RESUMO
Ciliary neurotrophic factor (CNTF) analogues were reported to ameliorate fatty liver in db/db or high-fat diet-fed mice. It is generally thought that CNTF exerts its actions centrally. The aim of this study was to investigate whether peripheral effects of CNTF analogues are involved in the therapeutic effect on high fat-induced hepatic steatosis. The rat model of fatty liver was induced by a high-fat diet (HFD) for 12 weeks. In the next 2 weeks, rats were fed the HFD along with subcutaneous injection of vehicle or mutant recombinant human CNTF (rhmCNTF 0.05-0.2 mg/kg per day). Steatotic HepG2 cells were induced by 50% fetal bovine serum (FBS) for 48 hours, and then treated with rhmCNTF for 24 hours. The results showed that after rhmCNTF treatment, hepatic triglyceride (TG) accumulation was attenuated both in vivo and in vitro. RhmCNTF increased protein expression of CPT-1 and PPARα, and decreased SREBP-1c, FAS and SCD-1 in steatotic HepG2 cells. But the production of nitric oxide and 8-isoPGF2α in steatotic HepG2 cells was not affected by rhmCNTF. These results suggest that rhmCNTF has a peripheral effect that alleviates fat-induced hepatic steatosis.
Assuntos
Fator Neurotrófico Ciliar/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Animais , Técnicas de Cultura de Células , Fator Neurotrófico Ciliar/administração & dosagem , Fator Neurotrófico Ciliar/genética , Dinoprosta/análogos & derivados , Dinoprosta/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Injeções Subcutâneas , Masculino , Óxido Nítrico/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ratos Sprague-Dawley , Proteínas Recombinantes , Triglicerídeos/metabolismoRESUMO
Metabolic syndrome (MS) is highly prevalent in developed countries and becoming a serious worldwide public health issue. In this study, we established a MS model by feeding male C57BL/6J mice with a high-fat diet (10%) for 18.5 weeks, studied the therapeutic effects of a recombinant mutant of the human ciliary neurotrophic factor (rhmCNTF) 0.1 (C-0.1) or 0.3 (C-0.3) mg x kg(-1) per day subcutaneously or pair feeding (PF, which mice were restricted to the same amount of food as eaten by C-0.3 treated mice) in MS mice. After 10 days treatment, rhmCNTF reduced obesity related indices, ameliorated glucose and lipid metabolism abnormality, and enhanced insulin sensitivity. In addition, liver function and antioxidant ability of MS mice were improved by rhmCNTF. Pair feeding revealed the same effects as C-0.3 on obesity related indices and insulin sensitivity, but aggravated hepatic steatosis and hepatic function. The results suggest that rhmCNTF could serve as an effective therapeutic agent for MS and related diseases.
Assuntos
Fator Neurotrófico Ciliar/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Glicemia/metabolismo , Fator Neurotrófico Ciliar/sangue , Dieta , Gorduras na Dieta , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/etiologia , Humanos , Resistência à Insulina , Lipídeos/sangue , Testes de Função Hepática , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/etiologia , Proteínas Recombinantes/uso terapêuticoRESUMO
The development of a three-dimensionally flexible, large-surface area, high-conductivity electrode is important to improve the low conductivity and utilization of active materials and restrict the shuttle of long-chain polysulfides in Li-polysulfide batteries. Herein, we constructed an integrated three-dimensional carbon nanotube forest/carbon cloth electrode with heteroatom doping and high electrical conductivity. The as-constructed electrode provides strong trapping on the polysulfide species and fast charge transfer. Therefore, the Li-polysulfide batteries with as-constructed electrodes achieved high specific capacities of â¼1200 and â¼800 mA h g-1 at 0.1 and 1 C, respectively. After 300 cycles at 0.5 C, a specific capacity of 623 mA h g-1 was retained.