New Therapeutic Approaches for the Treatment of Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Increased Cardiovascular Risk.

Metabolic dysfunction-associated steatotic liver disease (MASLD) was previously known as nonalcoholic fatty liver disease (NAFLD). The main characteristic of the disease is the process of long-term liver inflammation, which leads to hepatocyte damage followed by liver fibrosis and eventually cirrhosis. Additionally, these patients are at a greater risk for developing cardiovascular diseases (CVD). They have several pathophysiological mechanisms in common, primarily lipid metabolism disorders and lipotoxicity. Lipotoxicity is a factor that leads to the occurrence of heart disease and the occurrence and progression of atherosclerosis. Atherosclerosis, as a multifactorial disease, is one of the predominant risk factors for the development of ischemic heart disease. Therefore, CVD are one of the most significant carriers of mortality in patients with metabolic syndrome. So far, no pharmacotherapy has been established for the treatment of MASLD, but patients are advised to reduce their body weight and change their lifestyle. In recent years, several trials of different drugs, whose basic therapeutic indications include other diseases, have been conducted. Because it has been concluded that they can have beneficial effects in the treatment of these conditions as well, in this paper, the most significant results of these studies will be presented.

Therapeutic Potential of Palmitoylethanolamide in Gastrointestinal Disorders.

Palmitoylethanolamide (PEA) is an endocannabinoid-like bioactive lipid mediator belonging to the family of N-acylethanolamines, most abundantly found in peanuts and egg yolk. When the gastrointestinal (GI) effects of PEA are discussed, it must be pointed out that it affects intestinal motility but also modulates gut microbiota. This is due to anti-inflammatory, antioxidant, analgesic, antimicrobial, and immunomodulatory features. Additionally, PEA has shown beneficial effects in several GI diseases, particularly irritable bowel syndrome and inflammatory bowel diseases, as various studies have shown, and it is important to emphasize its relative lack of toxicity, even at high dosages. Unfortunately, there is not enough endogenous PEA to treat disturbed gut homeostasis, even though it is produced in the GI tract in response to inflammatory stimuli, so exogenous intake is mandatory to achieve homeostasis. Intake of PEA could be through animal and/or vegetable food, but bearing in mind that a high dosage is needed to achieve a therapeutic effect, it must be compensated through dietary supplements. There are still open questions pending to be answered, so further studies investigating PEA's effects and mechanisms of action, especially in humans, are crucial to implementing PEA in everyday clinical practice.