GREM2 is associated with human central obesity and inhibits visceral preadipocyte browning

LGR4: A New Receptor Member in Endocrine and Metabolic Diseases

“…To identify other potential LGR4 endogenous ligands, we examined the changes in the expression of Rspo1 - 4 , Rankl , Norrin , and Grem1/2 in brown fat, vWAT, and liver tissues of Lgr4 knockout mice and detected increased expression of Grem2 with corresponding changes in its plasma levels ( 191 ). Interestingly, GREM2 can bind directly to BMP4/7 and antagonize their roles in promoting adipose browning ( 191 ).…”

“…To identify other potential LGR4 endogenous ligands, we examined the changes in the expression of Rspo1 - 4 , Rankl , Norrin , and Grem1/2 in brown fat, vWAT, and liver tissues of Lgr4 knockout mice and detected increased expression of Grem2 with corresponding changes in its plasma levels ( 191 ). Interestingly, GREM2 can bind directly to BMP4/7 and antagonize their roles in promoting adipose browning ( 191 ). Considering that Norrin can bind directly to both BMP2/4 and LGR4, we speculate that GREM2 may also bind to LGR4 and play a role in suppressing the browning of visceral fat, possibly in a Wnt/β-catenin–independent way ( 191 ).…”

“…Interestingly, GREM2 can bind directly to BMP4/7 and antagonize their roles in promoting adipose browning ( 191 ). Considering that Norrin can bind directly to both BMP2/4 and LGR4, we speculate that GREM2 may also bind to LGR4 and play a role in suppressing the browning of visceral fat, possibly in a Wnt/β-catenin–independent way ( 191 ). This hypothesis certainly requires experimental validation.…”

Single-cell RNA sequencing in juvenile idiopathic arthritis

“… 85 Liu et al revealed that GREM2 inhibited the browning program of visceral preadipocytes by antagonizing the BMP4/7-SMAD1/5/8 signaling pathway. 86 These results implied that GREM1 and GREM2 could regulate the immune response and fibroblast differentiation through the BMP signaling pathway.…”

Gremlin 2 could explain the reduced capacity of browning of visceral adipose tissue

“…In a recent issue of EBioMedicine , Liu et al. 5 described increased levels of circulating Gremlin 2 (Grem2) in association to central obesity and visceral adiposity in three independent cohorts. This relationship was supported in murine experiments, in which Grem2 expression was significantly increased in epididymal (visceral) white adipose tissue (eWAT), and when this fat depot was surgical removed, plasma Grem2 levels were modestly decreased.…”