ABSTRACT
Aim To investigate the effect of extracellular vesicles secreted by adipose tissue of mice on hippocampal neurons and cognitive behavior of mice with a high-fat diet.Methods Twenty C57BL/6J male mice were randomly divided into normal diet(ND)group(n=10)and high-fat diet(HFD)group(n=10), fed for 28 weeks.The weight of mice was recorded weekly.The level of fasting blood glucose, insulin and the insulin resistance index(HOMA-IR)of mice were tested at week 27.At week 28, the learning and memory abilities of mice were assessed by the Morris water maze.The morphological differences in adipose tissue were observed by HE staining, and the extracellular vesicles secreted from adipose tissue were quantified by TEM and NTA.Extracellular vesicles derived from adipose tissue labeled with PKH 67 were injected into normal mice via the tail vein, and after 30 h, the uptake of extracellular vesicles was detected in the hippocampal slice.The primary hippocampal neurons were treated with extracellular vesicles with the same amount of protein, and the effects of them on neuronal morphology and cell viability were observed.Results Compared with ND group, mice in HFD group were significantly heavier, with hyperglycemia, hyperinsulinemia and higher insulin resistance index.In the Morris water maze test, the HFD group showed a longer escape latency and less swimming time in the target zone.The volume of adipocytes and the amount of extracellular vesicles secreted from them significantly increased in HFD group.Extracellular vesicles secreted by adipose tissue could be internalized by both the primary hippocampal neurons and the hippocampal neurons in the normal mice.Compared with ND group, extracellular vesicles secreted by adipose tissue of the HFD group significantly reduced the length of primary hippocampal neuronal dendrites, the number of primary and secondary dendrites, and the cell viability of neuron cells.Conclusion Long-term high-fat diet could damage the hippocampal neurons by affecting the extracellular vesicles derived from adipose tissue.
ABSTRACT
Objective : Visfatin is a recently discovered adipocytokine that contributes to glucose and obesity-related conditions. Until now, its responses to the insulin-sensitizing agent metformin and to exercise are largely unknown. We aim to investigate the impact of metformin treatment and/or swimming exercise on serum visfatin and visfatin levels in subcutaneous adipose tissue (SAT), peri-renal adipose tissue (PAT) and skeletal muscle (SM) of high-fat-induced obesity rats. Materials and methods : Sprague-Dawley rats were fed a normal diet or a high-fat diet for 16 weeks to develop obesity model. The high-fat-induced obesity model rats were then randomized to metformin (MET), swimming exercise (SWI), or adjunctive therapy of metformin and swimming exercise (MAS), besides high-fat obesity control group and a normal control group, all with 10 rats per group. Zoometric and glycemic parameters, lipid profile, and serum visfatin levels were assessed at baseline and after 6 weeks of therapy. Visfatin levels in SAT, PAT and SM were determined by Western Blot. Results : Metformin and swimming exercise improved lipid profile, and increased insulin sensitivity and body weight reduction were observed. Both metformin and swimming exercise down-regulated visfatin levels in SAT and PAT, while the adjunctive therapy conferred greater benefits, but no changes of visfatin levels were observed in SM. Conclusion : Our results indicate that visfatin down-regulation in SAT and PAT may be one of the mechanisms by which metformin and swimming exercise inhibit obesity. .
Objetivo : A visfatina é uma adipocina recentemente descoberta que contribui com as condições relacionadas à glicose e à obesidade. Até hoje, pouco se sabe da sua resposta à metformina, um agente sensibilizador de insulina, e ao exercício. Nosso objetivo foi investigar o impacto do tratamento com metformina e/ou da natação sobre a visfatina no soro e no tecido adiposo subcutâneo (TAS), tecido adiposo perirrenal (TAP) e músculo esquelético (ME) em ratos com obesidade induzida por dieta com alto teor de gordura. Materiais e métodos : Ratos Sprague-Dawley foram alimentados com uma dieta normal ou com alto teor de gordura por 16 semanas para o desenvolvimento de um modelo de obesidade. Os ratos do modelo de obesidade foram, então, randomizados para a metformina, natação ou terapia de combinação com metformina e natação, além do grupo controle de obesidade induzida por alto teor de gordura e do grupo controle normal. Cada grupo apresentava 10 ratos. Parâmetros zoométricos e glicêmicos, perfil lipídico e níveis de visfatina sérica foram avaliados no momento inicial e após seis semanas de tratamento. Os níveis de visfatina em TAS, TAP e ME foram determinados por Western Blot. Resultados : A metformina e a natação melhoraram o perfil lipídico e aumentaram a sensibilidade à insulina, com redução do peso corporal. Tanto a metformina quanto a natação levaram à regulação para baixo dos níveis de visfatina no TAS e TAP, enquanto a terapia de combinação apresentou os maiores benefícios, mas não foram observadas alterações nos níveis de visfatina no ME. Conclusão : Nossos resultados indicam que a regulação para baixo da visfatina no TAS e TAP pode ser um dos mecanismos pelos quais a metformina ...