RESUMEN

Insulin resistance is thought to be a common link between obesity and Non-Alcoholic Fatty Liver Disease (NAFLD). NAFLD has now reached epidemic status worldwide and identification of molecules or pathways as newer therapeutic strategies either to prevent or overcome insulin resistance seems critical. Dysregulated hepatic lipogenesis (DNL) is a hallmark of NAFLD in humans and rodents. Therefore, reducing DNL accretion may be critical in the development of therapeutics of NAFLD. In our in vivo model (high-fat-diet fed [HFD] obese mice) we found Zinc oxide nanoparticles (ZnO NPs) significantly decreased HFD-induced hepatic steatosis and peripheral insulin resistance. This protective mechanism of ZnO NPs was signaled through hepatic SIRT1-LKB1-AMPK which restricted SREBP-1c within the cytosol limiting its transcriptional ability and thereby ameliorating HFD mediated DNL. These observations indicate that ZnO NP can serve as a therapeutic strategy to improve the physiological homeostasis during obesity and its associated metabolic abnormalities.

Asunto(s)

Proteínas Quinasas Activadas por AMP/metabolismo , Activadores de Enzimas/uso terapéutico , Nanopartículas/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Óxido de Zinc/uso terapéutico , Animales , Dieta Alta en Grasa/efectos adversos , Células Hep G2 , Humanos , Resistencia a la Insulina , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Transducción de Señal/efectos de los fármacos

RESUMEN

Despite its murderous act, carbon monoxide (CO) is found to be a very crucial small gaseous messenger molecule in dictating prime biological and physiological processes. Determination of endogenous or exhaled CO levels can throw significant light on smoking status and can be used as a breath biomarker of inflammatory diseases. Therefore, fluorescence imaging of CO in biofluids will empower one with the minute details of various disease states that involve CO. Unfortunately, such efficient fluorescent probes are less in number and also associated with tedious protocols. This enticed our attention and inspired us to look upon developing perceptive imaging agents for CO in a living system. In this report, a resorufin-based "turn-on" orange emissive molecular probe has been successfully utilized to detect CO in an aqueous system. The mono protection of a resorufin unit with an allyl chloroformate furnished a weakly fluorescent small molecular probe P1. Further, the P1+Pd2+ ensemble has been successfully developed in situ using PdCl2 (as Pd2+) and utilized as a light-up signaling mechanism tool for the sensing of CO at the nanomolar level (62 nM) through deprotection mechanism. The probe selectively detects CO without any interference from other anions, gasotransmitters and fatty acids. The present integrated probe P1+Pd2+ system has been found to be highly sensitive to detect CO in cellular systems as well.