Link Between Endoplasmic Reticulum Stress and Lipid Metabolism in Metabolic and Neurodegenerative Diseases

Satisfactory Essays
Metabolic diseases and neurodegenerative diseases (ND) are the hallmarks of modern health issues, affecting millions of people worldwide. Even though these diseases have different phenotypic manifestations and symptoms, they share many pathophysiological characteristics such as chronic endoplasmic reticulum (ER) stress and the impairment of ER stress responses such as the unfolded protein response (UPR) that cannot re-establish homeostasis. In other studies, the disturbance in lipid metabolism in these diseases was also proven, noting that the majority of lipid metabolism in cells happens in the ER. In this review, we will discuss the relationship between ER stress and lipid metabolism that has been proposed in metabolic diseases, and the potential link between ER stress and lipid metabolism in ND diseases that remains to be unveiled. Proving the existence of a link between ER stress and lipid metabolism might be of great interest for the development of drugs that target not only single pathways in ND like current drugs do, but aim to target the connection between the different pathways responsible for the development of the disorders.
Endoplasmic reticulum functions
In eukaryotic cells, endoplasmic reticulum (ER) is an organelle responsible for many vital functions such as the production of secretory proteins, their folding and transport to the Golgi complex [1]*. The synthesis of sterol and phospholipids (principal components of lipids in biological membranes) also takes place in the ER:
Hence, the crucial role of ER in lipid metabolism and composition in membranes. ER maintains lipid homeostasis, which is important for normal functions of cells ([2] and references cited therein)**.
Endoplasmic reticulum stress and

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... metabolic diseases commonly found in obese mice [17].
Therefore, we can notice that lipids in their different physical and chemical forms have distinct and conflicting roles in ER stress in obesity. Chronic exposure to saturated FA induces ER stress. However,
MUFA and PUFA protect cells from ER stress.
3- The metabolic roundabout
In this review, the relationship between endoplasmic reticulum stress and lipid metabolism deregulation, and their roles in the pathogenesis of obesity have been covered. However, it is very interesting to note that all of the individual molecular pathways involved in the metabolic dysfunction in metabolic diseases (i.e. inflammation, glucose metabolism, lipid metabolism, amino acid metabolism, calcium balance, hormonal deregulation, mitochondrial dysfunction, ER stress, etc.) that were not covered in this review interact with each other.
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