Beneficial Metabolic Effects of TREM2 in Obesity Are Uncoupled From Its Expression on Macrophages. Academic Article uri icon

Overview

abstract

  • Obesity-induced white adipose tissue (WAT) hypertrophy is associated with elevated adipose tissue macrophage (ATM) content. Overexpression of the triggering receptor expressed on myeloid cells 2 (TREM2) reportedly increases adiposity, worsening health. Paradoxically, using insulin resistance, elevated fat mass, and hypercholesterolemia as hallmarks of unhealthy obesity, a recent report demonstrated that ATM-expressed TREM2 promoted health. Here, we identified that in mice, TREM2 deficiency aggravated diet-induced insulin resistance and hepatic steatosis independently of fat and cholesterol levels. Metabolomics linked TREM2 deficiency with elevated obesity-instigated serum ceramides that correlated with impaired insulin sensitivity. Remarkably, while inhibiting ceramide synthesis exerted no influences on TREM2-dependent ATM remodeling, inflammation, or lipid load, it restored insulin tolerance, reversing adipose hypertrophy and secondary hepatic steatosis of TREM2-deficient animals. Bone marrow transplantation experiments revealed unremarkable influences of immune cell-expressed TREM2 on health, instead demonstrating that WAT-intrinsic mechanisms impinging on sphingolipid metabolism dominate in the systemic protective effects of TREM2 on metabolic health.

publication date

  • February 24, 2021

Research

keywords

  • Adipose Tissue
  • Macrophages
  • Membrane Glycoproteins
  • Obesity
  • Receptors, Immunologic

Identity

PubMed Central ID

  • PMC8576425

Scopus Document Identifier

  • 85107286475

Digital Object Identifier (DOI)

  • 10.2337/db20-0572

PubMed ID

  • 33627323

Additional Document Info

volume

  • 70

issue

  • 9