Drug Design, Development and Therapy (Jul 2024)
Impact of Lipids on Insulin Resistance: Insights from Human and Animal Studies
Abstract
Rani Yulifah Elkanawati,1,* Sri Adi Sumiwi,2 Jutti Levita2,* 1Master Program in Pharmacy, Faculty of Pharmacy, Padjadjaran University, Jawa Barat, West Java, 45363, Indonesia; 2Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 45363, Indonesia*These authors contributed equally to this workCorrespondence: Jutti Levita, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 46363, Indonesia, Tel +6222-84288888 Ext 3510, Email [email protected]: Insulin resistance (IR) is a complex pathological condition central to metabolic diseases such as type 2 diabetes mellitus (T2DM), cardiovascular disease, non-alcoholic fatty liver disease, and polycystic ovary syndrome (PCOS). This review evaluates the impact of lipids on insulin resistance (IR) by analyzing findings from human and animal studies. The articles were searched on the PubMed database using two keywords: (1) “Role of Lipids AND Insulin Resistance AND Humans” and (2) “Role of Lipids AND Insulin Resistance AND Animal Models”. Studies in humans revealed that elevated levels of free fatty acids (FFAs) and triglycerides (TGs) are closely associated with reduced insulin sensitivity, and interventions like metformin and omega-3 fatty acids show potential benefits. In animal models, high-fat diets disrupt insulin signaling and increase inflammation, with lipid mediators such as diacylglycerol (DAG) and ceramides playing significant roles. DAG activates protein kinase C, which eventually impairs insulin signaling, while ceramides inhibit Akt/PKB, further contributing to IR. Understanding these mechanisms is crucial for developing effective prevention and treatment strategies for IR-related diseases.Keywords: high-fat diet, insulin resistance, lipid profile, type 2 diabetes mellitus
