Tong Yue, Xu Sai, Huang Lili, Chen Chen
Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia.
Drug Discov Today. 2022 Mar;27(3):822-830. doi: 10.1016/j.drudis.2021.11.001. Epub 2021 Nov 9.
The prevalence of obesity is a major cause of many chronic metabolic disorders, including type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and cancer. Insulin resistance is often associated with metabolic unhealthy obesity (MUO). Therapeutic approaches aiming to improve insulin sensitivity are believed to be central for the prevention and treatment of MUO. However, current antiobesity drugs are reported as multitargeted and their insulin-sensitizing effects remain unclear. In this review, we discuss current understanding of the mechanisms of insulin resistance from the aspects of endocrine disturbance, inflammation, oxidative, and endoplasmic reticulum stress (ERS). We then summarize the antiobesity drugs, focusing on their effects on insulin sensitivity. Finally, we discuss strategies for obesity treatment.
肥胖的流行是许多慢性代谢紊乱的主要原因，包括2型糖尿病（T2DM）、心血管疾病（CVD）和癌症。胰岛素抵抗通常与代谢不健康的肥胖（MUO）相关。旨在提高胰岛素敏感性的治疗方法被认为是预防和治疗MUO的核心。然而，据报道，目前的抗肥胖药物具有多靶点作用，其胰岛素增敏作用仍不明确。在这篇综述中，我们从内分泌紊乱、炎症、氧化和内质网应激（ERS）等方面讨论了对胰岛素抵抗机制的当前认识。然后，我们总结了抗肥胖药物，重点关注它们对胰岛素敏感性的影响。最后，我们讨论了肥胖治疗的策略。
