Nutrition and GLP-1-Based Therapies in Obesity: Targeting Lipotoxicity and Metabolic Dysfunction

Metabolic disease arises from disturbances in energy balance, lipid metabolism, and glucose regulation, contributing to obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease. Lipotoxicity—the accumulation of excess lipid species in non-adipose tissues—links metabolic overload to adipose tissue dysfunction, chronic inflammation, insulin resistance, mitochondrial impairment, and progressive organ injury. Although substantial progress has been made in understanding these processes, important questions remain regarding how lipotoxicity develops, how it can be reversed, and why individuals respond differently to nutritional and pharmacological interventions.Nutritional intervention and GLP-1-based pharmacology have become central strategies for managing metabolic disease and reducing excessive lipid accumulation. Dietary composition, energy restriction, protein intake, meal timing, and dietary quality influence substrate utilization, hepatic lipid storage, insulin sensitivity, and body composition. In parallel, GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists have demonstrated substantial benefits for weight reduction, glycemic control, and liver outcomes. However, the mechanisms underlying these benefits, the interaction between dietary and pharmacological approaches, the preservation of skeletal muscle, the management of treatment-related adverse effects, and the durability of weight loss remain incompletely understood.This Research Topic aims to integrate mechanistic, translational, and clinical evidence on the roles of nutrition and GLP-1 pharmacology in the prevention and treatment of metabolic disease. It will address how these interventions regulate lipid and glucose metabolism, improve metabolic function, preserve healthy body composition, and contribute to the reversal of lipotoxicity. To gather further insights into the nutritional and pharmacological management of obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease, we welcome articles addressing, but not limited to, the following themes:- Cellular and molecular mechanisms of lipotoxicity, including ectopic lipid deposition, adipose tissue dysfunction, mitochondrial impairment, endoplasmic reticulum stress, oxidative stress, inflammation, and insulin resistance.- Nutritional regulation of lipid and glucose metabolism, including dietary composition, energy restriction, intermittent fasting, meal timing, dietary quality, and specific nutrients or bioactive compounds.- Evidence-based dietary patterns for obesity and metabolic disease management, including Mediterranean, low-carbohydrate, high-protein, plant-based, and other nutritionally appropriate approaches. -Nutritional strategies for metabolic dysfunction-associated steatotic liver disease (MASLD), including effects on hepatic lipid accumulation, liver inflammation, fibrosis risk, insulin sensitivity, and metabolic function. -Medical nutrition therapy and dietetic care during obesity pharmacotherapy, including nut-ritional assessment, individualized dietary counselling, shared decision-making, and multidisciplinary management. -Nutritional implications of GLP-1 receptor agonists, dual GIP/GLP-1 receptor agonists, and emerging incretin-based therapies, including effects on appetite, food intake, eating behaviour, diet quality, nutritional adequacy, and metabolic health.-Interactions between nutrition and GLP-1-based pharmacotherapy, including dietary approaches to optimize treatment response, improve gastrointestinal tolerance, support adherence, and promote long-term metabolic outcomes. -Skeletal muscle preservation and body composition during weight loss, including sarcopenia risk, lean-mass changes, protein intake, resistance exercise, physical function, and strategies to preserve metabolically healthy tissue. -Nutritional adequacy and management of treatment-related adverse effects during pharmacologically induced weight loss, including protein and micronutrient intake, prevention of nutritional deficiencies, and dietary management of gastrointestinal symptoms. -Treatment durability and metabolic adaptation, including weight-loss plateaus, appetite and energy-expenditure changes, weight regain after treatment discontinuation, and nutritional strategies for long-term maintenance. -Individual variability and clinical outcomes of integrated nutrition and pharmacotherapy approaches, including the influence of metabolic phenotype, baseline body composition, genetics, comorbidities, nutritional status, dietary adherence, and real-world treatment response. By bringing together research from metabolism, nutrition, endocrinology, pharmacology, and hepatology, this Research Topic will advance the understanding and clinical application of nutrition and GLP-1-based therapies for metabolic disease and lipotoxicity reversal. Topic editors: Yiping Cheng, Chao Xu, Junming Han, Li Wang Source: https://www.frontiersin.org/research-topics/85421/nutrition-and-glp-1-based-therapies-in-obesity-targeting-lipotoxicity-and-metabolic-dysfunction