RESUMEN
INTRODUCTION AND OBJECTIVES: The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing. Previous studies indicated that Liraglutide, glucagon-like peptide-1 analogue, could regulate glucose homeostasis as a valuable treatment for Type 2 Diabetes. However, the precise effect of Liraglutide on NAFLD model in rats and the mechanism remains unknown. In this study, we investigated the molecular mechanism by which Liraglutide ameliorates hepatic steatosis in a high-fat diet (HFD)-induced rat model of NAFLD in vivo and in vitro. MATERIALS AND METHODS: NALFD rat models and hepatocyte steatosis in HepG2 cells were induced by HFD and palmitate fatty acid treatment, respectively. AMPK inhibitor, Compound C was added in HepG2 cells. Autophagy-related proteins LC3, Beclin1 and Atg7, and AMPK pathway-associated proteins were evaluated by Western blot and RT-PCR. RESULTS: Liraglutide enhanced autophagy as showed by the increased expression of the autophagy markers LC3, Beclin1 and Atg7 in HFD rats and HepG2 cells treated with palmitate fatty acid. In vitro, The AMPK inhibitor exhibited an inhibitory effect on Liraglutide-induced autophagy enhancement with the deceased expression of LC3, Beclin1 and Atg7. Additionally, Liraglutide treatment elevated AMPK levels and TSC1, decreased p-mTOR expression. CONCLUSIONS: Liraglutide could upregulate autophagy to decrease lipid over-accumulation via the AMPK/mTOR pathway.
Asunto(s)
Autofagia/efectos de los fármacos , Liraglutida/farmacología , Hígado/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Adenilato Quinasa/efectos de los fármacos , Adenilato Quinasa/metabolismo , Animales , Autofagia/genética , Proteína 7 Relacionada con la Autofagia/efectos de los fármacos , Proteína 7 Relacionada con la Autofagia/genética , Proteína 7 Relacionada con la Autofagia/metabolismo , Beclina-1/efectos de los fármacos , Beclina-1/genética , Beclina-1/metabolismo , Dieta Alta en Grasa , Células Hep G2 , Humanos , Técnicas In Vitro , Hígado/metabolismo , Proteínas Asociadas a Microtúbulos/efectos de los fármacos , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Palmitatos/farmacología , Ratas , Serina-Treonina Quinasas TOR/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Proteína 1 del Complejo de la Esclerosis Tuberosa/efectos de los fármacos , Proteína 1 del Complejo de la Esclerosis Tuberosa/metabolismoRESUMEN
Molecular Co4 O4 cubane water oxidation catalysts were combined with BiVO4 electrodes for photoelectrochemical (PEC) water splitting. The results show that tuning the substituent groups on cobalt cubane allows the PEC properties of the final molecular catalyst/BiVO4 hybrid photoanodes to be tailored. Upon loading a new cubane complex featuring alkoxy carboxylato bridging ligands (1 h) on BiVO4 , an AMâ 1.5G photocurrent density of 5â mA cm-2 at 1.23â V vs. RHE for water oxidation was obtained, the highest photocurrent for undoped BiVO4 photoanodes. A high solar-energy conversion efficiency of 1.84 % was obtained for the integrated photoanode, a sixfold enhancement over that of unmodified BiVO4 . These results and the high surface charge separation efficiency support the role of surface-modified molecular catalysts in improving PEC performance and demonstrate the potential of molecule/semiconductor hybrids for efficient artificial photosynthesis.