“Analysis of biochemical pathways involved into protective effects of bioactive compounds: focus on Omega-3 Polyunsaturated Fatty Acids”

Abstract

Dietary fat sources differently affect cellular metabolism, with different effects on metabolic disease risks. In the present PhD thesis, it was evaluated the effect of Omega-3 Polyunsaturated Fatty Acids (Omega-3 PUFAs), on the biochemical pathways involved in cellular metabolism, which can play an important role in metabolic diseases associated with obesity, such as hepatic steatosis and reproductive dysfunction, as well as in carcinogenesis processes and anti-cancer therapy. It is well known that, at the cellular level, metabolic pathways involved in stress and cell death are: 1) mitochondrial dysfunction associated with oxidative stress and alteration of mitochondrial dynamics behaviour, and 2) endoplasmic reticulum stress (ER stress). Mitochondria are highly dynamic organelles that continuously undergo fusion and fission processes, which are regulated by the protein mitofusin 2 (MFN2) and dynamin-related protein 1 (DRP1), respectively. Maintaining a correct balance between mitochondrial fusion and fission is necessary to maintain correct morphology, distribution and functionality of the mitochondria. In fact, an imbalance towards mitochondrial fission processes is associated with mitochondrial dysfunction, mitophagy and autophagy. Another mechanism involved in cellular metabolic dysfunction is ER stress, which activates the unfolded protein response pathway (UPR) and can trigger inflammatory processes and apoptosis.It is well known that Omega-3 PUFAs have anti-inflammatory effects, whereas little is known on the effect of Omega-3 PUFAs at the cellular level on the processes of mitochondrial dynamics behaviour

and ER stress. Protective mechanisms against mitochondrial dysfunction, oxidative stress and ER stress could be activated by Omega-3 PUFAs to counteract the obesity induced metabolic dysfunctions, as well as they could be at the basis of the adjuvant effect of Omega-3 PUFAs in therapy with anticancer drugs. [...] [edited by Author]