Kaempferol is a dietary flavanol that regulates cellular lipid and glucose metabolism. Its mechanism of action in preventing hepatic steatosis and obesity-related disorders has yet to be clarified. The purpose of this research was to examine kaempferol’s antiobesity effects in high-fat diet- (HFD-) fed mice and to investigate its impact on their gut microbiota. Using a completely randomized design, 30 mice were equally assigned to a control group, receiving a low-fat diet, an HFD group, receiving a high-fat diet, and an HFD+kaempferol group, receiving a high-fat diet and kaempferol doses of 200 mg/kg in the diet. After eight weeks, the HFD mice displayed substantial body and liver weight gain and high blood glucose and serum cholesterol levels. However, treatment with kaempferol moderated body and liver weight gain and elevation of blood glucose and serum cholesterol and triglyceride levels. Examination of 16S ribosomal RNA showed that HFD mice exhibited decreased microbial diversity, but kaempferol treatment maintained it to nearly the same levels as those in the control group. In conclusion, kaempferol can protect against obesity and insulin resistance in mice on a high-fat diet, partly through regulating their gut microbiota and moderating the decrease in insulin resistance.

Objectives Metabolic syndrome (MS) is the concurrence of at least three of five medical conditions: obesity, high blood pressure, insulin resistance, high serum triglyceride (TG) and low serum high-density lipoprotein levels. While fibrates are used to treat disorders other than the lowering serum TG, the mechanism by which fibrates decrease MS has not been established. Methods In this study, wild-type and Ppara-null mice fed a medium fat diet (MFD) were administered gemfibrozil and fenofibrate for three months, to explore the effect and action mechanism. Key findings In Ppara-null mice, MFD treatment increased body weight, adipose tissue, serum TG, and impared glucose tolerance. These phenotypes were attenuated in two groups treated with gemfibrozil and fenofibrate. The STAT3 pathway was activated in adipose and hepatic tissues in positive control, and inhibited in groups treated with gemfibrozil and fenofibrate. The above phenotypes and inflammation were not observed in any wild-type group. In 3T3-L1 adipogenic stem cells treated with high-glucose, STAT3 knockdown greatly decreased the number of lipid droplets. Conclusions Low dose of clinical fibrates was effective against MS development independent of PPARα, and this action was mediated by STAT3 signaling inhibition in adipose tissue, and to a lesser extent in hepatic tissues.

Background The interleukin (IL)‐36 cytokines include IL‐36α, IL‐36β, IL‐36γ, and IL‐36Ra. Little was known about their roles in type 2 diabetes mellitus (T2DM). Methods The study included 40 T2DM patients and 42 healthy control subjects. The anthropometric and biochemical measurements were performed using automatic biochemical analyzer, high‐performance liquid chromatography, and electrochemiluminescence immunoassay. Circulating IL‐36α, IL‐36γ, IL‐36Ra, and IL‐17 levels were determined by enzyme‐linked immunosorbent assay. Results Serum IL‐36α, IL‐36γ, and IL‐17 levels in T2DM patients were significantly higher than those in controls, whereas serum IL‐36Ra levels in T2DM patients were lower. Correlation analysis showed that serum IL‐36α was positively correlated with high sensitivity C‐reactive protein. Serum IL‐36α was negatively correlated with IL‐36Ra. Serum IL‐17 was negatively correlated with low‐density lipoprotein cholesterol. Conclusions This study demonstrated that T2DM patients displayed increased IL‐36α and IL‐36γ expression and decreased IL‐36Ra expression. Moreover, the inflammatory cytokine levels were directly proportional to the inflammation and blood lipid levels. Our results suggest that IL‐36 cytokines may be a new target for the diagnosis or treatment of T2DM.

<p><b>Abstract:</b><b></b></p><p><b><i>Objective:</i></b> To explore the target of anti-knee osteoarthritis (KOA) in the effective chemical compounds of piper longum L based on network pharmacological methods.<b></b></p><p><b><i>Methods</i></b>: The active chemical compounds of piper longum L were collected employing database retrieval on TCMSP, TCM-PTD, and literature mining. The Swiss Target Prediction service predicts the targets of active chemical compounds, and at the same time, the targets of the drugs treating knee osteoarthritis were collected by retrieving the OMIM and CTD databases. The targets were subjected to an alignment analysis to screen out piperine and we simulated the binding sites in vivo of compounds and proteins via AutoDock. After that, the rat models of knee osteoarthritis were established. The rats in model groups were given piperine treatment. The verification of the anti-KOA target PPARG and MAPK1 was done by Western blot and co-immunoprecipitation.</p><p><b><i>Results</i></b><i>: </i>Nine active ingredients were predicted. According to Lipinski's rule, piperine was speculated as a possible active ingredient. According to the possible targets of piperine and the KOA's possible targets, three co-targets of them were confirmed, PPARG and MAPK1 were related to knee osteoarthritis (KOA). Molecular docking results show that piperine can hinder the binding of PPARG protein ARG-212 and GLN-420 amino-acid residues to each other. After 20 weeks of piperine treating, Western blot found that piperine can significantly increase the expression level of PPARG and reduce the expression level of MAPK1 in model rats. The endogenous interaction between PPARG and MAPK1 was verified by co-immunoprecipitation.</p><p><b><i>Conclusion</i></b><i>:</i> Piper longum L can regulate the progression of knee osteoarthritis (KOA) by its active ingredient piperine，can affect the expression of PPARG and MAPK1 proteins, and PPARG and MAPK1 proteins have endogenous interactions.</p>

Short comm.of fasting insulin (FINS) was determined by electrochemiluminescence immunoassay. IR was estimated using homeostasis model assessment of insulin resistance (HOMA-IR): HOMA-IR = FINS (μU/mL) × FBG (mmol/L)/22.5. Enzyme-linked immunosorbent assays (ELISA) were used to determine the serum levels of IL-38 and interleukin 17 (IL-17) of the subjects. All statistical analyses were performed using GraphPad Prism 9.0 software. Data were presented as mean ± SD. The unpaired t test was used for comparative analysis of the 2 groups. Correlations between IL-38 and variables were assessed by Pearson correlation analysis. p < 0.05 was considered statistically significant. ResultsAs shown in Supplementary File -Table S1, there were no statistically differences in gender distribution, age, height, and DBP between the T2DM patients and the healthy control subjects (p > 0.05). The BMI, SBP, and body weight of the T2DM patients were higher than those of the control subjects, with a statistically significant difference (p < 0.05). The levels of TC, TG, HbA 1c , LDL, FBG, FINS, HOMA-IR, and CRP of the T2DM patients were significantly higher than those of the control subjects (p < 0.05). The HDL was not statistically different between the 2 groups (p > 0.05) (Supplementary File-Tab. S2).As shown in Figure 1, we detected serum IL-38 and IL-17 levels by ELISA. The serum IL-38 levels in T2DM patients were significantly lower than those in the control group (p < 0.001, Fig. 1A). Conversely, serum