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 g 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.

RETRACTED ARTICLE: TREM-1 associated macrophage polarization plays a significant role in inducing insulin resistance in obese population

“…Similarly, obese non-diabetics had a lower number of patients with down regulation of M2 markers (CD206 and CD163) in liver biopsy samples compared to non-obese subjects. The expression of TREM-2 and M2 markers in rest of the obese subjects indicates the compensatory mechanism to counter the ongoing inflammation, thereby controlling the insulin sensitivity and IR [44]. Our study results showed a negative association between increased TREM-1 and M2 markers (CD206 and CD163) in the liver biopsy tissues of the obese diabetic group.…”

TREM2-Ligand Interactions in Health and Disease

“…Other evidence suggested TREM2 and APOE could have overlapping areas of function. TREM2 has been linked to lipid metabolism: Trem2 transgenic mice gain more weight on a high fat diet [136], and expression analysis connected Trem2 to lipid metabolic pathways [29, 65]. Furthermore, APOE interacts with Aβ, lipids, and heparan sulfates [137], and is important for microglial functions including phagocytosis, inflammation, and cell health [138, 139].…”

Immunometabolism features of metabolic deregulation and cancer

“…Interesting evidence in this regard is presented recently by Bekkering et al who reported that metabolic signals can induce trained immunity. Series of experiments showed that cholesterol synthesis pathway is essential for training of myeloid cells, which in turn are implicated in adiposeness and obesity . Furthermore, innate lymphoid cells (ILC) that are a group of tissue‐resident immune cells have been revealed to exert their vital functions through hosts dietary components and metabolites, which simultaneously affects host metabolism .…”