Endoplasmic Reticulum Stress and Metabolic Syndrome: Mechanisms and Therapeutic Potential

Abstract

Abstract: The nomenclature "metabolic syndrome" refers to a cluster of disorders including obesity, dyslipidemia, hypertension, and insulin resistance. It is a primary risk factor for cardiovascular and neurological diseases accompanied by dysregulated adipokines (cytokines and chemokines) and leptin, a peptide hormone secreted by white adipose tissue. These changes modulate immune and inflammatory responses, prompting the reset of the hypothalamic “body weight/appetite/satiety set point”. The precise tie between metabolic syndrome and neurological disorders such as stroke, depression and Alzheimer's disease remains largely elusive. A number of cellular and molecular mechanisms have been put forward for the metabolic syndrome-associated cardiovascular and neurological anomalies including oxidative stress, alteration in glucose and lipid metabolism, abnormal insulin and leptin signaling, apoptosis, and autophagy. More recent evidence depicted that endoplasmic reticulum (ER) stress, also known as unfolded protein response (UPR), gets activated in the context of metabolic syndrome. Hypothalamic ER stress leads to inflammation and resistance to leptin/insulin signaling. Hepatic ER stress promotes the onset and development of insulin resistance while ER stress in adipose tissues facilitates inflammation to cause secretion of adipokines. To the contrary, inflammation aggravates ER stress. ER stress activates autophagy while autophagy induction may, in turn, enhance ER stress. These interplays between ER stress and cell injurious machinery compromise insulin signaling, thereby contributing to the onset and development of metabolic syndrome. This synthetic min-review of recent literature not only describes the involvement of cardiovascular and neurological systems in the pathogenesis of metabolic syndrome, but also dissects the role of ER stress as well as its interplay with autophagy and inflammation in cardiovascular and neurological disorders in metabolic syndrome.

Key words: metabolic syndrome, obesity, cardiovascular, neurological, risk factors

CLC Number:

R589
R741

XIA Zhi, ZHANG Ying-mei, REN Jun. Endoplasmic Reticulum Stress and Metabolic Syndrome: Mechanisms and Therapeutic Potential[J]. ACTA NEUROPHARMACOLOGICA, 2012, 2(1): 33-44.

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