Endoplasmic Reticulum Stress and Unfolded Protein Response in Metabolic Syndrome

The pathophysiologyHypertensionpathophysiology of Metabolic Syndrome (MetS) involves a complex interplay of factors, with endoplasmic reticulum (ER) stress and the unfolded protein responseRole of ER stress and UPR in the multifactorial metabolic syndromeunfolded protein response (UPR) emerging as significant contributors. This syndrome, characterized by a cluster of cardiovascular riskCardiovascular risk factors including obesity, hypertension, dyslipidemiaDyslipidemia, and insulin resistance, is closely linked to dysregulated ER stress responses. Elevated ER stress triggers the upregulation of key chaperonesChaperones and markers such as GRP78, GRP94, CHOP, Herp, XBP1, PERK, eIF2α, ATF4, and ATF6, exacerbating conditions like leptinLeptin resistanceEndoplasmic Reticulum Stressleptin resistance, insulin resistance, Type 2 diabetesDiabetes mellitus (T2DM), non-alcoholic fatty liver diseaseEndoplasmic Reticulum Stressnon-alcoholic fatty liver disease (NAFLD), hyperhomocysteinemiaHyperhomocysteinemia, alcoholic fatty liver disease (AFLD), andEndoplasmic Reticulum Stressatherosclerosis atherosclerosisAtherosclerosis. Recognizing the therapeutic potential, efforts have been made to identify ER stress inhibitors, which include anti-diabetic compounds like Metformin, Dapaglifozin, Sitagliptin, synthetic ER stress inhibitors like 4-PBA, and Salubrinal, as well as natural agents like TUDCA, proanthocyanidins, crocin, and various phenolic compounds. These inhibitors hold promise in mitigating exaggerated ER stress responses, offering potential avenues for managing metabolic syndrome and its associated complications. The book chapter thus aims to focus on the role of ER and uncover the link between ER, UPR and relevance of ER stress in the causal of MetS.