Abstract
Obesity is a global health issue linked to the heightened risk of several chronic diseases. Rhus verniciflua (RV) is a traditional food supplement used for a range of pharmacological effects such as antitumor, antioxidant, α-glucosidase inhibitory effects, hepatitis, and arthritis. Despite the traditional medicinal values, scientific evidence for its application in obesity is inadequate and unclear. Thus, this investigation was designed to evaluate the anti-obesity effects of IBF-R, an RV extract, using a high-fat diet (HFD) model. The study has six groups: chow diet group; chow diet with 80 mg/kg IBF-R; HFD group; IBF-R group with 20, 40, and 80 mg/kg. IBF-R supplementation significantly regulated the weight gain than the HFD fed mice. Further, IBF-R supplementation lowered the expressions of adipogenic transcription factors such as SREBP-1c, C/EBPα, FAS, and PPAR-γ in white adipose tissue (WAT) of diet-induced obese mice. In addition, IBF-R supplementation reduced the lipogenic gene expression while enhancing genes was related to fatty acid oxidation. Obesity is linked to redox-based post-translational modifications (PTMs) of IRE1α such as S-nitrosylation, endoplasmic reticulum (ER) stress, and chronic metabolic inflammation. The administration of IBF-R inhibits these PTMs. Notably, IBF-R administration significantly enhanced the expression of AMPK and sirtuin 1 in WAT of HFD-fed mice. Together, these findings reveal the IRE1α S-nitrosylation-inflammation axis as a novel mechanism behind the positive implications of IBF-R on obesity. In addition, it lays a firm foundation for the development of Rhus verniciflua extract as a functional ingredient in the food and pharmaceutical industries.
Highlights
Obesity is abnormal fat accumulation in adipose tissues and characterized by body mass index (BMI) higher than 30 kg/m2 and is associated with multiple chronic diseases such as type 2 diabetes, cardiovascular disorders, and different types of cancers [1]
These findings show that S-nitrosylation targets IRE1α raising the potential changes in the functioning of IRE1α in obese adipose tissue
This study revealed the potential influence of IBF-R on obesity and extrapolated mechanisms behind positive implications on the adipose tissue of high-fat diet (HFD) mice
Summary
Obesity is abnormal fat accumulation in adipose tissues and characterized by body mass index (BMI) higher than 30 kg/m2 and is associated with multiple chronic diseases such as type 2 diabetes, cardiovascular disorders, and different types of cancers [1]. WAT loses its functional capabilities with obesity negatively affecting its storage of surplus energy. This process leads to ectopic fat accumulation in several tissues influencing metabolic homeostasis [2]. Visceral adipose tissue development by lowering lipogenesis and enhancing lipid oxidation could be a promising approach to treat obesity and associated metabolic dysfunction. We discovered that excessive reactive nitrogen species (RNS) build up during obesity, causing nitro-oxidative stress and triggering cysteine oxidation These processes induce alterations in ER membrane protein, IRE1α. Efforts are put to investigate the potential impact and mechanism behind the beneficial effects of IBF-R on obesity
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