The status of ω-3 PUFAs influence chronic unpredicted mild stress-induced metabolic side effects in rats through INSIG/SREBP pathway.

Abstract

Metabolic disturbances, including lipid metabolism, bone metabolism, and glycometabolism, are common in depression. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), which are reported to possess antidepressant effect, have also been shown to regulate metabolism. To further clarify the potential link between ω-3 PUFAs and stress-induced metabolic disturbances, metabolic-related parameters including body weight, visceral fat, fatty acid composition and serum parameters, such as serum lipids, free fatty acid (FFA), glucose (GLU), calcium and phosphorus in rats were measured. Moreover, hepatic insulin induced gene (INSIG)/sterol regulatory element binding protein (SREBP) pathway was also investigated. After 5 weeks of chronic unpredicted mild stress (CUMS) administration, rats were induced to a depressive-like state and exhibited decreased serum high-density lipoprotein (HDL-c), body weight and visceral fat, accompanied by altered C18:2n6c and ω-3/ω-6 PUFAs. Supplement of ω-3 PUFAs showed robust antidepressant effects and has beneficial effects on lipid profile. On the contrary, ω-3 PUFAs deficiency induced the visceral fat accumulation and decreased the serum calcium and phosphorus in stressed rats. Additionally, CUMS significantly increased hepatic expressions of SREBP-cleavage activating protein (SCAP)/SREBP-1 and decreased the expression of INSIG-1. This disturbance of SREBPs system is aggravated by ω-3 PUFAs deficiency and alleviated by ω-3 PUFAs supplementation. This study discloses the novel findings that ω-3 PUFAs deficiency will exacerbate the metabolic disturbances in stressed rats. Furthermore, supplementation of ω-3 PUFAs on individuals with a high risk of depression might be an effective way to prevent metabolic disorders accompanied by depression with the involvement of INSIG/SREBP pathway.