Salubrinal abrogates palmitate-induced leptin resistance and endoplasmic reticulum stress via nuclear factor kappa-light-chain-enhancer of activated B cell pathway in mHypoE-44 hypothalamic neurons

Abstract

Min Zhang,1 Xiaohong Jiang,2 Meidi Qu,1 Hongliu Gu,1 Qi Sha,1 Fei Hua2 1Department of Clinical Nutrition, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, China; 2Department of Endocrinology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, China Background: The prevalence of obesity is growing rapidly and has become a global problem that increases the risk for many diseases. It is influenced by many factors, including consumption of the Western-style diet, characterized as a high-fat diet. Within the central nervous system, the hypothalamus is a critical site in maintaining energy homeostasis and sensing nutrient status, including palmitate, the major component of high-fat-diet.Methods: In the present study, we conducted a variety of studies to investigate the specific role of salubrinal on palmitate-induced hypothalamic cell death, leptin signaling, and ER stress in an embryonic hypothalamic cell line. Experiments were also performed to identify the underlying mechanisms of the protective effect of salubrinal.Results: Our results indicate that salubrinal protects hypothalamic cells against PA-induced ER stress and improves hypothalamic leptin sensitivity. Conclusion: Taken together, our findings conclusively reveal that salubrinal abrogates palmitate-induced hypothalamic leptin resistance and ER stress via NF-κB pathway. Keywords: obesity, high-fat diet, palmitate, leptin resistance, ER stress, salubrinal

Keywords

• Obesity
• High-fat-diet
• Palmitate
• Leptin resistance
• ER stress
• Salubrinal