Defective brown adipose tissue thermogenesis and impaired glucose metabolism in mice lacking Letmd1

Kyung Mi Choi, Jung Hak Kim, Xiangmudong Kong, Meltem Isik, Jin Zhang, Hee Woong Lim, John C. Yoon

Research output: Contribution to journalArticlepeer-review

Abstract

Manipulation of energy-dissipating adipocytes has the potential to produce metabolic benefits. To this end, it is valuable to understand the mechanisms controlling the generation and function of thermogenic fat. Here, we identify Letm1 domain containing 1 (Letmd1) as a regulator of brown fat formation and function. The expression of Letmd1 is induced in brown fat by cold exposure and by β-adrenergic activation. Letmd1-deficient mice exhibit severe cold intolerance concomitant with abnormal brown fat morphology, reduced thermogenic gene expression, and low mitochondrial content. The null mice exhibit impaired β3-adrenoreceptor-dependent thermogenesis and are prone to diet-induced obesity and defective glucose disposal. Letmd1 was previously described as a mitochondrial protein, and we find that it also localizes to the nucleus and interacts with the transcriptional coregulator and chromatin remodeler Brg1/Smarca4, thus providing a way to impact thermogenic gene expression. Our study uncovers a role for Letmd1 as a key regulatory component of adaptive thermogenesis.

Original languageEnglish (US)
Article number110104
JournalCell Reports
Volume37
Issue number11
DOIs
StatePublished - Dec 14 2021

Keywords

  • brown fat
  • Letmd1
  • thermogenesis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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