Lipotoxicity: Effects of Dietary Saturated and Transfatty Acids

Abstract

The ingestion of excessive amounts of saturated fatty acids (SFAs) and transfatty acids (TFAs) is considered to be a risk factor for cardiovascular diseases, insulin resistance, dyslipidemia, and obesity. The focus of this paper was to elucidate the influence of dietary SFA and TFA intake on the promotion of lipotoxicity to the liver and cardiovascular, endothelial, and gut microbiota systems, as well as on insulin resistance and endoplasmic reticulum stress. The saturated and transfatty acids favor a proinflammatory state leading to insulin resistance. These fatty acids can be involved in several inflammatory pathways, contributing to disease progression in chronic inflammation, autoimmunity, allergy, cancer, atherosclerosis, hypertension, and heart hypertrophy as well as other metabolic and degenerative diseases. As a consequence, lipotoxicity may occur in several target organs by direct effects, represented by inflammation pathways, and through indirect effects, including an important alteration in the gut microbiota associated with endotoxemia. Interactions between these pathways may perpetuate a feedback process that exacerbates an inflammatory state. The importance of lifestyle modification, including an improved diet, is recommended as a strategy for treatment of these diseases.

Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation

“…Thus, reticulum stress disturbs hepatic lipid metabolism by deregulation of lipogenic genes, promotes insulin resistance, and activates several proinflammatory pathways as NF-B [73,74]. It has been described that the inflammatory response mediates the effect of dysbiosis and endotoxemia in ER stress development [75].…”

Eicosapentaenoic Acid Prevents Saturated Fatty Acid-Induced Vascular Endothelial Dysfunction: Involvement of Long-Chain Acyl-CoA Synthetase

“…It is known that the inflammatory response caused by these mediators induces vascular endothelial dysfunction and macrophage activation 9) , leading to the development and progression of atherosclerosis. In particular, an excess of saturated fatty acids is considered a risk factor for cardiovascular disease and has been reported to trigger inflammatory signals in various tissues and promote lipotoxicity 10) . In order to elucidate the mechanism of the anti-atherogenic effect of EPA, we studied lipotoxicity in vascular cells and showed that palmitic acid (PA), a major saturated fatty acid in plasma, stimulates inflammatory cytokine production in macrophages as well as osteoblastic differentiation of vascular smooth muscle cells, and that this action could be mediated by long-chain acyl-CoA synthetase (ACSL), an enzyme that converts free fatty acids into acyl-CoA derivatives 11,12) .…”

Diet containing partially hydrogenated vegetable fat enhances the carrageenan induced paw inflammation but not oxidative stress markers in liver of rats

“…The prolonged exposure to oxidative stress has been implicated in the development or acceleration of several diseases such as cardiovascular disease and autoimmune diseases (Estadella et al 2013).…”