Obesity-related hypoxia via miR-128 decreases insulin-receptor expression in human and mouse adipose tissue promoting systemic insulin resistance

miR-128 引起的肥胖相关缺氧会降低人类和小鼠脂肪组织中的胰岛素受体表达,从而促进全身胰岛素抵抗

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作者:Biagio Arcidiacono, Eusebio Chiefari, Anna Foryst-Ludwig, Giuseppe Currò, Giuseppe Navarra, Francesco S Brunetti, Maria Mirabelli, Domenica M Corigliano, Ulrich Kintscher, Domenico Britti, Vincenzo Mollace, Daniela P Foti, Ira D Goldfine, Antonio Brunetti

Background

Insulin resistance in visceral adipose tissue (VAT), skeletal muscle and liver is a prominent feature of most patients with obesity. How this association arises remains poorly understood. The

Methods

To clarify the role of INSR and insulin signaling in adipose tissue dysfunction in obesity, we first measured INSR expression in VAT samples from normal-weight subjects and patients with different degrees of obesity. We complemented these studies with experiments on high-fat diet (HFD)-induced obese mice, and in human and murine adipocyte cultures, in both normoxic and hypoxic conditions. Findings: An inverse correlation was observed between increasing body mass index and decreasing INSR expression in VAT of obese humans. Our

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