[Chronic psychological stress exacerbates aortic medial calcification via glucocorticoids].

Chronic psychological stress can promote vascular diseases, such as hypertension and atherosclerosis. This study aims to explore the effects and mechanism of chronic psychological stress on aortic medial calcification (AMC). Rat arterial calcification model was established by nicotine gavage in combination with vitamin D3 (VitD3) intramuscular injection, and rat model of chronic psychological stress was induced by humid environment. Aortic calcification in rats was evaluated by using Alizarin red staining, aortic calcium content detection, and alkaline phosphatase (ALP) activity assay. The expression levels of the related proteins, including vascular smooth muscle cells (VSMCs) contractile phenotype marker SM22α, osteoblast-like phenotype marker RUNX2, and endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP), were determined by Western blot. The results showed that chronic psychological stress alone induced AMC in rats, further aggravated AMC induced by nicotine in combination with VitD3, promoted the osteoblast-like phenotype transformation of VSMCs and aortic ERS activation, and significantly increased the plasma cortisol levels. The 11ß-hydroxylase inhibitor metyrapone effectively reduced chronic psychological stress-induced plasma cortisol levels and ameliorated AMC and aortic ERS in chronic psychological stress model rats. Conversely, the glucocorticoid receptor agonist dexamethasone induced AMC, promoted AMC induced by nicotine combined with VitD3, and further activated aortic ERS. The above effects of dexamethasone could be inhibited by ERS inhibitor 4-phenylbutyrate. These results suggest that chronic psychological stress can lead to the occurrence and development of AMC by promoting glucocorticoid synthesis, which may provide new strategies and targets for the prevention and control of AMC.

Betulinic acid improves nonalcoholic fatty liver disease through YY1/FAS signaling pathway.

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide indicates the urgent need to develop novel and effective treatment strategies. Betulinic acid (BA), a naturally occurring plant-derived pentacyclic triterpenoid, has an outstanding effect in improving metabolism. However, the pharmacological action and mechanism of BA in NAFLD remain unclear. Here, we show that BA-treated high-fat diet mice and methionine-choline deficient diet-fed mice are resistant to hepatic steatosis when compared with vehicle-treated mice. BA alleviates fatty acid synthesis, fibrosis, and inflammation and promotes fatty acid oxidation. Meanwhile, fatty acid synthase (FAS) expression and activity are markedly inhibited with BA treatment both in vitro and in vivo. Moreover, BA inhibits FAS expression through transcriptional suppression of Yin Yang 1 (YY1), leading to retard hepatocytes triglyceride accumulation. Collectively, BA protects hepatocytes from abnormal lipid deposition in NAFLD through YY1/FAS pathway. Our findings establish a novel role of BA in representing a possible therapeutic strategy to reverse NAFLD.

First report of the ectomycorrhizal fungal community associated with two herbaceous plants in Inner Mongolia, China.

Ectomycorrhizal (EM) fungi play a vital role in ensuring plant health, plant diversity, and ecosystem function. However, the study on fungal diversity and community assembly of EM fungi associated with herbaceous plants remains poorly understood. Thus, in our study, Carex pediformis and Polygonum divaricatum in the subalpine meadow of central Inner Mongolia, China were selected for exploring EM fungal diversity and community assembly mechanisms by using llumina MiSeq sequencing of the fungal internal transcribed spacer 2 region (ITS2). We evaluated the impact of soil, climatic, and spatial variables on EM fungal diversity and community turnover. Deterministic vs. stochastic processes for EM fungal community assembly were quantified using ß-Nearest taxon index scores. The results showed that a total of 70 EM fungal OTUs belonging to 21 lineages were identified, of which Tomentella-Thelephora, Helotiales1, Tricholoma, Inocybe, Wilcoxina were the most dominant EM fungal lineages. EM fungal communities were significantly different between the two herbaceous plants and among the two sampling sites, and this difference was mainly influenced by soil organic matter (OM) content and mean annual precipitation (MAP). The neutral community model (NCM) explained 45.7% of the variations in EM fungi community assembly. A total of 99.27% of the ß-Nearest Taxa Index (ßNTI) value was between -2 and 2. These results suggest that the dominant role of stochastic processes in shaping EM fungal community assembly. In addition, RCbray values showed that ecological drift in stochastic processes dominantly determined community assembly of EM fungi. Overall, our study shed light on the EM fungal diversity and community assembly associated with herbaceous plants in the subalpine region of central Inner Mongolia for the first time, which provided a better understanding of the role of herbaceous EM fungi.

Erratum: Aquaporin-8 ameliorates hepatic steatosis through farnesoid X receptor in obese mice.

[This corrects the article DOI: 10.1016/j.isci.2023.106561.].

Aquaporin-8 ameliorates hepatic steatosis through farnesoid X receptor in obese mice.

Aquaporin-8(AQP8), is a transmembrane channel protein that abounds in liver, which mainly promotes water transport, modulating bile acid formation. However, its role in hepatic lipid metabolism remains unclear. In this study, we found the expression of AQP8 was reduced in liver specimens of patients with NAFLD, high-fat diet (HFD)-induced mice and genetically obese db/db mice. Knockdown of AQP8 in hepatocytes exacerbated the intracellular lipid accumulation induced by free fatty acid (FFA) mixtures. In contrast, hepatic AQP8 overexpression activated farnesoid X receptor (FXR), inhibiting gene expression associated with lipogenesis, which further reduced intrahepatic triglyceride overload in obese mice. FXR knockout abrogated the ameliorating effect of AQP8 overexpression on NAFLD in mice. These findings indicate that AQP8 overexpression protects against fatty liver through activating the FXR pathway.

miR-129-5p Inhibits Adipogenesis through Autophagy and May Be a Potential Biomarker for Obesity.

INTRODUCTION: Obesity has an unclear pathogenesis. MicroRNAs (miRNAs) may function as biologically active molecules for obesity through regulating adipocyte differentiation. This study aimed to identify how miR-129-5p (a specific miRNA) regulates adipogenesis in vitro and explore its possible role in the pathogenesis of obesity in humans. MATERIALS AND METHODS: The miR-129-5p expression was detected in obese mouse models. The effect of miR-129-5p on adipocyte differentiation was observed, and the adipose markers were analyzed. Bioinformatics and dual-luciferase reporter assay were applied to predict and confirm the target genes of miR-129-5p. The human serum samples were detected and analyzed. RESULTS: miR-129-5p is highly expressed in adipose tissues of db/db mice. Gain- and loss-of-function studies show that miR-129-5p could significantly inhibit adipocyte differentiation and white adipocyte browning in vitro and decreases the level of specific markers, such as FABP4, UCP1, and PPARγ, in mature white and brown adipocytes. miR-129-5p directly targets ATG7 which is predicted with bioinformatics and confirmed by dual-luciferase reporter assay. Serum miR-129-5p level was evidently elevated in patients with simple obesity (p < 0.01) and correlates with obesity indices, including BMI (r = 0.407, p < 0.029) and fat percentage (r = 0.394, p < 0.038). CONCLUSION: miR-129-5p might target on the ATG7-related autophagy signaling network that regulates white and brown adipogenesis. Importantly, the aforementioned results suggest serum miR-129-5p might be a potential biomarker and therapeutic target for obesity.