Angiotensin AT 1 receptor antagonism by losartan stimulates adipocyte browning via induction of apelin

Adipocyte browning appears to be a potential therapeutic strategy to combat obesity and related metabolic disorders. Recent studies have shown that apelin, an adipokine, stimulates adipocyte browning and has negative cross-talk with angiotensin II receptor type 1 (AT receptor) signaling. Here, we re...

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Bibliographic Details
Published in:The Journal of biological chemistry 2020-10, Vol.295 (44), p.14878
Main Authors: Kim, Dong Young, Choi, Mi Jin, Ko, Tae Kyung, Lee, Na Hyun, Kim, Ok-Hee, Cheon, Hyae Gyeong
Format: Article
Language:English
Subjects:
3T3-L1 Cells
Adipocytes, Brown - cytology
Adipocytes, Brown - drug effects
Adipocytes, Brown - metabolism
Angiotensin II Type 1 Receptor Blockers - pharmacology
Animals
Apelin - biosynthesis
Apelin - genetics
Cell Differentiation
Gene Knockdown Techniques
Losartan - pharmacology
Mice
Mice, Inbred C57BL
Receptor, Angiotensin, Type 1 - drug effects
RNA, Messenger - metabolism
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Summary:Adipocyte browning appears to be a potential therapeutic strategy to combat obesity and related metabolic disorders. Recent studies have shown that apelin, an adipokine, stimulates adipocyte browning and has negative cross-talk with angiotensin II receptor type 1 (AT receptor) signaling. Here, we report that losartan, a selective AT receptor antagonist, induces browning, as evidenced by an increase in browning marker expression, mitochondrial biogenesis, and oxygen consumption in murine adipocytes. In parallel, losartan up-regulated apelin expression, concomitant with increased phosphorylation of protein kinase B and AMP-activated protein kinase. However, the siRNA-mediated knockdown of apelin expression attenuated losartan-induced browning. Angiotensin II cotreatment also inhibited losartan-induced browning, suggesting that AT receptor antagonism-induced activation of apelin signaling may be responsible for adipocyte browning induced by losartan. The browning effects of losartan were confirmed using both C57BL/6J and ob/ob mice. Furthermore, apelin knockdown by adeno-associated virus carrying-apelin shRNA significantly inhibited losartan-induced adipocyte browning. In summary, these data suggested that AT receptor antagonism by losartan promotes the browning of white adipocytes via the induction of apelin expression. Therefore, apelin modulation may be an effective strategy for the treatment of obesity and its related metabolic disorders.
ISSN:1083-351X