Stanniocalcin 2 Ameliorates Hepatosteatosis Through Activation of STAT3 Signaling

Stanniocalcin 2 (STC2), a secreted glycoprotein hormone, regulates many biological processes, including cell proliferation, apoptosis, tumorigenesis, and atherosclerosis. However, its role in hepatic triglyceride metabolism remains unknown. In the present study, we found that expression levels of STC2 were significantly reduced in the livers of leptin-deficient and high fat diet-induced obese mice. Systemic administration of STC2 recombinant protein or adenovirus-mediated overexpression of STC2 markedly attenuated hepatosteatosis and hypertriglyceridemia in obese mice. At the molecular level, we found that STC2 activated the STAT3 signaling pathway to inhibit lipogenic gene expression. Consistently, in vitro studies further showed that inhibition of STAT3 signaling abolished the anti-steatotic effects of STC2. Together, our results revealed an important role of STC2 in the regulation of hepatic triglyceride metabolism, which might provide a potential therapeutic target for the treatment of fatty liver and related metabolic disorders

Fragile Treg cells: Traitors in immune homeostasis?

Regulatory T (Treg) cells play a key role in maintaining immune tolerance and tissue homeostasis. However, in some disease microenvironments, Treg cells exhibit fragility, which manifests as preserved FoxP3 expression accompanied by inflammation and loss of immunosuppression. Fragile Treg cells are formatively, phenotypically and functionally diverse in various diseases, further complicating the role of Treg cells in the immunotherapeutic response and offering novel targets for disease treatment by modulating specific Treg subsets. In this review, we summarize findings on fragile Treg cells to provide a framework for characterizing the formation and role of fragile Treg cells in different diseases, and we discuss how this information may guide the development of more specific Treg-targeted immunotherapies

Negative Density Restricts the Coexistence and Spatial Distribution of Dominant Species in Subtropical Evergreen Broad-Leaved Forests in China

Negative densification affects the spatial distribution of species in secondary evergreen broad-leaved forests and is a key mechanism governing species coexistence. We investigated the effects of habitat heterogeneity and density on the spatial distribution of populations of dominant woody species in a secondary evergreen broad-leaved forest in Wuchaoshan using spatial univariate point pattern analyses. This 6 ha forest dynamic monitoring sample area in Hangzhou, China is a typical secondary subtropical evergreen broad-leaved forest. We found (1) a strong effect of habitat heterogeneity that led to the spatial aggregation of dominant species in the plot. Habitat heterogeneity had a strong impact on mature individuals at different life history stages and of different species on a large scale. (2) Negative density dependence (NDD) generally affected spatial distributions of most dominant species and decreased in magnitude with age class. Therefore, different species of subtropical evergreen broad-leaved forests in China have formed unique spatial structures due to their habitat preferences but are generally subjected to density-dependent effects

Assessment of Species Composition and Community Structure of the Suburban Forest in Hangzhou, Eastern China

The forest community structure and dynamic structure provide basic data for in-depth study of the community maintenance mechanisms and succession processes of urban forest ecosystems. Moreover, the study on the dynamics of suburban forest communities can provide a reference for the succession process of forest communities under severe human disturbance. In this context, this study analyzes the species composition and community structure of a 6 ha subtropical secondary evergreen broad-leaved forest plot in Wuchaoshan National Forest Park, Hangzhou, Eastern China. There are 36,757 existing woody plants (with DBH ≥ 1 cm), belonging to 94 species (45 evergreen species, and 48 deciduous species) in 63 genera of 34 families, with a plant density of 6126 plants/ha. The overall size–class distribution shows an obvious inverted “J” shape. Species with the top-five important values in the sample are Schima superba, Camellia fraternal, Symplocos anomala, Cyclobalanopsis glauca, Eurya rubiginosa, accounting for 57.3% of all individuals within the sample. In addition, different species have different habitat preferences and different distribution areas. The Wuchaoshan forest is in the middle and late stages of the succession. Different interference histories in the community succession process are demonstrated through studies of secondary evergreen broad-leaved forests. Long-term community monitoring contributes to indicating the direction and potential of the secondary forest succession

Image_1_Stanniocalcin 2 Ameliorates Hepatosteatosis Through Activation of STAT3 Signaling.TIF

<p>Stanniocalcin 2 (STC2), a secreted glycoprotein hormone, regulates many biological processes, including cell proliferation, apoptosis, tumorigenesis, and atherosclerosis. However, its role in hepatic triglyceride metabolism remains unknown. In the present study, we found that expression levels of STC2 were significantly reduced in the livers of leptin-deficient and high fat diet-induced obese mice. Systemic administration of STC2 recombinant protein or adenovirus-mediated overexpression of STC2 markedly attenuated hepatosteatosis and hypertriglyceridemia in obese mice. At the molecular level, we found that STC2 activated the STAT3 signaling pathway to inhibit lipogenic gene expression. Consistently, in vitro studies further showed that inhibition of STAT3 signaling abolished the anti-steatotic effects of STC2. Together, our results revealed an important role of STC2 in the regulation of hepatic triglyceride metabolism, which might provide a potential therapeutic target for the treatment of fatty liver and related metabolic disorders.</p

Image_2_Stanniocalcin 2 Ameliorates Hepatosteatosis Through Activation of STAT3 Signaling.TIF

<p>Stanniocalcin 2 (STC2), a secreted glycoprotein hormone, regulates many biological processes, including cell proliferation, apoptosis, tumorigenesis, and atherosclerosis. However, its role in hepatic triglyceride metabolism remains unknown. In the present study, we found that expression levels of STC2 were significantly reduced in the livers of leptin-deficient and high fat diet-induced obese mice. Systemic administration of STC2 recombinant protein or adenovirus-mediated overexpression of STC2 markedly attenuated hepatosteatosis and hypertriglyceridemia in obese mice. At the molecular level, we found that STC2 activated the STAT3 signaling pathway to inhibit lipogenic gene expression. Consistently, in vitro studies further showed that inhibition of STAT3 signaling abolished the anti-steatotic effects of STC2. Together, our results revealed an important role of STC2 in the regulation of hepatic triglyceride metabolism, which might provide a potential therapeutic target for the treatment of fatty liver and related metabolic disorders.</p

Paternal Psychological Stress Reprograms Hepatic Gluconeogenesis in Offspring

Both epidemiologic and experimental animal studies demonstrate that chronic psychological stress exerts adverse effects on the initiation and/or progression of many diseases. However, intergenerational effects of this environmental information remains poorly understood. Here, using a C57BL/6 mouse model of restraint stress, we show that offspring of stressed fathers exhibit hyperglycemia due to enhanced hepatic gluconeogenesis and elevated expression of PEPCK. Mechanistically, we identify an epigenetic alteration at the promoter region of the Sfmbt2 gene, a maternally imprinted polycomb gene, leading to a downregulation of intronic microRNA-466b-3p, which post-transcriptionally inhibits PEPCK expression. Importantly, hyperglycemia in F1 mice is reversed by RU486 treatment in fathers, and dexamethasone administration in F0 mice phenocopies the roles of restraint stress. Thus, we provide evidence showing the effects of paternal psychological stress on the regulation of glucose metabolism in offspring, which may have profound implications for our understanding of health and disease risk inherited from fathers