Sanye Tablet Ameliorates Insulin Resistance and Dysregulated Lipid Metabolism in High-Fat Diet-Induced Obese Mice

Abstract

Sanye Tablet (SYT) is a patent prescription widely used in treating T2D and pre-diabetes, especially T2D comorbid with hypertriglyceridemia, for many years in China. However, the underlying mechanism that accounts for the anti-diabetic potential of SYT by regulating lipid-related intermediates remains to be elucidated. This study aimed to investigate the mechanism of SYT on lipid metabolism and insulin sensitivity in high-fat diet (HFD)-induced obese mice by means of combining lipidomics and proteomics. The obese mice models were developed via HFD feeding for 20 consecutive weeks. Mice in the treatment group were given metformin and SYT respectively, and the effects of SYT on body weight, blood glucose, insulin sensitivity, fat accumulation in the organs, and pathological changes in the liver were monitored. Lipid metabolism was examined by lipidomics. Further determination of signaling pathways was detected by proteomics. The biological contributions of the compounds detected in SYT’s chemical fingerprint were predicted by network pharmacology. SYT treatment reduced body weight, inhibited viscera and hepatic steatosis lipid accumulation, and prevented insulin resistance. Furthermore, it was found that circulatory inflammatory cytokines were reduced by SYT treatment. In addition, lipidomics analysis indicated that SYT targets lipid intermediates, including diacylglycerol (DAG) and Ceramide (Cer). Mechanistically, SYT positively affected these lipid intermediates by suppressing liver lipogenesis via downregulation of SREBP1/ACC and the JAK/STAT signaling pathway. Our results predicted that astragalin and rosmarinic acid might regulate the JAK-STAT pathway by targeting PIM2 and STAT1, respectively, while paeoniflorin and rosmarinic acid were likely to regulate inflammatory responses by targeting TNFα, IL-6, and IL-4 during T2D. Overall, our study provides supportive evidence for the mechanism of SYT’s therapeutic effect on dysregulated lipid metabolism in diabesity.

Endothelial ADAM17 Expression in the Progression of Kidney Injury in an Obese Mouse Model of Pre-Diabetes

“…As depicted in Table 1 , fasting blood glucose levels were higher in all obese mice as compared to SD-fed mice, but the values did not exceed 250 mg/dL. Therefore, HFD-mice were considered prediabetic, as described before [ 22 ]. Urinary albumin was calculated by the albumin-to-creatinine ratio (ACR).…”

Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes

“…As depicted in Table 1 , fasting blood glucose levels were higher in control mice fed an HFD as compared to mice fed an SD, but without exceeding 250 mg/dL. Therefore, HFD mice were considered pre-diabetic, as described before [ 13 ]. Interestingly, HFD mice with proximal tubular Adam17 deletion showed similar fasting blood glucose levels as compared to SD mice.…”

Sex-specific transcriptional rewiring in the brain of Alzheimer’s disease patients

“…Consistent with the pathway analysis, some transcription factors are associated with insulin signaling. For example, CREB3, STAT1, and STAT3 are important regulators of glucose and lipid metabolism in models of high-fat diet and obesity ( Bone et al, 2020 ; Yao et al, 2021 ; Kiran et al, 2022 ; Opazo-Rios et al, 2022 ; Smith et al, 2022 ). In the context of neurodegeneration, CREB3 and STAT3 are involved in neuroprotective mechanisms.…”