Journal article
ATF4 expression in thermogenic adipocytes is required for cold-induced thermogenesis in mice via FGF21-independent mechanisms
Scientific reports, Vol.14(1), 1563
01/18/2024
DOI: 10.1038/s41598-024-52004-8
PMCID: PMC10796914
PMID: 38238383
Abstract
In brown adipose tissue (BAT), short-term cold exposure induces the activating transcription factor 4 (ATF4), and its downstream target fibroblast growth factor 21 (FGF21). Induction of ATF4 in BAT in response to mitochondrial stress is required for thermoregulation, partially by increasing FGF21 expression. In the present study, we tested the hypothesis that Atf4 and Fgf21 induction in BAT are both required for BAT thermogenesis under physiological stress by generating mice selectively lacking either Atf4 (ATF4 BKO) or Fgf21 (FGF21 BKO) in UCP1-expressing adipocytes. After 3 days of cold exposure, core body temperature was significantly reduced in ad-libitum-fed ATF4 BKO mice, which correlated with Fgf21 downregulation in brown and beige adipocytes, and impaired browning of white adipose tissue. Conversely, despite having reduced browning, FGF21 BKO mice had preserved core body temperature after cold exposure. Mechanistically, ATF4, but not FGF21, regulates amino acid import and metabolism in response to cold, likely contributing to BAT thermogenic capacity under ad libitum-fed conditions. Importantly, under fasting conditions, both ATF4 and FGF21 were required for thermogenesis in cold-exposed mice. Thus, ATF4 regulates BAT thermogenesis under fed conditions likely in a FGF21-independent manner, in part via increased amino acid uptake and metabolism.
Details
- Title: Subtitle
- ATF4 expression in thermogenic adipocytes is required for cold-induced thermogenesis in mice via FGF21-independent mechanisms
- Creators
- Sarah H Bjorkman - University of IowaAlex Marti - University of IowaJayashree Jena - University of IowaLuis Miguel García-Peña - University of IowaEric T Weatherford - University of IowaKevin Kato - University of IowaJivan Koneru - University of IowaJason Chen - University of IowaAyushi Sood - University of IowaMatthew J Potthoff - University of IowaChristopher M Adams - Mayo ClinicE Dale Abel - University of California, Los AngelesRenata O Pereira - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.14(1), 1563
- DOI
- 10.1038/s41598-024-52004-8
- PMID
- 38238383
- PMCID
- PMC10796914
- NLM abbreviation
- Sci Rep
- eISSN
- 2045-2322
- Grant note
- HL112413 / NIH HHS 1R25GM116686 / NIH HHS HL127764 / NIH HHS DK125405 / NIH HHS T32DK112751 / NIH HHS
- Language
- English
- Date published
- 01/18/2024
- Academic Unit
- Iowa Neuroscience Institute; Orthopedics and Rehabilitation; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984548297702771
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