Abstract:
:Adipose tissue dysfunction is causally implicated in the impaired metabolic homeostasis associated with obesity; however, detailed mechanisms underlying dysregulated adipocyte functions in obesity remain to be elucidated. Here we searched for genes that provide a previously unknown mechanism in adipocyte metabolic functions and identified family with sequence similarity 13, member A (Fam13a) as a factor that modifies insulin signal cascade in adipocytes. Fam13a was highly expressed in adipose tissue, predominantly in mature adipocytes, and its expression was substantially reduced in adipose tissues of obese compared with lean mice. We revealed that Fam13a accentuated insulin signaling by recruiting protein phosphatase 2A with insulin receptor substrate 1 (IRS1), leading to protection of IRS1 from proteasomal degradation. We further demonstrated that genetic loss of Fam13a exacerbated obesity-related metabolic disorders, while targeted activation of Fam13a in adipocytes ameliorated it in association with altered adipose tissue insulin sensitivity in mice. Our data unveiled a previously unknown mechanism in the regulation of adipocyte insulin signaling by Fam13a and identified its significant role in systemic metabolic homeostasis, shedding light on Fam13a as a pharmacotherapeutic target to treat obesity-related metabolic disorders.
journal_name
Proc Natl Acad Sci U S Aauthors
Wardhana DA,Ikeda K,Barinda AJ,Nugroho DB,Qurania KR,Yagi K,Miyata K,Oike Y,Hirata KI,Emoto Ndoi
10.1073/pnas.1720475115subject
Has Abstractpub_date
2018-02-13 00:00:00pages
1529-1534issue
7eissn
0027-8424issn
1091-6490pii
1720475115journal_volume
115pub_type
杂志文章abstract::Plant soil specialists contribute greatly to global diversity; however, the ecoevolutionary forces responsible for generating this diversity are poorly understood. We integrate molecular phylogenies with descriptive and experimental ecological data, creating a powerful framework with which to elucidate forces driving ...
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