To test whether enhancing the capability of adipose tissue to store lipids using antioxidant supplementation may prevent the lipotoxic effects and improve the metabolic profile of long‐term obesity.

C57BL/6J mice were randomized into three experimental groups for 28 weeks: control group (n = 10) fed chow diet (10% kcal from fat), obese group (O, n = 12) fed high‐fat (HF) diet (45% kcal from fat), and obese group fed HF diet and supplemented twice a week with 150 mg of α‐tocopherol (vitamin E) by oral gavage (OE, n = 12).

HF diet resulted in an obese phenotype with a marked insulin resistance, hypertriglyceridemia, and hepatic steatosis in O mice. Histological analysis of obese visceral adipose tissue (VAT) revealed smaller adipocytes surrounded by a fibrotic extracellular matrix and an increased macrophage infiltration, with the consequent release of proinflammatory cytokines. Vitamin E supplementation decreased oxidative stress and reduced collagen deposition in the VAT of OE mice, allowing a further expansion of the adipocytes and increasing the storage capability. As a result, circulating cytokines were reduced and hepatic steasosis, hypertriglyceridemia, and insulin sensitivity were improved.

Our results suggest that oxidative stress is implicated in extracellular matrix remodeling and may play an important role in metabolic regulation.