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

Abstract

Triggering receptor expressed on myeloid 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/enhancer-binding protein α, was markedly increased in HFD-fed TG mice. Additionally, HFD-fed TG mice exhibited decreased Wnt10b expression and increased GSK-3β (glycogen synthase kinase-3β)-mediated β-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/β-catenin signaling pathway.

• Authors: 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-Hoon Kim, Hyung-Sik Kang
• Journal: Diabetes (Diabetes) Vol. 64 Issue 1 Pg. 117-27 (Jan 2015) ISSN: 1939-327X [Electronic] United States
• PMID: 25114293 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Chemical References

• Membrane Glycoproteins
• Receptors, Immunologic
• Trem2 protein, mouse

Topics

• 3T3-L1 Cells
• Adipocytes (cytology, immunology, metabolism)
• Adipogenesis (physiology)
• Animals
• Calorimetry, Indirect
• Cell Differentiation (physiology)
• Diet, High-Fat
• Energy Metabolism (physiology)
• Fibroblasts (cytology, immunology, metabolism)
• Insulin Resistance (physiology)
• Male
• Membrane Glycoproteins (genetics, immunology, metabolism)
• Mice
• Mice, Transgenic
• Myeloid Cells (cytology, immunology, metabolism)
• Obesity (genetics, immunology, metabolism)
• Primary Cell Culture
• Receptors, Immunologic (genetics, immunology, metabolism)
• Signal Transduction (physiology)
• Wnt Signaling Pathway (physiology)