Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling.

OBJECTIVE: Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs; however, concerns regarding complexities and side effects persist, driving research for more effective, low-risk strategies. The promotion of white adipose tissue (WAT) browning has emerged as a promising approach. Moreover, alisol B 23-acetate (AB23A) has demonstrated efficacy in addressing metabolic disorders, suggesting its potential as a therapeutic agent in obesity management. Therefore, in this study, we aimed to investigate the therapeutic potential of AB23A for mitigating obesity by regulating metabolic phenotypes and lipid distribution in mice fed a high-fat diet (HFD). METHODS: An obesity mouse model was established by administration of an HFD. Glucose and insulin metabolism were assessed via glucose and insulin tolerance tests. Adipocyte size was determined using hematoxylin and eosin staining. The expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain reaction. Metabolic cage monitoring involved the assessment of various parameters, including food and water intake, energy metabolism, respiratory exchange rates, and physical activity. Moreover, oil red O staining was used to evaluate intracellular lipid accumulation. A bioinformatic analysis tool for identifying the molecular mechanisms of traditional Chinese medicine was used to examine AB23A targets and associated signaling pathways. RESULTS: AB23A administration significantly reduced the weight of obese mice, decreased the mass of inguinal WAT, epididymal WAT, and perirenal adipose tissue, improved glucose and insulin metabolism, and reduced adipocyte size. Moreover, treatment with AB23A promoted the expression of browning markers in WAT, enhanced overall energy metabolism in mice, and had no discernible effect on food intake, water consumption, or physical activity. In 3T3-L1 cells, AB23A inhibited lipid accumulation, and both AB23A and rapamycin inhibited the mammalian target of rapamycin-sterol regulatory element-binding protein-1 (mTOR-SREBP1) signaling pathway. Furthermore, 3-isobutyl-1-methylxanthine, dexamethasone and insulin, at concentrations of 0.25 mmol/L, 0.25 µmol/L and 1 µg/mL, respectively, induced activation of the mTOR-SREBP1 signaling pathway, which was further strengthened by an mTOR activator MHY1485. Notably, MHY1485 reversed the beneficial effects of AB23A in 3T3-L1 cells. CONCLUSION: AB23A promoted WAT browning by inhibiting the mTOR-SREBP1 signaling pathway, offering a potential strategy to prevent obesity. Please cite this article as: Han LL, Zhang X, Zhang H, Li T, Zhao YC, Tian MH, Sun FL, Feng B. Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling. J Integr Med. 2024; 22(1): 83-92.

Arbuscular Mycorrhizal Fungi Shift Soil Bacterial Community Composition and Reduce Soil Ammonia Volatilization and Nitrous Oxide Emissions.

Arbuscular mycorrhizal fungi (AMF) establish mutualistic relationships with the majority of terrestrial plants, increasing plant uptake of soil nitrogen (N) in exchange for photosynthates. And may influence soil ammonia (NH3) volatilization and nitrous oxide (N2O) emissions directly by improving plant N uptake, and/or indirectly by modifying soil bacterial community composition for the soil C availability increasing. However, the effects of AMF on soil NH3 volatilization and N2O emissions and their underlying mechanisms remain unclear. We carried out two independent experiments using contrasting methods, one with a compartmental box device (in 2016) and the other with growth pot experiment (in 2020) to examine functional relationships between AMF and soil NH3 volatilization and N2O emissions under varying N input. The presence of AMF significantly reduced soil NH3 volatilization and N2O emissions while enhancing plant biomass and plant N acquisition, and reducing soil NH4+ and NO3-, even with high N input. The presence of AMF also significantly reduced the relative abundance within the bacterial orders Sphingomonadales and Rhizobiales. Sphingomonadales correlated significantly and positively with soil NH3 volatilization in 2016 and N2O emissions, whereas Rhizobiales correlated positively with soil N2O emissions. High N input significantly increased soil NH3 volatilization and N2O emissions with increasing relative abundance of Sphingomonadales and Rhizobiales. These findings demonstrate the contribution of AMF in regulating NH3 and N2O emission by improving plant N uptake and altering soil bacterial communities. They also suggest that altering the rhizosphere microbiome might offer additional potential for restoration of N-enriched agroecosystems.

Ruthenium tris(σ-B-H) borate complexes: synthesis, structure, and reactivity.

The coordination of the B-H bond to a transition metal is fundamentally intriguing due to its connection with the transition metal-mediated B-H bond activation mechanism and catalysis. Most of the reported examples are σ-borane/borate complexes containing one or two σ-B-H bonds. However, examples of compounds containing three σ-B-H bonds are still much rarer. Herein, we report a facile approach for the synthesis of rare transition metal tris(σ-B-H) borate complexes by the salt elimination protocol using [Cp*RuCl]4 and lithium trihydroborates Li[ArBH3] containing 2,6-disubstituted aryl groups. These complexes have remarkable thermal stability in solution. In addition, this novel class of compounds has the unusual σ-complex that features three labile σ-B-H bonds. Our studies on these new species demonstrate that the coordination σ-B-H bond can undergo H/D exchange with D2 and ligand substitution reactions with PPh3, PCy3 and IPr2Me2. These results provide new approaches for the synthesis of both tris(σ-B-H) borates and bis(σ-B-H) borates.

Jian Pi Tiao Gan Yin alleviates obesity phenotypes through mTORC1/SREBP1 signaling in vitro and in vivo.

