OPA1 deletion in brown adipose tissue Improves thermoregulation and systemic metabolism via FGF21

Renata O Pereira; Alex Marti; Angela Crystal Olvera; Satya Murthy Tadinada; Sarah Hartwick Bjorkman; Eric Thomas Weatherford; Donald A Morgan; Michael Westphal; Pooja H Patel; Ana Karina Kirby; Rana Hewezi; William Bùi Trần; Luis Miguel García-Peña; Rhonda A Souvenir; Monika Mittal; Christopher M Adams; Kamal Rahmouni; Matthew J Potthoff; E Dale Abel

doi:10.7554/eLife.66519

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OPA1 deletion in brown adipose tissue Improves thermoregulation and systemic metabolism via FGF21

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OPA1 deletion in brown adipose tissue Improves thermoregulation and systemic metabolism via FGF21

Renata O Pereira, Alex Marti, Angela Crystal Olvera, Satya Murthy Tadinada, Sarah Hartwick Bjorkman, Eric Thomas Weatherford, Donald A Morgan, Michael Westphal, Pooja H Patel, Ana Karina Kirby, …

eLife, Vol.10, e66519

05/04/2021

DOI: 10.7554/eLife.66519

PMID: 33944779

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Abstract

Adrenergic stimulation of brown adipocytes alters mitochondrial dynamics, including the mitochondrial fusion protein optic atrophy 1 (OPA1). However, direct mechanisms linking OPA1 to brown adipose tissue (BAT) physiology are incompletely understood. We utilized a mouse model of selective OPA1 deletion in BAT (OPA1 BAT KO) to investigate the role of OPA1 in thermogenesis. OPA1 is required for cold-induced activation of thermogenic genes in BAT. Unexpectedly, OPA1 deficiency induced fibroblast growth factor 21 (FGF21) as a BATokine in an activating transcription factor 4 (ATF4)-dependent manner. BAT-derived FGF21 mediates an adaptive response, by inducing browning of white adipose tissue, increasing resting metabolic rates, and improving thermoregulation. However, mechanisms independent of FGF21, but dependent on ATF4 induction, promote resistance to diet-induced obesity in OPA1 BAT KO mice. These findings uncover a homeostatic mechanism of BAT-mediated metabolic protection governed in part by an ATF4-FGF21 axis, that is activated independently of BAT thermogenic function.

Details

Title: Subtitle: OPA1 deletion in brown adipose tissue Improves thermoregulation and systemic metabolism via FGF21
Creators: Renata O Pereira - Internal Medicine, University of Iowa, Iowa City, United States
Alex Marti - Internal Medicine, University of Iowa, Iowa City, United States
Angela Crystal Olvera - Internal Medicine, University of Iowa, Iowa City, United States
Satya Murthy Tadinada - Internal Medicine, University of Iowa, Iowa City, United States
Sarah Hartwick Bjorkman - Obstetrics and Gynecology, University of Iowa, Iowa City, United States
Eric Thomas Weatherford - Internal Medicine, University of Iowa, Iowa City, United States
Donald A Morgan - Neuroscience and Pharmacology, University of Iowa, Iowa City, United States
Michael Westphal - Internal Medicine, University of Iowa, Iowa City, United States
Pooja H Patel - Internal Medicine, University of Iowa, Iowa City, United States
Ana Karina Kirby - Internal Medicine, University of Iowa, Iowa City, United States
Rana Hewezi - Internal Medicine, University of Iowa, Iowa City, United States
William Bùi Trần - Internal Medicine, University of Iowa, Iowa City, United States
Luis Miguel García-Peña - Internal Medicine, University of Iowa, Iowa City, United States
Rhonda A Souvenir - Internal Medicine, University of Iowa, Iowa City, United States
Monika Mittal - Internal Medicine, University of Iowa, Iowa City, United States
Christopher M Adams - Department of Internal Medicine, University of Iowa, Iowa City, United States
Kamal Rahmouni - Pharmacology, University of Iowa, Iowa City, United States
Matthew J Potthoff - Pharmacology, University of Iowa, Iowa City, United States
E Dale Abel - Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, University of Iowa, Iowa City, United States
Resource Type: Journal article
Publication Details: eLife, Vol.10, e66519
DOI: 10.7554/eLife.66519
PMID: 33944779
NLM abbreviation: Elife
ISSN: 2050-084X
eISSN: 2050-084X
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: HL127764; DOI: 10.13039/100000002, name: National Institutes of Health, award: HL112413; DOI: 10.13039/100000968, name: American Heart Association, award: 20SFRN35120123; DOI: 10.13039/100000968, name: American Heart Association, award: 15SDG25710438; DOI: 10.13039/100000002, name: National Institutes of Health, award: DK125405; DOI: 10.13039/100000002, name: National Institutes of Health, award: T32DK112751; DOI: 10.13039/100000002, name: National Institutes of Health, award: 1R25GM116686
Language: English
Date published: 05/04/2021
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute; Orthopedics and Rehabilitation; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984071989802771

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