RESUMEN
The mechanisms connecting obesity with type 2 diabetes, insulin resistance, nonalcoholic fatty liver disease, and cardiovascular diseases remain incompletely understood. The function of MAPK phosphatase-2 (MKP-2), a type 1 dual-specific phosphatase (DUSP) in whole-body metabolism, and how this contributes to the development of diet-induced obesity, type 2 diabetes (T2D), and insulin resistance is largely unknown. We investigated the physiological contribution of MKP-2 in whole-body metabolism and whether MKP-2 is altered in obesity and human fatty liver disease using MKP-2 knockout mice models and human liver tissue derived from fatty liver disease patients. We demonstrate that, for the first time, MKP-2 expression was upregulated in liver tissue in humans with obesity and fatty liver disease and in insulin-responsive tissues in mice with obesity. MKP-2-deficient mice have enhanced p38 MAPK, JNK, and ERK activities in insulin-responsive tissues compared with wild-type mice. MKP-2 deficiency in mice protects against diet-induced obesity and hepatic steatosis and was accompanied by improved glucose homeostasis and insulin sensitivity. Mkp-2-/- mice are resistant to diet-induced obesity owing to reduced food intake and associated lower respiratory exchange ratio. This was associated with enhanced circulating insulin-like growth factor-1 (IGF-1) and stromal cell-derived factor 1 (SDF-1) levels in Mkp-2-/- mice. PTEN, a negative regulator of Akt, was downregulated in livers of Mkp-2-/- mice, resulting in enhanced Akt activity consistent with increased insulin sensitivity. These studies identify a novel role for MKP-2 in the regulation of systemic metabolism and pathophysiology of obesity-induced insulin resistance and fatty liver disease.
Asunto(s)
Diabetes Mellitus Tipo 2 , Hígado Graso , Resistencia a la Insulina , Animales , Diabetes Mellitus Tipo 2/metabolismo , Fosfatasa 1 de Especificidad Dual/metabolismo , Fosfatasas de Especificidad Dual , Hígado Graso/metabolismo , Humanos , Insulina/metabolismo , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fosfatasas de la Proteína Quinasa Activada por Mitógenos , Obesidad/metabolismo , Proteínas Tirosina Fosfatasas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Regulación hacia ArribaRESUMEN
Obesity has reached global epidemic proportions and it affects the development of insulin resistance, type 2 diabetes, fatty liver disease and other metabolic diseases. Membrane lipids are important structural and signaling components of the cell membrane. Recent studies highlight their importance in lipid homeostasis and are implicated in the pathogenesis of fatty liver disease. Here, we discuss the numerous membrane lipid species and their metabolites including, phospholipids, sphingolipids and cholesterol, and how dysregulation of their composition and physiology contribute to the development of fatty liver disease. The development of new genetic and pharmacological mouse models has shed light on the role of lipid species on various mechanisms/pathways; these lipids impact many aspects of the pathophysiology of fatty liver disease and could potentially be targeted for the treatment of fatty liver disease.
RESUMEN
Solid-state lithium batteries are generally considered as the next-generation battery technology that benefits from inherent nonflammable solid electrolytes and safe harnessing of high-capacity lithium metal. Among various solid-electrolyte candidates, cubic garnet-type Li7La3Zr2O12 ceramics hold superiority due to their high ionic conductivity (10-3 to 10-4 S cm-1) and good chemical stability against lithium metal. However, practical deployment of solid-state batteries based on such garnet-type materials has been constrained by poor interfacing between lithium and garnet that displays high impedance and uneven current distribution. Herein, we propose a facile and effective strategy to significantly reduce this interfacial mismatch by modifying the surface of such garnet-type solid electrolyte with a thin layer of silicon nitride (Si3N4). This interfacial layer ensures an intimate contact with lithium due to its lithiophilic nature and formation of an intermediate lithium-metal alloy. The interfacial resistance experiences an exponential drop from 1197 to 84.5 Ω cm2. Lithium symmetrical cells with Si3N4-modified garnet exhibited low overpotential and long-term stable plating/stripping cycles at room temperature compared to bare garnet. Furthermore, a hybrid solid-state battery with Si3N4-modified garnet sandwiched between lithium metal anode and LiFePO4 cathode was demonstrated to operate with high cycling efficiency, excellent rate capability, and good electrochemical stability. This work represents a significant advancement toward use of garnet solid electrolytes in lithium metal batteries for the next-generation energy storage devices.
RESUMEN
Perovskites have been unprecedented with a relatively sharp rise in power conversion efficiency in the last decade. However, the polycrystalline nature of the perovskite film makes it susceptible to surface and grain boundary defects, which significantly impedes its potential performance. Passivation of these defects has been an effective approach to further improve the photovoltaic performance of the perovskite solar cells. Here, we report the use of a novel hydrazine-based aromatic iodide salt or phenyl hydrazinium iodide (PHI) for secondary post treatment to passivate surface and grain boundary defects in triple cation mixed halide perovskite films. In particular, the PHI post treatment reduced current at the grain boundaries, facilitated an electron barrier, and reduced trap state density, indicating suppression of leakage pathways and charge recombination, thus passivating the grain boundaries. As a result, a significant enhancement in power conversion efficiency to 20.6% was obtained for the PHI-treated perovskite device in comparison to a control device with 17.4%.