ObjectiveTo explore the metabolic changes during the differentiation of 3T3-L1 adipocytes caused by the treatment of the transient receptor potential vanilloid 4 (TRPV4)-specific agonist GSK1016790A basing on ultra-performance liquid chromatography-mass spectrometry technology. MethodsMouse 3T3-L1 cells were treated with GSK1016790A at different concentrations (0.1, 1, and 10 μmol/L), and the effect of drugs on cell proliferation was detected by cell counting kit-8 method. A mature adipocyte model was constructed, and GSK1016790A was used to activate TRPV4 channel protein activity and verify the expression levels of TRPV4 and triglycerides. Cell metabolites were collected for metabolomic studies, differential metabolites were screened between groups, and related metabolic pathways were analyzed. Results After GSK1016790A intervened in mature adipocytes, the expression levels of TRPV4 mRNA and triglycerides in cells were significantly upregulated (P<0.05). Metabolomics detection found that GSK1016790A screened a total of 45 differential metabolites such as 2-amino-1,3,4-octadecanetriol, linoleic acid, sphingosine, sphinganine, sn-glycerol-3-phosphate and uridine, mainly involving 13 possible metabolic pathways such as sphingolipid metabolism and biosynthesis of unsaturated fatty acids. Conclusion GSK1016790A may promote adipogenesis in adipocytes by activating TRPV4 channel protein activity, and at the same time participate in regulating metabolic pathways such as the biosynthesis of unsaturated fatty acids pathway and sphingolipid metabolism pathway, affecting lipid metabolism in adipocytes.
Objective To assess the burden of hypertensive nephropathy in China and the world from 1990 to 2021 and predict future trends. Methods Based on the Global Burden of Disease Database 2021, standardized prevalence, standardized mortality and standardized disability adjusted life year (DALY) rates were used to describe the burden of hypertensive nephropathy in China and the world from 1990 to 2021. Estimated annual percentage change (EAPC) and autoregressive integrated moving average model were used to reveal the trend of disease burden. Results From 1990 to 2021, the EAPCs of standardized prevalence, standardized mortality and standardized DALY rates of hypertensive nephropathy in China were −0.61% (−0.73%, −0.50%), −0.77% (−0.85%, −0.69%), and −1.00% (−1.09%, −0.91%), respectively. The global EAPCs for standardized prevalence, standardized mortality, and standardized DALY rates of hypertensive nephropathy were −0.16% (−0.18%, −0.13%), 0.97% (0.91%, 1.03%), and 0.63% (0.58%, 0.67%), respectively. The standardized prevalence rate, standardized mortality rate and standardized DALY rate of hypertensive nephropathy in China all showed a downward trend, and the global standardized prevalence rate also showed a downward trend, while the global standardized mortality rate and standardized DALY rate showed an upward trend, and the indicators of disease burden in China were lower than the global level. The standardized mortality rate and the standardized DALY rate of hypertensive nephropathy were higher in males than in females. With the increase of age, the disease burden indicators of hypertensive nephropathy in China and the world were on the rise, and the age of disease and death were concentrated in the age group over 65 years old. Renal dysfunction and hypertension were important risk factors for death in hypertensive nephropathy patients. It was estimated that from 2022 to 2040, the standardized prevalence rate and mortality rate of hypertensive nephropathy would be on the rise in China and the world, and the standardized DALY rate would be on the rise in the world, while in China it would be on the decline. Conclusions The burden of hypertensive nephropathy is heavy in China and the world from 1990 to 2021, and the control of hypertension and prevention of renal dysfunction should be strengthened. It is estimated that the standardized prevalence and mortality of hypertensive nephropathy will increase in China and the world from 2022 to 2040, and the disease burden will remain heavy.