Background: Obesity has been considered as a leading cause of multiple metabolic syndromes, such as type 2 diabetes and hypertension cardiovascular diseases. Jian Pi Tiao Gan Yin (JPTGY), a Chinese herb preparation, is used to treat obesity of liver qi stagnation and spleen deficiency. The mechanism of action of JPTGY in obesity remains unclear. This study evaluated the effect of JPTGY on obesity. Methods: The mechanism of action of JPTGY on obesity was investigated in high-fat diet (HFD)-induced obese mice and palmitic acid-treated 3T3-L1 cells. Lipid droplet accumulation was detected using oil red O staining. Factors associated with lipid accumulation were detected by western blotting. Results: Treatment with JPTGY reduced HFD-induced adiposity and body weight gain. JPTGY increased the levels of brown adipose tissue biomarkers in obese mice and palmitic acid-treated 3T3-L1 cells, including peroxisome proliferator-activated receptor gamma coactivator-1-alpha (PGC-1α) and uncoupling protein-1 (UCP-1). Meanwhile, the protein expression of white adipose tissue biomarkers, such as AGT, primary subtalar arthrodesis (PSTA), and endothelin receptor type A (EDNRA), was decreased in obese mice and palmitic acid-treated 3T3-L1 cells. JPTGY affects browning of 3T3-L1 cells through mechanistic target of rapamycin complex 1 (mTORC1) signaling. JPTGY decreased the expression levels of key adipogenic-specific proteins and lipogenic enzymes, including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), sterol regulatory element binding protein (SREBP), and FAS. Treatment with the mTOR activator MHY reversed JPTGY-mediated protein expression. Conclusions: We concluded that JPTGY relieved obesity phenotypes through mTORC1/SREBP1 signaling in vitro and in vivo. JPTGY may benefit the attenuation of obesity.

Mechanisms of the Jian Pi Tiao Gan Yin in the treatment of simple obesity revealed by network pharmacology.

Background: This study sought to examine the mechanism of the Jian Pi Tiao Gan Yin in the treatment of obesity by network pharmacology. Methods: The active components and corresponding targets of the Jian Pi Tiao Gan Yin were identified using the traditional Chinese medicine systems pharmacology database and analysis platform, and the obesity-related targets were acquired from the Online Mendelian Inheritance in Man database. The drug and disease targets were also identified. Cytoscape software was used to construct the "active component target" network diagram. The protein-protein interaction network was drawn using the Search Tool for the Retrieval of Interacting Genes/Proteins platform, and the Cytoscape MCODE plugin was used to find clusters for the protein cluster analysis. The gene annotation and analysis were performed with the Metascape database via functional databases, such as the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and Autodock and PyMOL were used for the molecular docking. Results: The GO analysis identified 244 target genes of the Jian Pi Tiao Gan Yin, 1,378 targets of obesity, and 123 targets of drug and disease. Additionally, 208 biological process items, 38 molecular function items, and 33 cell component items were also identified. The KEGG pathway analysis identified the hypoxia-inducible factor, forkhead box O, cyclic adenosine monophosphate, and vascular endothelial growth factor signaling pathways. The results of the molecular docking showed that the main active components of the Jian Pi Tiao Gan Yin in the treatment of obesity were quercetin, kaempferol, stigmasterol, luteolin, isorhamnetin, ß-sitosterol, sapogenin, tanshinone, and formononetin, all of which have been proven to bind to core obesity-related proteins, such as AKT1, interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA), tumor necrosis factor (TNF), tumor protein 53 (TP53), prostaglandin-endoperoxide synthase 2 (PTGS2), caspase-3 (CASP3), mitogen-activated protein kinase 1 (MAPK1), JUN, and epidermal growth factor (EGF). Thus, our study revealed the potential mechanism of the Jian Pi Tiao Gan Yin as a multi-component, multi-target, and multi-channel treatment for obesity. These findings lay the foundation for further studies on the mechanism of the Jian Pi Tiao Gan Yin in obesity treatment. Conclusions: The Jian Pi Tiao Gan Yin can be used as a multi-component, multi-target, and multi-channel treatment for obesity.

The relationship between insulin resistance, adiponectin and C-reactive protein and vascular endothelial injury in diabetic patients with coronary heart disease.

Relationship between insulin resistance, adiponectin and C-reactive protein and vascular endothelial injury in diabetic patients with coronary heart disease (CHD) was investigated. Clinical data of 72 patients with diabetes mellitus diagnosed in Weifang People's Hospital (Weifang, China) from October 2015 to January 2017 were retrospectively analyzed. Thirty patients were combined with CHD and 42 patients were not. There were 43 males and 29 females. General information and clinical data including age, sex, duration of diabetes mellitus, biochemical indicators, fasting insulin levels, CRP, insulin resistance index, arterial lesions of coronary angiography and Gensini scores were collected. The levels of FINS, FPG, HOMA-R and CPR were significantly higher, and the level of ADPN was significantly lower in diabetes complicated with CHD group than that without CHD group (P<0.05). Incidence of single coronary artery disease and mild coronary lesion were significantly lower, and incidences of double and triple lesions were significantly higher in diabetes complicated with CHD group than that without CHD group (P<0.05). Gensini score was significantly higher in diabetes complicated with CHD group than that without CHD group (P<0.05); Analysis of the correlation showed that CRP (r=0.422, P=0.001) and insulin resistance index (r=0.828, P=0.001) were positively correlated with Gensini score, while the adiponectin level was negatively correlated with Gensini score (r= -0.719, P<0.001). Logistic regression analysis showed that FINS, ADPN, HOMA-R, CPR, duration of diabetes mellitus and BMI had independently predictive value for diabetes complicated with CHD (P<0.05). Serum adiponectin, insulin resistance and CPR levels are closely related to diabetes mellitus combined with coronary heart disease, and can affect the degree of vascular endothelial injury in coronary heart disease.