هیدروکسی تیروئول باعث کاهش مقاومت به انسولین توسط مدولاسیون استرس تناسلی اندوپلاسمی و جلوگیری از استئاتوز کبدی در موش های چاقی ناشی از رژیم غذایی

Endoplasmic reticulum (ER) is a principal organelle responsible for energy and nutrient management. Its dysfunction has been viewed as the context of obesity and related glucolipid metabolic disorders. However, therapeutic approaches to improve ER adaptation and systemic energy balance in obesity are limited. Thus, we examined whether hydroxytyrosol (HT), an important polyphenolic compound found in virgin olive oil, could correct the metabolic impairments in diet-induced obesity (DIO) mice. Here, we found that HT gavage for 10 weeks significantly ameliorated glucose homeostasis, chronic inflammation and decreased hepatic steatosis in DIO mice. At the molecular level, ER stress indicators, inflammatory and insulin signaling markers demonstrated that high-fat diet (HFD)-induced ER stress and insulin resistance (IR) in insulin sensitive tissue were corrected by HT. In vitro studies confirmed that HT supplementation (100 μM) attenuated palmitate-evoked ER stress, thus rescued the downstream JNK/IRS pathway. As a result from suppression of ER stress in the liver, HT further decreased hepatic sterol regulatory element-binding protein-1 expression (SREBP1). Additionally, aberrant expression of genes involved in hepatic lipogenesis (SREBP1, ACC, FAS, SCD1) caused by HFD were restored by HT. These findings suggested HT ameliorated chronic inflammation and IR, decreased hepatic steatosis in obesity, by beneficial modulation of ER stress.