Neuronatin regulates whole‐body metabolism: is thermogenesis involved?

Abstract Neuronatin (NNAT) was originally discovered in 1995 and labeled as a brain developmental gene due to its abundant expression in developing brains. Over the past 25 years, researchers have uncovered NNAT in other tissues; notably, the hypothalamus, pancreatic β‐cells, and adipocytes. Recent...

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Main Authors: Jessica L. Braun, Mia S. Geromella, Sophie I. Hamstra, Val A. Fajardo
Format: Article
Language:English
Published: Wiley 2020-10-01
Series:FASEB BioAdvances
Subjects:
Online Access:https://doi.org/10.1096/fba.2020-00052
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author Jessica L. Braun
Mia S. Geromella
Sophie I. Hamstra
Val A. Fajardo
author_facet Jessica L. Braun
Mia S. Geromella
Sophie I. Hamstra
Val A. Fajardo
author_sort Jessica L. Braun
collection DOAJ
description Abstract Neuronatin (NNAT) was originally discovered in 1995 and labeled as a brain developmental gene due to its abundant expression in developing brains. Over the past 25 years, researchers have uncovered NNAT in other tissues; notably, the hypothalamus, pancreatic β‐cells, and adipocytes. Recent evidence in these tissues indicates that NNAT plays a significant role in metabolism whereby it regulates food intake, insulin secretion, and adipocyte differentiation. Furthermore, genetic deletion of Nnat in mice lowers whole‐body energy expenditure and increases susceptibility to diet‐induced obesity and glucose intolerance; however, the underlying cellular mechanisms remain unknown. Based on its sequence homology with phospholamban, NNAT has a purported role in regulating the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) pump. However, NNAT also shares sequence homology with sarcolipin, which has the unique property of uncoupling the SERCA pump, increasing whole‐body energy expenditure and thus promoting adaptive thermogenesis in states of caloric excess or cold exposure. Thus, in this article, we discuss the accumulating evidence suggestive of NNAT’s role in whole‐body metabolic regulation, while highlighting its potential to mediate adaptive thermogenesis via SERCA uncoupling.
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spelling doaj.art-a4d84decad0746559eb60bab9f8341072022-12-22T00:18:01ZengWileyFASEB BioAdvances2573-98322020-10-0121057958610.1096/fba.2020-00052Neuronatin regulates whole‐body metabolism: is thermogenesis involved?Jessica L. Braun0Mia S. Geromella1Sophie I. Hamstra2Val A. Fajardo3Department of Kinesiology Brock University St. Catharines ON USADepartment of Kinesiology Brock University St. Catharines ON USADepartment of Kinesiology Brock University St. Catharines ON USADepartment of Kinesiology Brock University St. Catharines ON USAAbstract Neuronatin (NNAT) was originally discovered in 1995 and labeled as a brain developmental gene due to its abundant expression in developing brains. Over the past 25 years, researchers have uncovered NNAT in other tissues; notably, the hypothalamus, pancreatic β‐cells, and adipocytes. Recent evidence in these tissues indicates that NNAT plays a significant role in metabolism whereby it regulates food intake, insulin secretion, and adipocyte differentiation. Furthermore, genetic deletion of Nnat in mice lowers whole‐body energy expenditure and increases susceptibility to diet‐induced obesity and glucose intolerance; however, the underlying cellular mechanisms remain unknown. Based on its sequence homology with phospholamban, NNAT has a purported role in regulating the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) pump. However, NNAT also shares sequence homology with sarcolipin, which has the unique property of uncoupling the SERCA pump, increasing whole‐body energy expenditure and thus promoting adaptive thermogenesis in states of caloric excess or cold exposure. Thus, in this article, we discuss the accumulating evidence suggestive of NNAT’s role in whole‐body metabolic regulation, while highlighting its potential to mediate adaptive thermogenesis via SERCA uncoupling.https://doi.org/10.1096/fba.2020-00052brown adipocytecalciuminsulinleptinSERCA
spellingShingle Jessica L. Braun
Mia S. Geromella
Sophie I. Hamstra
Val A. Fajardo
Neuronatin regulates whole‐body metabolism: is thermogenesis involved?
FASEB BioAdvances
brown adipocyte
calcium
insulin
leptin
SERCA
title Neuronatin regulates whole‐body metabolism: is thermogenesis involved?
title_full Neuronatin regulates whole‐body metabolism: is thermogenesis involved?
title_fullStr Neuronatin regulates whole‐body metabolism: is thermogenesis involved?
title_full_unstemmed Neuronatin regulates whole‐body metabolism: is thermogenesis involved?
title_short Neuronatin regulates whole‐body metabolism: is thermogenesis involved?
title_sort neuronatin regulates whole body metabolism is thermogenesis involved
topic brown adipocyte
calcium
insulin
leptin
SERCA
url https://doi.org/10.1096/fba.2020-00052
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AT miasgeromella neuronatinregulateswholebodymetabolismisthermogenesisinvolved
AT sophieihamstra neuronatinregulateswholebodymetabolismisthermogenesisinvolved
AT valafajardo neuronatinregulateswholebodymetabolismisthermogenesisinvolved