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Transforming growth factor beta (TGF-β) signaling in hepatocytes promotes steatosis and body weight gain. However, processes that TGF-β signaling in hepatocytes promote pathological body weight gain in nonalcoholic fatty liver disease (NAFLD) are incompletely understood. Obesity and NAFLD were induced by 16 weeks of feeding a high-fat diet (HFD) in hepatocyte-specific TGF-β receptor II-deficient (Tgfbr2ΔHEP ) and Tgfbr2flox/flox mice. In addition, browning of white adipose tissue (WAT) was induced by administration of CL-316,243 (a β3-adrenergic agonist) or cold exposure for 7 days. Compared with Tgfbr2 flox/flox mice, Tgfbr2ΔHEP mice were resistant to steatosis and obesity. The metabolic changes in Tgfbr2ΔHEP mice were due to the increase of mitochondrial oxidative phosphorylation in the liver and white-to-beige fat conversion. A further mechanistic study revealed that exosomal let-7b-5p derived from hepatocytes was robustly elevated after stimulation with palmitic acid and TGF-β. Indeed, let-7b-5p levels were low in the liver, serum exosomes, inguinal WAT, and epididymal WAT in HFD-fed Tgfbr2ΔHEP mice. Moreover, 3T3-L1 cells internalized hepatocyte-derived exosomes. An in vitro experiment demonstrated that let-7b-5p overexpression increased hepatocyte fatty acid transport and inhibited adipocyte-like cell thermogenesis, whereas let-7b-5p inhibitor exerted the opposite effects. Conclusion: Hepatocyte TGF-β-let-7b-5p signaling promotes HFD-induced steatosis and obesity by reducing mitochondrial oxidative phosphorylation and suppressing white-to-beige fat conversion. This effect of hepatocyte TGF-β signaling in metabolism is partially associated with exosomal let-7b-5p.

Iron or its oxides (FexOy) commonly exist in the ash of fossil fuel and biomass, and are used as oxygen carriers in chemical looping process, and Fe3O4 is a main occurrence. The NO reduction mechanisms by CO over Fe3O4 (111) surface was investigated via density functional theory (DFT) calculations. An optimized unit cell of Fe3O4 was constructed. The interaction between molecules and cell surface was described by the calculated adsorption properties and electronic structures. Results showed that the most stable adsorption of NO/CO belongs to chemisorption and NO has higher adsorption energy than CO. NO can be absorbed onto Fe3O4 surface to form (NO)2 dimer structure, which easily decomposes via a small energy barrier. (NO)2 dimer mechanism is a possible pathway for the reduction of NO by CO over Fe3O4, following three steps: 2NO → (NO)2*, (NO)2* → N2O + O*, O* + CO* → CO2. After the decomposition, the intermediate species N2O molecule and the remaining O atom adsorbed strongly on the Fe3O4 surface can be removed by CO. CO also promotes the gaseous decomposition of N2O. DFT results also showed O2 will prevent NO reduction reaction. The calculated reaction rate constants further verify the existence of (NO)2 dimer mechanism and the rate-limiting step is the removal of the surface O atom. [ABSTRACT FROM AUTHOR]