2026-10-14T04:21:01Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34031951 2026-09-30T11:42:17Z category_4 category_7 category_12 category_14 category_16 category_19 category_873 category_64 portal_87 item_type_3 month_year_09_2026

Pharmacological inhibition of CLPP stabilizes LETMD1 to boost thermogenesis and alleviate obesity Huiwen Yuan (10138193) Yuqing Deng (1649710) Jingang Wang (242580) Bing Luan (14209559) Zhen-Ning Zhang (16884519) Biochemistry Medicine Cell Biology Molecular Biology Physiology Pharmacology Chemical Sciences not elsewhere classified Cancer Obesity adipose thermogenesis mitochondrial proteostasis CLPP LETMD1 <p>Obesity poses a severe global health burden, and activating adipose thermogenesis offers a promising therapeutic avenue. However, the contribution of mitochondrial proteostasis to thermogenic regulation remains elusive. Here, we identify mitochondrial protease CLPP as a negative regulator of adipose thermogenesis. Pharmacological suppression of CLPP activity enhances thermogenic programmes in adipocytes. Mechanistically, CLPP interacts with LETMD1 and promotes its degradation at the post-translational level, while LETMD1 stabilization is required for the thermogenic effects induced by CLPP suppression. <i>In vivo</i>, pharmacological suppression of CLPP activity using hinokiflavone significantly enhances energy expenditure, attenuates weight gain, and improves insulin sensitivity in obese mice. Collectively, our study identifies a CLPP–LETMD1 regulatory axis that regulates adipose thermogenesis and highlights CLPP suppression as a potential therapeutic strategy for obesity intervention.</p> 2026-09-30T11:42:17Z Dataset Dataset 10.6084/m9.figshare.34031951.v1 https://figshare.com/articles/dataset/Pharmacological_inhibition_of_CLPP_stabilizes_LETMD1_to_boost_thermogenesis_and_alleviate_obesity/34031951 CC BY 4.0