/29577109 http://dx.doi.org/10.1210/js.2017-00360 |
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author | Costford, Sheila R Tattoli, Ivan Duan, Francis T Volchuk, Allen Klip, Amira Philpott, Dana J Woo, Minna Girardin, Stephen E |
author_facet | Costford, Sheila R Tattoli, Ivan Duan, Francis T Volchuk, Allen Klip, Amira Philpott, Dana J Woo, Minna Girardin, Stephen E |
author_sort | Costford, Sheila R |
collection | PubMed |
description | Nod-like receptor (NLR)X1 is an NLR family protein that localizes to the mitochondrial matrix and modulates reactive oxygen species production, possibly by directly interacting with the electron transport chain. Recent work demonstrated that cells lacking NLRX1 have higher oxygen consumption but lower levels of adenosine triphosphate, suggesting that NLRX1 might prevent uncoupling of oxidative phosphorylation. We therefore hypothesized that NLRX1 might regulate whole-body energy metabolism through its effect on mitochondria. Male NLRX1 whole-body knockout (KO) mice and wild-type (WT) C57BL/6N controls were fed a low-fat or a high-fat (HF) diet for 16 weeks from weaning. Contrary to this hypothesis, there were no differences in body weight, adiposity, energy intake, or energy expenditure between HF-fed KO and WT mice, but instead HF KO mice were partially protected from the development of diet-induced hyperglycemia. Additionally, HF KO mice did not present with hyperinsulinemia during the glucose tolerance test, as did HF WT mice. There were no genotype differences in insulin tolerance, which led us to consider a pancreatic phenotype. Histology revealed that KO mice were protected from HF-induced pancreatic lipid accumulation, suggesting a potential role for NLRX1 in pancreatic dysfunction during the development diet-induced type 2 diabetes mellitus. Hence, NLRX1 depletion partially protects against postabsorptive hyperglycemia in obesity that may be linked to the prevention of pancreatic lipid accumulation. Although the actual mechanisms restoring glucose and insulin dynamics remain unknown, NLRX1 emerges as a potentially interesting target to inhibit for the prevention of type 2 diabetes mellitus. |
format | Online Article Text |
id | pubmed-5855099 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Endocrine Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-58550992018-03-23 Male Mice Lacking NLRX1 Are Partially Protected From High-Fat Diet–Induced Hyperglycemia Costford, Sheila R Tattoli, Ivan Duan, Francis T Volchuk, Allen Klip, Amira Philpott, Dana J Woo, Minna Girardin, Stephen E J Endocr Soc Research Articles Nod-like receptor (NLR)X1 is an NLR family protein that localizes to the mitochondrial matrix and modulates reactive oxygen species production, possibly by directly interacting with the electron transport chain. Recent work demonstrated that cells lacking NLRX1 have higher oxygen consumption but lower levels of adenosine triphosphate, suggesting that NLRX1 might prevent uncoupling of oxidative phosphorylation. We therefore hypothesized that NLRX1 might regulate whole-body energy metabolism through its effect on mitochondria. Male NLRX1 whole-body knockout (KO) mice and wild-type (WT) C57BL/6N controls were fed a low-fat or a high-fat (HF) diet for 16 weeks from weaning. Contrary to this hypothesis, there were no differences in body weight, adiposity, energy intake, or energy expenditure between HF-fed KO and WT mice, but instead HF KO mice were partially protected from the development of diet-induced hyperglycemia. Additionally, HF KO mice did not present with hyperinsulinemia during the glucose tolerance test, as did HF WT mice. There were no genotype differences in insulin tolerance, which led us to consider a pancreatic phenotype. Histology revealed that KO mice were protected from HF-induced pancreatic lipid accumulation, suggesting a potential role for NLRX1 in pancreatic dysfunction during the development diet-induced type 2 diabetes mellitus. Hence, NLRX1 depletion partially protects against postabsorptive hyperglycemia in obesity that may be linked to the prevention of pancreatic lipid accumulation. Although the actual mechanisms restoring glucose and insulin dynamics remain unknown, NLRX1 emerges as a potentially interesting target to inhibit for the prevention of type 2 diabetes mellitus. Endocrine Society 2018-02-21 /pmc/articles/PMC5855099/ /pubmed/29577109 http://dx.doi.org/10.1210/js.2017-00360 Text en Copyright © 2018 Endocrine Society https://creativecommons.org/licenses/by-nc-nd/4.0/ This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Articles Costford, Sheila R Tattoli, Ivan Duan, Francis T Volchuk, Allen Klip, Amira Philpott, Dana J Woo, Minna Girardin, Stephen E Male Mice Lacking NLRX1 Are Partially Protected From High-Fat Diet–Induced Hyperglycemia |
title | Male Mice Lacking NLRX1 Are Partially Protected From High-Fat Diet–Induced Hyperglycemia |
title_full | Male Mice Lacking NLRX1 Are Partially Protected From High-Fat Diet–Induced Hyperglycemia |
title_fullStr | Male Mice Lacking NLRX1 Are Partially Protected From High-Fat Diet–Induced Hyperglycemia |
title_full_unstemmed | Male Mice Lacking NLRX1 Are Partially Protected From High-Fat Diet–Induced Hyperglycemia |
title_short | Male Mice Lacking NLRX1 Are Partially Protected From High-Fat Diet–Induced Hyperglycemia |
title_sort | male mice lacking nlrx1 are partially protected from high-fat diet–induced hyperglycemia |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855099/ https://www.ncbi.nlm.nih.gov/pubmed/29577109 http://dx.doi.org/10.1210/js.2017-00360 |
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