CREG1 improves diet-induced obesity via uncoupling protein 1-dependent manner in mice.

Genes Cells

Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai, Japan.

Published: March 2022

AI Article Synopsis

  • Thermogenic brown and beige fat cells play a crucial role in regulating energy metabolism and protecting against obesity and related diseases by expressing uncoupling protein 1 (UCP1).* -
  • The study explored how administering Cellular repressor of E1A-stimulated genes 1 (CREG1) affects UCP1 and diet-induced obesity (DIO) in mice at a comfortable temperature of 30°C, leading to increased UCP1 levels and reduced body fat.* -
  • Results showed that CREG1 treatment boosted energy metabolism and fat browning in mice, but this effect was absent in UCP1-knockout mice, highlighting the essential role of UCP1 in combating obesity through CREG

Article Abstract

Thermogenic brown and beige adipocytes express uncoupling protein 1 (UCP1) and stimulate energy metabolism, protecting against obesity and metabolic diseases such as type 2 diabetes and hyperlipidemia. Cellular repressor of E1A-stimulated genes 1 (CREG1) can stimulate thermogenic fat formation, induce UCP1, and reduce diet-induced obesity (DIO) in mice at normal room temperature. In this study, we investigated the effect of CREG1 administration and the importance of UCP1 in DIO inhibition under thermoneutral conditions at 30°C, which attenuate thermogenic fat formation. Interestingly, subcutaneous administration of recombinant CREG1 protein via an osmotic pump in C57BL/6J mice for four weeks increased UCP1 expression in interscapular brown adipose tissue (IBAT), inhibited visceral white fat hypertrophy with partial browning, and reduced DIO compared to that in PBS-treated mice. The mRNA expression of energy metabolism-related genes was significantly increased in the IBAT of CREG1-treated mice compared to that in PBS-treated mice. In contrast, adipocyte-specific overexpression of CREG1 failed to improve DIO in UCP1-knockout mice at thermoneutrality. Our results indicate the therapeutic potential of CREG1 administration for obesity under thermogenic fat-attenuating conditions and highlight the indispensable role of UCP1 in the DIO-inhibitory effect of CREG1.

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Source
http://dx.doi.org/10.1111/gtc.12920DOI Listing

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