title: 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.affiliation: School of Biological Sciences and Technology, Chonnam National University, Buk-gu, Gwangju, Republic of Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Park
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, Buk-gu, Gwangju, Republic of Korea.
authors.forename: Ja-Woon
authors.initials: JW
authors.lastname: Yi
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, Buk-gu, Gwangju, Republic of Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Kim
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, Buk-gu, Gwangju, Republic of Korea.
authors.forename: Il-Joo
authors.initials: IJ
authors.lastname: Yoon
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, Buk-gu, Gwangju, Republic of Korea.
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Lee
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, Buk-gu, Gwangju, Republic of Korea.
authors.forename: Hwa-Youn
authors.initials: HY
authors.lastname: Lee
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, Buk-gu, Gwangju, Republic of Korea.
authors.forename: Kon-Young
authors.initials: KY
authors.lastname: Ji
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, Buk-gu, Gwangju, Republic of Korea.
authors.forename: Kwang-Ho
authors.initials: KH
authors.lastname: Lee
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, Buk-gu, Gwangju, Republic of Korea.
authors.forename: Ji-Hun
authors.initials: JH
authors.lastname: Jang
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, Buk-gu, Gwangju, Republic of Korea.
authors.forename: Seung-Su
authors.initials: SS
authors.lastname: Oh
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, Buk-gu, Gwangju, Republic of Korea.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Yun
authors.affiliation: Institute of Traditional Medicine and Bioscience, Daejeon University, Daejeon, Republic of Korea.
authors.forename: Seung-Hyung
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Traditional Korean Medicine Converging Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.
authors.forename: Ki-Mo
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Mun-Gyu
authors.initials: MG
authors.lastname: Song
authors.affiliation: Department of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Kim
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, Buk-gu, Gwangju, Republic of Korea kanghs@jnu.ac.kr.
authors.forename: Hyung-Sik
authors.initials: HS
authors.lastname: Kang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D002153:Calorimetry, Indirect; D002454:Cell Differentiation / Q000502:physiology; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D061251:Primary Cell Culture; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000502:physiology
chemical_list: D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C498716:Trem2 protein, mouse