2. Academic Validation
  3. Sphingomyelin is involved in regulating UCP1-mediated nonshivering thermogenesis

Sphingomyelin is involved in regulating UCP1-mediated nonshivering thermogenesis

  • J Lipid Res. 2024 May 9;65(6):100559. doi: 10.1016/j.jlr.2024.100559.
Detian Hu 1,  Houyu Zhang 1,  Zhen Liu 2,  Carlos F Ibáñez 3,  Cai Tie 4,  Meng Xie 5
Affiliations

Affiliations

  • 1 Chinese Institute for Brain Research, Zhongguancun Life Science Park, Beijing, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
  • 2 Yuanpei College, Peking University, Beijing, China.
  • 3 Chinese Institute for Brain Research, Zhongguancun Life Science Park, Beijing, China; School of Life Sciences, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Beijing, China; PKU-IDG/McGovern Institute for Brain Research, Beijing, China; Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
  • 4 State Key Laboratory for Fine Exploration and Intelligent Development of Coal Resources, China University of Mining and Technology-Beijing, Beijing, China; School of Chemical and Environmental Engineering, China University of Mining and Technology-Beijing, Beijing, China.
  • 5 PKU-IDG/McGovern Institute for Brain Research, Beijing, China; School of Psychological and Cognitive Sciences, Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing, China; Department of Biosciences and Nutrition, Karolinska Institute, Flemingsberg, Sweden. Electronic address: meng.xie@pku.edu.cn.
PMID: 38729351 DOI: 10.1016/j.jlr.2024.100559
Abstract

Adipogenesis is one of the major mechanisms for adipose tissue expansion, during which spindle-shaped mesenchymal stem cells commit to the fate of adipocyte precursors and differentiate into round-shaped fat-laden adipocytes. Here, we investigated the lipidomic profile dynamics of ex vivo-differentiated brown and white adipocytes derived from the stromal vascular fractions of interscapular brown (iBAT) and inguinal white adipose tissues. We showed that sphingomyelin was specifically enriched in terminally differentiated brown adipocytes, but not white adipocytes. In line with this, freshly isolated adipocytes of iBAT showed higher sphingomyelin content than those of inguinal white adipose tissue. Upon cold exposure, sphingomyelin abundance in iBAT gradually decreased in parallel with reduced sphingomyelin synthase 1 protein levels. Cold-exposed Animals treated with an inhibitor of sphingomyelin hydrolases failed to maintain core body temperature and showed reduced oxygen consumption and iBAT UCP1 levels. Conversely, blockade of sphingomyelin synthetic Enzymes resulted in enhanced nonshivering thermogenesis, reflected by elevated body temperature and UCP1 levels. Taken together, our results uncovered a relation between sphingomyelin abundance and fine-tuning of UCP1-mediated nonshivering thermogenesis.

Keywords

UCP1; UPLC-HRMS; adipocyte; adipogenesis; adipose tissue; sphingolipid; sphingomyelin; thermogenesis.

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