Exercise emerges as key regulator of lipid droplets across health conditions

A comprehensive narrative review published in Translational Exercise Biomedicine, (ISSN: 2942-6812), an official partner journal of International Federation of Sports Medicine (FIMS), sheds new light on the critical role of lipid droplets in human health and disease, and how exercise serves as a powerful modulator of their dynamics. The article, entitled “The impact of exercise on the role of lipid droplets in maintaining health: a narrative review” synthesizes current evidence on how these once-underestimated organelles contribute to various pathologies and how physical activity can counteract their detrimental effects.

Lipid droplets, long considered inert fat storage units, are now recognized as dynamic, multifunctional organelles involved in cellular signaling, immune response, and energy metabolism. This narrative review, led by Liangming Li’s team from Guangzhou Sport University and Guohua Zheng from Shanghai University of Sport, details how excessive or misplaced accumulation of lipid droplets is linked to a range of conditions, including metabolic dysfunction-associated fatty liver disease, viral infections, such as Hepatitis C, pancreatic cancer, kidney disease, and neurodegenerative disorders such as Alzheimer's and Parkinson's disease, etc. To compile this state-of-the-art narrative, the authors conducted an extensive literature search across PubMed, Google Scholar, and Web of Science, screening over 200,000 records published from 1894 to January 2025. The final analysis incorporated 152 articles, comprising 106 empirical studies and 46 reviews, selected through a rigorous, multi-stage process by independent investigators to minimize bias. Dr. Chunlu Fang from Guangzhou Sport University, the first author, remarked: “Our review underscores that lipid droplets are not just passive storage units, they are active signaling hubs. Understanding how exercise regulates them opens new avenues for preventing and treating metabolic and inflammatory diseases.”

A key focus of the article is the tissue-specific nature of lipid droplets. Their size, distribution, and function vary significantly across organs from large droplets in adipose tissue to smaller, rapidly turning over droplets in the heart and skeletal muscle. This heterogeneity underlies their diverse roles across health and different conditions.

The authors highlight that exercise induces beneficial effects across multiple tissues by promoting lipid droplet degradation through critical pathways like lipolysis and lipophagy. For instance, aerobic exercise was shown to activate the AMPK signaling pathway, down-regulate the lipid droplet-associated protein PLIN2, and enhance lysosomal activity, thereby reducing harmful lipid accumulation in the liver. In skeletal muscle, exercise remodels lipid droplets distribution by shifting from fewer, larger droplets linked to insulin resistance to numerous smaller droplets associated with improved metabolic health, which is considered as a phenomenon known as the “athlete’s paradox”.

This narrative review also explores how exercise mitigates lipid droplet-associated risks in other organs:

In the kidney, training improves lipid metabolism and glomerular filtration rate. In the lungs, it reduces inflammation and lipid droplet-driven pathology. In the skeletal muscle, beyond the athlete's paradox, exercise training also reduces harmful lipid intermediates and inflammation, protecting against age-related sarcopenia and muscular dystrophies. In the brain, physical activity supports cognitive function and may slow neurodegeneration by influencing lipid droplet turnover. Overall, these findings underscore the potential of exercise as a non-pharmacological strategy to combat diseases driven by lipid dysregulation.

Prof. Liangming Li from Guangzhou Sport University and Prof. Guohua Zheng from Shanghai University of Sport, two corresponding authors of this article, added: “This synthesis underscores that exercise is a potent, multi-target therapy. By regulating lipid droplet dynamics across tissues, it simultaneously addresses inflammation, metabolism, and immune function, offering a holistic approach to disease prevention.”

The authors conclude that while significant progress has been made, future research should focus on establishing lipid droplets as central signaling nodes and elucidating the precise effects of different exercise modalities, such as aerobic vs. resistance exercise, on the biology of lipid droplets in various diseases. This deeper understanding is expected to refine exercise prescriptions, turning physical activity into an even more precise and powerful tool for maintaining metabolic health and combating chronic diseases on a global scale.