Pharmacologic Inhibition of Interleukin-6 by Tocilizumab as a Potential Therapy for Prediabetes Redirecting Fat Distribution from Visceral to Subcutaneous Adiposity and Metabolic Restoration

Interleukin-6 (IL-6), a pleiotropic cytokine pivotal to adipose homeostasis, has emerged as a key mediator in prediabetes pathogenesis. Within senescent visceral adipose tissue (VAT) adipocytes, hypoxia-inducible factor-1α (HIF-1α)-driven IL-6 amplification triggers Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling, inducing suppressor of cytokine signaling 3 (SOCS3) feedback and perpetuating lipolytic inhibition, ectopic lipid deposition, and insulin resistance. This work proposes a therapeutic redirection of adipose fate via pharmacologic IL-6 blockade using tocilizumab, hypothesized to shift lipid storage from VAT to subcutaneous adipose tissue (SCAT). Mechanistically, IL-6 inhibition restores hormone-sensitive lipase (HSL) phosphorylation, peroxisome proliferator-activated receptor-γ (PPAR-γ) activation, and perilipin-1 integrity, fostering benign lipid buffering and improved insulin sensitivity. Clinical data indicate 12–20% VAT regression, 8–10% SCAT expansion, 70% CRP reduction, and 25% HOMA-IR improvement with tocilizumab, paralleling outcomes observed with structured exercise regimens. IL-6 levels ≥3 pg/mL demonstrate 75% diagnostic sensitivity for VAT-dominant prediabetes, suggesting biomarker-guided therapeutic stratification. Collectively, IL-6 antagonism delineates a cytokine-centric therapeutic axis bridging adipose inflammation to insulin resistance reversal, establishing a metabolic rationale for targeted prediabetes immunotherapy.