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TREM2 has a significant, gender-specific, effect on human obesity

Tzila Reich1, Orit Adato1, Naomi Schneid Kofman1

  • 1Faculty of Life Sciences, The Mina and Everard Goodman, Bar-Ilan University, 52900, Ramat Gan, Israel.

Scientific Reports
|January 10, 2023
PubMed

Insights

Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) is linked to human obesity. Computational analysis reveals TREM2 expression correlates with BMI in males and a specific TREM2 gene variant strongly impacts BMI in females.

Area of Science:

  • Immunology
  • Genetics
  • Metabolic Research

Background:

  • Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) is an immune cell membrane protein implicated in neurodegenerative diseases and cancer.
  • TREM2 is found on lipid-associated macrophages in adipose tissue, and TREM2 knockout mice exhibit metabolic symptoms.
  • Previous research suggests a role for TREM2 in metabolic processes, but its direct involvement in human obesity remains unclear.

Purpose of the Study:

  • To investigate the association between TREM2 and human obesity using computational analysis of public databases.
  • To explore potential gender-specific roles of TREM2 in obesity.
  • To identify genetic variants in TREM2 that may influence Body Mass Index (BMI).

Main Methods:

  • Analysis of TREM2 expression levels and BMI correlation in adipose tissue samples from the Genotype-Tissue Expression (GTEx) database.
  • Identification and association analysis of a coding single nucleotide polymorphism (SNP) in TREM2 with BMI in the UK Biobank cohort.
  • Comparison of the identified TREM2 SNP's association strength with previously known BMI-associated SNPs.

Main Results:

  • A significant correlation was found between TREM2 expression levels and BMI in male adipose tissue samples from GTEx.
  • A coding SNP in TREM2 (rs2234256, L211P) showed a strong association with BMI in the UK Biobank cohort, particularly in females.
  • This TREM2 SNP (rs2234256) demonstrated a more significant association with BMI than previously identified SNPs, with higher BMI in heterozygous and homozygous carriers.

Conclusions:

  • TREM2 plays a significant, gender-specific role in human obesity.
  • The findings suggest a novel mechanism linking TREM2 to obesity, particularly in females.
  • Further research is warranted to elucidate the precise molecular mechanisms underlying TREM2's influence on obesity.

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