Nardilysin in adipocytes regulates UCP1 expression and body temperature homeostasis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2022-03-02

AUTHORS

Sayaka Saijo, Mikiko Ohno, Hirotaka Iwasaki, Shintaro Matsuda, Kiyoto Nishi, Yoshinori Hiraoka, Natsuki Ide, Takeshi Kimura, Eiichiro Nishi

ABSTRACT

Brown adipose tissue (BAT) dissipates chemical energy as heat through uncoupling protein 1 (UCP1). The induction of mitochondrial reactive oxygen species (ROS) in BAT was recently identified as a mechanism that supports UCP1-dependent thermogenesis. We previously demonstrated that nardilysin (NRDC) plays critical roles in body temperature homeostasis. Global NRDC-deficient (Nrdc–/–) mice show hypothermia due to a lower set point for body temperature, whereas BAT thermogenesis at room temperature (RT) is enhanced mainly to compensate for poor thermal insulation. To examine the primary role of NRDC in BAT thermogenesis, we generated adipocyte-specific NRDC-deficient (Adipo-KO) mice by mating Nrdc floxed (Nrdcflox/flox) mice with adiponectin-Cre mice. Adipo-KO mice showed hyperthermia at both RT and thermoneutrality. They were also more cold-tolerant than Nrdcflox/flox mice. However, UCP1 mRNA levels were significantly lower in Adipo-KO BAT at RT, thermoneutrality, and 4 °C, whereas no significant differences were observed in UCP1 protein levels at RT and 4 °C. We examined the protein stability of UCP1 using the cycloheximide chase assay and found that NRDC negatively regulated its stability via the ubiquitin–proteasome pathway. NRDC may be also involved in ROS-mediated in vivo thermogenesis because the inhibitory effects of N-acetyl cysteine, an ROS scavenger, on β3 agonist-induced thermogenesis were stronger in Adipo-KO mice. Collectively, the present results demonstrate that NRDC in BAT controls adaptive thermogenesis and body temperature homeostasis possibly via the regulation of UCP1 protein stability and ROS levels. More... »

PAGES

3449

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-022-07379-x

DOI

http://dx.doi.org/10.1038/s41598-022-07379-x

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35236897


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69 mRNA levels
70 mechanism
71 mice
72 mitochondrial reactive oxygen species
73 nardilysin
74 oxygen species
75 pathway
76 point
77 poor thermal insulation
78 present results
79 primary role
80 protein 1
81 protein levels
82 protein stability
83 reactive oxygen species
84 regulation
85 results
86 role
87 room temperature
88 scavengers
89 set point
90 significant differences
91 species
92 stability
93 temperature
94 temperature homeostasis
95 thermal insulation
96 thermogenesis
97 thermoneutrality
98 tissue
99 ubiquitin-proteasome pathway
100 vivo thermogenesis
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