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Pitt Study Identifies SerpinB2 as Key to Protective Fat Macrophages, Pointing to a New Diabetes Treatment Path

A preclinical Nature Communications report maps a mechanism that preserves resident immune cells in visceral fat, guiding plans for small‑molecule testing.

Overview

  • University of Pittsburgh researchers report that SerpinB2 supports survival of tissue‑resident macrophages in visceral fat, which suppress inflammation linked to insulin resistance.
  • In obesity, SerpinB2 levels fall and resident macrophages decline, increasing adipose inflammation and worsening insulin response in mouse models and human fat samples.
  • Selective depletion of these resident macrophages aggravated glucose intolerance in obese mice, while protecting them improved metabolic outcomes.
  • Antioxidant supplementation in insulin‑resistant mice boosted resident macrophage levels and improved insulin sensitivity, reinforcing the proposed mechanism.
  • The team is pursuing a small molecule to raise SerpinB2 for human trials, framing the approach as a potential complement or alternative to GLP‑1 drugs pending clinical evidence.