The effects of myostatin on adipogenic differentiation are poorly understood, and the underlying mechanisms are unknown. We determined the effects of human recombinant myostatin protein on adipogenesis of bone marrow-derived human mesenchymal stem cells (hMSCs) and adipose tissuederived preadipocytes. For both progenitor cell types, differentiation in the presence of myostatin caused a dose-dependent reduction of lipid accumulation and diminished incorporation of exogenous fatty acid into cellular lipids. Myostatin significantly down-regulated the expression of adipocyte markers PPAR␥, C/EBP␣, leptin, and aP2, but not C/EBP␤. Overexpression of PPAR␥, but not C/EBP␤, blocked the inhibitory effects of myostatin on adipogenesis. Myostatin induced phosphorylation of Smad3 in hMSCs; knockdown of Smad3 by RNAi or inhibition of its upstream kinase by an Alk5 inhibitor blocked the inhibitory effect of myostatin on adipogenesis in hMSCs, implying an important role of Smad3 activation in this event. Furthermore, myostatin enhanced nuclear translocation of ␤-catenin and formation of the Smad3-␤-catenin-TCF4 complex, together with the altered expression of a number of Wnt/␤-catenin pathway genes in hMSCs. The inhibitory effects of myostatin on adipogenesis were blocked by RNAi silencing of ␤-catenin and diminished by overexpression of dominant-negative TCF4. The conclusion is that myostatin inhibited adipogenesis in human bone marrow-derived mesenchymal stem cells and preadipocytes. These effects were mediated, in part, by activation of Smad3 and cross-communication of the TGF␤/Smad signal to Wnt/␤-catenin/TCF4 pathway, leading to down-regulation of PPAR␥.Whereas the role of myostatin in the regulation of skeletal muscle mass in animals has been widely recognized (1-8), its effects on adipogenesis are poorly understood. Inactivating mutations of the myostatin gene in a number of mammalian species are associated with hypermuscularity and decreased fat mass (9 -13). Similarly, myostatin knockout mice are characterized by a lower fat mass than wild-type controls (14, 15). These in vivo observations have led to speculation that myostatin promotes adipogenesis. However, the data on the effects of myostatin on fat mass and metabolism are conflicting. Transgenic mice that hyperexpress myostatin protein either systemically or in the skeletal muscle have increased fat mass (5), whereas adipose-specific hyperexpression of myostatin leads to reduced fat mass and improved insulin sensitivity (16). Mice bearing tumor cells that hyperexpress myostatin experience loss of lean as well as fat mass (17); it is unclear whether the loss of fat mass is a consequence of myostatin hyperexpression or the tumor-associated cachexia.In vitro studies using various cell lines also have yielded inconsistent results. Some studies have reported that myostatin inhibits adipogenic differentiation of adipocyte precursor cell lines of murine, bovine, and human origins (16,18,19), whereas others have reported promotion of adipogenic differentiation by recombin...

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Catalytic hydrogenolysis of biomass-derived glycerol to 1,3-propanediol (1,3-PDO) represents an important process for the sustainable production of value-added chemicals. However, there is a dearth of understanding of the effect of the polymorph of the support on this reaction. Herein, two Pt–WO x /TiO2 catalysts supported on rutile TiO2 (r-TiO2) and anatase TiO2 (a-TiO2) polymorphs were prepared to investigate the crystal phase effect of TiO2 on the structural property and catalytic performance in glycerol hydrogenolysis. The TiO2 polymorph was identified to impose profound effects on the size of the Pt nanoparticles (NPs) and the dispersion and location of the WO x species, which originated from the discrepancies in the crystal structures between the PtO2 and the TiO2 polymorphs and the discrepancies in the interactions of WO x with different TiO2 polymorphs. In glycerol hydrogenolysis, the Pt–WO x /r-TiO2 catalyst gave a 1,3-PDO selectivity of 51.2% at a glycerol conversion to liquid products of 74.5%, yielding 38.1% of 1,3-PDO. In contrast, the Pt–WO x /a-TiO2 catalyst showed much inferior glycerol conversion and 1,3-PDO selectivity, yielding only 1.0% of 1,3-PDO under identical reaction conditions. The superior catalytic performance of the Pt–WO x /r-TiO2 catalyst is attributed to the r-TiO2 polymorph that facilitates a faster hydrogen spillover than the a-TiO2 polymorph from the Pt NPs to the reaction intermediate on the WO x species, which is substantiated by an even higher 1,3-PDO yield of 44.8% over the physically mixed Pt/r-TiO2 + WO x /r-TiO2 catalyst. This work demonstrates the critical role of the polymorph of the TiO2 support in the design of efficacious Pt–WO x -based catalysts for glycerol hydrogenolysis to 1,3-PDO.

Acute kidney injury (AKI) is a common clinical problem and an efficacious treatment is lacking. Ferroptosis, a newly discovered type of programmed cell death, has been reported to alleviate renal tubular injury in ischemia/reperfusion‐induced acute kidney injury (I/R‐AKI). Entacapone is a specific inhibitor of catechol‐O‐methyltransferase, which is used as an adjuvant drug against Parkinson's disease. We demonstrated that entacapone prevents renal I/R injury by inhibiting ferroptosis. Compared with a sham group, entacapone treatment mitigated I/R‐induced pathological alterations, improved renal function, and inhibited ferroptosis. In HK‐2 cells, entacapone treatment significantly reduced the lipid peroxidation and iron accumulation induced by the ferroptosis inducers erastin and RSL3, and significantly regulated expression of ferroptosis‐related proteins. Entacapone upregulates p62 expression and affects the p62‐KEAP1‐NRF2 pathway, thereby upregulating nuclear translocation of NRF2. This action results in increased expression of the downstream SLC7A11, and significant suppression of oxidative stress and ferroptosis. Our results identify entacapone as a ferroptosis inhibitor that enhances antioxidant capacity. Entacapone may serve as a novel strategy to improve treatment of, and recovery from, I/R‐AKI.

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