Impaired BCAA catabolism in adipose tissues promotes age-associated metabolic derangement

Hye Sook Han, Eunyong Ahn, Eun Seo Park, Tom Huh, Seri Choi, Yongmin Kwon, Byeong Hun Choi, Jueun Lee, Yoon Ha Choi, Yujin L. Jeong, Gwang Bin Lee, Minji Kim, Je Kyung Seong, Hyun Mu Shin, Hang Rae Kim, Myeong Hee Moon, Jong Kyoung Kim, Geum Sook Hwang, Seung Hoi Koo

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Adipose tissues are central in controlling metabolic homeostasis and failure in their preservation is associated with age-related metabolic disorders. The exact role of mature adipocytes in this phenomenon remains elusive. Here we describe the role of adipose branched-chain amino acid (BCAA) catabolism in this process. We found that adipocyte-specific Crtc2 knockout protected mice from age-associated metabolic decline. Multiomics analysis revealed that BCAA catabolism was impaired in aged visceral adipose tissues, leading to the activation of mechanistic target of rapamycin complex (mTORC1) signaling and the resultant cellular senescence, which was restored by Crtc2 knockout in adipocytes. Using single-cell RNA sequencing analysis, we found that age-associated decline in adipogenic potential of visceral adipose tissues was reinstated by Crtc2 knockout, via the reduction of BCAA–mTORC1 senescence-associated secretory phenotype axis. Collectively, we propose that perturbation of BCAA catabolism by CRTC2 is critical in instigating age-associated remodeling of adipose tissue and the resultant metabolic decline in vivo.

Original languageEnglish
Pages (from-to)982-1000
Number of pages19
JournalNature Aging
Issue number8
Publication statusPublished - 2023 Aug

Bibliographical note

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Ageing
  • Geriatrics and Gerontology


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