Unstressing the Reticulum: Nutritional Strategies for Modulating Endoplasmic Reticulum Stress in Obesity

Abstract The progression of obesity involves several molecular mechanisms that are closely associated with the pathophysiological response of the disease. Endoplasmic reticulum (ER) stress is one such factor. Lipotoxicity disrupts endoplasmic reticulum homeostasis in the context of obesity. Furthermore, it induces ER stress by activating several signaling pathways via inflammatory responses and oxidative stress. ER performs crucial functions in protein synthesis and lipid metabolism; thus, triggers such as lipotoxicity can promote the accumulation of misfolded proteins in the organelle. The accumulation of these proteins can lead to metabolic disorders and chronic inflammation, resulting in cell death. Thus, alternatives, such as flavonoids, amino acids, and polyphenols that are associated with antioxidant and anti‐inflammatory responses have been proposed to attenuate this response by modulating ER stress via the administration of nutrients and bioactive compounds. Decreasing inflammation and oxidative stress can reduce the expression of several ER stress markers and improve clinical outcomes through the management of obesity, including the control of body weight, visceral fat, and lipid accumulation. This review explores the metabolic changes resulting from ER stress and discusses the role of nutritional interventions in modulating the ER stress pathway in obesity.