A negative feedback loop between TET2 and leptin in adipocyte regulates body weight

Qin Zeng, Jianfeng Song, Xiaoxiao Sun, Dandan Wang, Xiyan Liao, Yujin Ding, Wanyu Hu, Yayi Jiao, Wuqian Mai, Wufuer Aini, Fanqi Wang, Hui Zhou, Limin Xie, Ying Mei, Yuan Tang, Zhiguo Xie, Haijing Wu, Wei Liu and Tuo Deng ()
Additional contact information
Qin Zeng: The Second Xiangya Hospital of Central South University
Jianfeng Song: The Second Xiangya Hospital of Central South University
Xiaoxiao Sun: The Second Xiangya Hospital of Central South University
Dandan Wang: The Second Xiangya Hospital of Central South University
Xiyan Liao: The Second Xiangya Hospital of Central South University
Yujin Ding: The Second Xiangya Hospital of Central South University
Wanyu Hu: The Second Xiangya Hospital of Central South University
Yayi Jiao: The Second Xiangya Hospital of Central South University
Wuqian Mai: The Second Xiangya Hospital of Central South University
Wufuer Aini: The Second Xiangya Hospital of Central South University
Fanqi Wang: The Second Xiangya Hospital of Central South University
Hui Zhou: The Second Xiangya Hospital of Central South University
Limin Xie: The Second Xiangya Hospital of Central South University
Ying Mei: The Second Xiangya Hospital of Central South University
Yuan Tang: The Second Xiangya Hospital of Central South University
Zhiguo Xie: The Second Xiangya Hospital of Central South University
Haijing Wu: The Second Xiangya Hospital of Central South University
Wei Liu: The Second Xiangya Hospital of Central South University
Tuo Deng: The Second Xiangya Hospital of Central South University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Ten-eleven translocation (TET) 2 is an enzyme that catalyzes DNA demethylation to regulate gene expression by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, functioning as an essential epigenetic regulator in various biological processes. However, the regulation and function of TET2 in adipocytes during obesity are poorly understood. In this study, we demonstrate that leptin, a key adipokine in mammalian energy homeostasis regulation, suppresses adipocyte TET2 levels via JAK2-STAT3 signaling. Adipocyte Tet2 deficiency protects against high-fat diet-induced weight gain by reducing leptin levels and further improving leptin sensitivity in obese male mice. By interacting with C/EBPα, adipocyte TET2 increases the hydroxymethylcytosine levels of the leptin gene promoter, thereby promoting leptin gene expression. A decrease in adipose TET2 is associated with obesity-related hyperleptinemia in humans. Inhibition of TET2 suppresses the production of leptin in mature human adipocytes. Our findings support the existence of a negative feedback loop between TET2 and leptin in adipocytes and reveal a compensatory mechanism for the body to counteract the metabolic dysfunction caused by obesity.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-46783-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46783-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-46783-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().