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

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.