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Nipsnap1—A regulatory factor required for long-term maintenance of non-shivering thermogenesis
OBJECTIVE: The activation of non-shivering thermogenesis (NST) has strong potential to combat obesity and metabolic disease. The activation of NST however is extremely temporal and the mechanisms surrounding how the benefits of NST are sustained once fully activated, remain unexplored. The objective...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404556/ https://www.ncbi.nlm.nih.gov/pubmed/37423391 http://dx.doi.org/10.1016/j.molmet.2023.101770 |
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author | Liu, Yang Qu, Yue Cheng, Chloe Tsai, Pei-Yin Edwards, Kaydine Xue, Siwen Pandit, Supriya Eguchi, Sakura Sanghera, Navneet Barrow, Joeva J. |
author_facet | Liu, Yang Qu, Yue Cheng, Chloe Tsai, Pei-Yin Edwards, Kaydine Xue, Siwen Pandit, Supriya Eguchi, Sakura Sanghera, Navneet Barrow, Joeva J. |
author_sort | Liu, Yang |
collection | PubMed |
description | OBJECTIVE: The activation of non-shivering thermogenesis (NST) has strong potential to combat obesity and metabolic disease. The activation of NST however is extremely temporal and the mechanisms surrounding how the benefits of NST are sustained once fully activated, remain unexplored. The objective of this study is to investigate the role of 4-Nitrophenylphosphatase Domain and Non-Neuronal SNAP25-Like 1 (Nipsnap1) in NST maintenance, which is a critical regulator identified in this study. METHODS: The expression of Nipsnap1 was profiled by immunoblotting and RT-qPCR. We generated Nipsnap1 knockout mice (N1–KO) and investigated the function of Nipsnap1 in NST maintenance and whole-body metabolism using whole body respirometry analyses. We evaluate the metabolic regulatory role of Nipsnap1 using cellular and mitochondrial respiration assay. RESULTS: Here, we show Nipsnap1 as a critical regulator of long-term thermogenic maintenance in brown adipose tissue (BAT). Nipsnap1 localizes to the mitochondrial matrix and increases its transcript and protein levels in response to both chronic cold and β3 adrenergic signaling. We demonstrated that these mice are unable to sustain activated energy expenditure and have significantly lower body temperature in the face of an extended cold challenge. Furthermore, when mice are exposed to the pharmacological β3 agonist CL 316, 243, the N1–KO mice exhibit significant hyperphagia and altered energy balance. Mechanistically, we demonstrate that Nipsnap1 integrates with lipid metabolism and BAT-specific ablation of Nipsnap1 leads to severe defects in beta-oxidation capacity when exposed to a cold environmental challenge. CONCLUSION: Our findings identify Nipsnap1 as a potent regulator of long-term NST maintenance in BAT. |
format | Online Article Text |
id | pubmed-10404556 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-104045562023-08-08 Nipsnap1—A regulatory factor required for long-term maintenance of non-shivering thermogenesis Liu, Yang Qu, Yue Cheng, Chloe Tsai, Pei-Yin Edwards, Kaydine Xue, Siwen Pandit, Supriya Eguchi, Sakura Sanghera, Navneet Barrow, Joeva J. Mol Metab Original Article OBJECTIVE: The activation of non-shivering thermogenesis (NST) has strong potential to combat obesity and metabolic disease. The activation of NST however is extremely temporal and the mechanisms surrounding how the benefits of NST are sustained once fully activated, remain unexplored. The objective of this study is to investigate the role of 4-Nitrophenylphosphatase Domain and Non-Neuronal SNAP25-Like 1 (Nipsnap1) in NST maintenance, which is a critical regulator identified in this study. METHODS: The expression of Nipsnap1 was profiled by immunoblotting and RT-qPCR. We generated Nipsnap1 knockout mice (N1–KO) and investigated the function of Nipsnap1 in NST maintenance and whole-body metabolism using whole body respirometry analyses. We evaluate the metabolic regulatory role of Nipsnap1 using cellular and mitochondrial respiration assay. RESULTS: Here, we show Nipsnap1 as a critical regulator of long-term thermogenic maintenance in brown adipose tissue (BAT). Nipsnap1 localizes to the mitochondrial matrix and increases its transcript and protein levels in response to both chronic cold and β3 adrenergic signaling. We demonstrated that these mice are unable to sustain activated energy expenditure and have significantly lower body temperature in the face of an extended cold challenge. Furthermore, when mice are exposed to the pharmacological β3 agonist CL 316, 243, the N1–KO mice exhibit significant hyperphagia and altered energy balance. Mechanistically, we demonstrate that Nipsnap1 integrates with lipid metabolism and BAT-specific ablation of Nipsnap1 leads to severe defects in beta-oxidation capacity when exposed to a cold environmental challenge. CONCLUSION: Our findings identify Nipsnap1 as a potent regulator of long-term NST maintenance in BAT. Elsevier 2023-07-07 /pmc/articles/PMC10404556/ /pubmed/37423391 http://dx.doi.org/10.1016/j.molmet.2023.101770 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Liu, Yang Qu, Yue Cheng, Chloe Tsai, Pei-Yin Edwards, Kaydine Xue, Siwen Pandit, Supriya Eguchi, Sakura Sanghera, Navneet Barrow, Joeva J. Nipsnap1—A regulatory factor required for long-term maintenance of non-shivering thermogenesis |
title | Nipsnap1—A regulatory factor required for long-term maintenance of non-shivering thermogenesis |
title_full | Nipsnap1—A regulatory factor required for long-term maintenance of non-shivering thermogenesis |
title_fullStr | Nipsnap1—A regulatory factor required for long-term maintenance of non-shivering thermogenesis |
title_full_unstemmed | Nipsnap1—A regulatory factor required for long-term maintenance of non-shivering thermogenesis |
title_short | Nipsnap1—A regulatory factor required for long-term maintenance of non-shivering thermogenesis |
title_sort | nipsnap1—a regulatory factor required for long-term maintenance of non-shivering thermogenesis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404556/ https://www.ncbi.nlm.nih.gov/pubmed/37423391 http://dx.doi.org/10.1016/j.molmet.2023.101770 |
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