Endogenous Lipid Signals in Energy Homeostasis and Fibrosis

Endogenous bioactive lipids are complex signaling mediators actively involved in a plethora of pathophysiological processes, including energy homeostasis and fibrosis. Energy homeostasis is a stable internal state resulting from a dynamic balance between energy expenditure and storage. Dysregulated energy balance can contribute to fibrosis, exhibiting key metabolic effects on insulin sensitivity, glucose tolerance, lipid accumulation and metabolism, as well as on energy expenditure, ultimately leading to metabolic disorders. In this context, three major classes of endogenous lipid mediators derived from polyunsaturated fatty acids (PUFAs)—eicosanoids, specialized pro-resolving mediators, and endocannabinoids—represent a key signaling network involved in the regulation of energy metabolism. Hence, alterations in their metabolism and signaling are often associated with fibrosis and other related molecular changes. Here, we provide a comprehensive overview of the role of the above-mentioned lipid classes in energy homeostasis and fibrosis by reviewing the available literature spanning nearly four decades, with a primary focus on studies published over the past 20 years.