AUTHOR=Nakamura Michinari TITLE=Lipotoxicity as a therapeutic target in obesity and diabetic cardiomyopathy JOURNAL=Journal of Pharmacy & Pharmaceutical Sciences VOLUME=27 YEAR=2024 URL=https://www.frontierspartnerships.org/journals/journal-of-pharmacy-pharmaceutical-sciences/articles/10.3389/jpps.2024.12568 DOI=10.3389/jpps.2024.12568 ISSN=1482-1826 ABSTRACT=

Unhealthy sources of fats, ultra-processed foods with added sugars, and a sedentary lifestyle make humans more susceptible to developing overweight and obesity. While lipids constitute an integral component of the organism, excessive and abnormal lipid accumulation that exceeds the storage capacity of lipid droplets disrupts the intracellular composition of fatty acids and results in the release of deleterious lipid species, thereby giving rise to a pathological state termed lipotoxicity. This condition induces endoplasmic reticulum stress, mitochondrial dysfunction, inflammatory responses, and cell death. Recent advances in omics technologies and analytical methodologies and clinical research have provided novel insights into the mechanisms of lipotoxicity, including gut dysbiosis, epigenetic and epitranscriptomic modifications, dysfunction of lipid droplets, post-translational modifications, and altered membrane lipid composition. In this review, we discuss the recent knowledge on the mechanisms underlying the development of lipotoxicity and lipotoxic cardiometabolic disease in obesity, with a particular focus on lipotoxic and diabetic cardiomyopathy.