Background: G1, a specific agonist targeting the G protein–coupled receptor 30 (GPR30), has demonstrated significant involvement in combating obesity and regulating glucose homeostasis. Nevertheless, the beneficial effects of G1 treatment have solely been investigated in animal models under normal feeding conditions, leaving its therapeutic potential in high‐fat feeding scenarios unexplored.Material and Methods: To address this gap, our study employed an ovariectomized high‐fat diet mouse model to assess the therapeutic effects of G1 in combating obesity and metabolic dysfunction.Results: The findings revealed that G1 treatment resulted in weight loss, but concurrently led to increased blood glucose levels and insulin resistance. Treatment with G1 resulted in an amplification of fat mobilization and an enhancement of pyruvate carboxylase activity in mice fed a high‐fat diet. Moreover, the combined impact of G1 treatment and a high‐fat diet on pyruvate metabolism, as well as the regulation of crucial gluconeogenesis enzymes such as pyruvate dehydrogenase kinase 4 (PDK4), phosphoenolpyruvate carboxykinase (PEPCK), and glucose transporter 2 (GLUT2), expedites the elevation of blood glucose and the progression of insulin resistance.Conclusions: These findings indicate that G1 treatment is influenced by a high‐fat diet, potentially disrupting glucolipid metabolism and promoting insulin resistance alongside its antiobesity effects. Consequently, further investigation is imperative to thoroughly explore this potential toxic side effect of G1 therapy.

Background: It remains uncertain whether a novel composite indicator, the high sensitivity C‐reactive protein (CRP) (hsCRP)‐to‐body mass index (BMI) ratio (CBR), is associated with unfavourable events in subjects who have undergone drug‐eluting stent (DES) implantation. Therefore, we conducted a prospective cohort study to evaluate the associations between the CBR and adverse outcome occurrences. Methods: From January 2013 to December 2013, a total of 9810 subjects who underwent DES implantation were enrolled in the study. The participants were divided into three groups on the basis of the CBR. We defined the primary endpoint as the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs), and the secondary endpoints included the occurrence of all‐cause death, myocardial infarction(MI), stroke or target vessel revascularization (TVR). Kaplan‒Meier (K‒M) analysis and Cox regression analysis were performed to assess the discrepancy in the risk of adverse outcomes between the different CBR groups. Results: Over an average follow‐up period of 26.7 months, 1022 MACCEs were recorded, which included 122 deaths, 392 MIs, 156 strokes and 461 instances of TVR. The results from the K‒M analysis suggested that the rates of MACCEs and MI increased with increasing tertiles of the CBR. Furthermore, Cox regression analysis demonstrated that there were significant associations between a high CBR and increased MACCE and MI risk. Conclusion: In subjects who underwent DES implantation, a higher CBR was significantly related to increased long‐term MACCE and MI risk.

Background: Previous in vivo and in vitro studies have demonstrated that estrogen receptor agonist G-1 regulates glucose and lipid metabolism. This study focused on the effects of G-1 on cardiometabolic syndrome and anti- obesity under a high fat diet (HFD). Methods: Bilateral ovariectomized female mice were fed an HFD for 6 weeks, and treated them with G-1. A cardiomyocyte insulin resistance model was used to simulate the in vivo environment. The main outcome measures were blood glucose, body weight, and serum insulin levels to assess insulin resistance, while cardiac function and degree of fibrosis were assessed by cardiac ultrasound and pathological observations. We also examined the expression of p-AMPK, p-AKT, and GLUT4 in mice hearts and in vitro models to explore the mechanism by which G-1 regulates insulin signaling. Results: G-1 reduced body weight in mice on an HFD, but simultaneously increased blood glucose and promoted insulin resistance, resulting in myocardial damage. This damage included disordered cardiomyocytes, massive accumulation of glycogen, extensive fibrosis of the heart, and thickening of the front and rear walls of the left ventricle. At the molecular level, G-1 enhances gluconeogenesis and promotes glucose production by increasing the activity of pyruvate carboxylase (PC) while inhibiting GLUT4 translocation via the AMPK/TBC1D1 pathway, thereby limiting glucose uptake. Conclusion: Despite G-1's the potential efficacy in weight reduction, the concomitant induction of insulin resistance and cardiac impairment in conjunction with an HFD raises significant concerns. Therefore, comprehensive studies of its safety profile and effects under specific conditions are essential prior to clinical use.