Triggering receptor expressed on myeloid cells 2 (TREM2) promotes adipogenesis and diet-induced obesity

Min Park, Ja Woon Yi, Eun Mi Kim, Il Joo Yoon, Eun Hee Lee, Hwa Youn Lee, Kon Young Ji, Kwang Ho Lee, Ji Hun Jang, Seung Su Oh, Chul Ho Yun, Seung Hyung Kim, Ki Mo Lee, Mun Gyu Song, Dong-Hun Kim, Hyung Sik Kang

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19 Citations (Scopus)

Abstract

Triggering receptor expressed onmyeloid cells 2 (TREM2) is known to be involved in the anti-inflammatory response and osteoclast development. However, the role of TREM2 in adipogenesis or obesity has not yet been defined. The effect of TREM2 on adipogenesis and obesity was investigated in TREM2 transgenic (TG) mice on a high-fat diet (HFD). To block TREM2 signaling, a neutralizing fusion protein specific for TREM2 (TREM2- Ig) was used. TG mice were much more obese than wild-type mice after feeding with an HFD, independent of the quantity of food intake. These HFD-fed TG mice manifested adipocyte hypertrophy, glucose and insulin resistance, and hepatic steatosis. The expression of adipogenic regulator genes, such as peroxisome proliferator-Activated receptor γ and CCAAT/enhancerbinding protein a, was markedly increased in HFD-fed TG mice. Additionally, HFD-fed TG mice exhibited decreased Wnt10b expression and increased GSK-3b (glycogen synthase kinase-3b)-mediated b-catenin phosphorylation. In contrast, the blockade of TREM2 signaling using TREM2-Ig resulted in the inhibition of adipocyte differentiation in vitro and a reduction in body weight in vivo by downregulating the expression of adipogenic regulators. Our data demonstrate that TREM2 promotes adipogenesis and diet-induced obesity by upregulating adipogenic regulators in conjunction with inhibiting the Wnt10b/b-catenin signaling pathway.

Original languageEnglish
Pages (from-to)117-127
Number of pages11
JournalDiabetes
Volume64
Issue number1
DOIs
Publication statusPublished - 2015 Jan 1

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Park, M., Yi, J. W., Kim, E. M., Yoon, I. J., Lee, E. H., Lee, H. Y., Ji, K. Y., Lee, K. H., Jang, J. H., Oh, S. S., Yun, C. H., Kim, S. H., Lee, K. M., Song, M. G., Kim, D-H., & Kang, H. S. (2015). Triggering receptor expressed on myeloid cells 2 (TREM2) promotes adipogenesis and diet-induced obesity. Diabetes, 64(1), 117-127. https://doi.org/10.2337/db13-1869