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Updated: Jun 12, 2025
Techniques of Sleeve Gastrectomy and Modified Roux-en-Y Gastric Bypass in Mice
Published on: March 20, 2017
TREM2 macrophages mediate the beneficial effects of bariatric surgery against MASH
Gavin Fredrickson1, Kira Florczak1, Fanta Barrow1
1Department of Integrative Biology & Physiology, University of Minnesota, Minneapolis, Minnesota, USA.
Background And Aims:
For patients with obesity and metabolic syndrome, bariatric procedures such as vertical sleeve gastrectomy (VSG) have a clear benefit in ameliorating metabolic dysfunction-associated steatohepatitis (MASH). While the effects of bariatric surgeries have been mainly attributed to nutrient restriction and malabsorption, whether immuno-modulatory mechanisms are involved remains unclear.
Approach And Result:
Using murine models, we report that VSG ameliorates MASH progression in a weight loss-independent manner. Single-cell RNA sequencing revealed that hepatic lipid-associated macrophages (LAMs) expressing the triggering receptor expressed on myeloid cells 2 (TREM2) repress inflammation and increase their lysosomal activity in response to VSG. Remarkably, TREM2 deficiency in mice ablates the reparative effects of VSG, suggesting that TREM2 is required for MASH resolution. Mechanistically, TREM2 prevents the inflammatory activation of macrophages and is required for their efferocytic function.
Conclusions:
Overall, our findings indicate that bariatric surgery improves MASH through a reparative process driven by TREM2+ macrophages, providing insights into the mechanisms of disease reversal that may result in new therapies and improved surgical interventions.
