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It is reported that high concentrations of fumarate and succinate can enhance the 3-methylation of histones H3K4 and H3K27 by inhibiting KDM5 histone demethylase (responsible for H3K4 demethylation) and JMJD3 histone demethylase, respectively, which in turn promotes the expression of pro-inflammatory cytokine genes (115, 125, 161, 162)
Moreover, downregulation of GLP-1R level is also found in the glomerular endothelial cells of diabetic mice, which may be due to increased GLP-1R degradation resulted from diabetes-induced PKC2 activation 28
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Lifestyle changes that can contribute to weight loss in midlife include managing stress, prioritizing sleep, eating a balanced diet that focuses on protein and fiber, and getting regular exercise that includes on strength training for muscle retention
Data specific to this study including diagnosis codes and cohort characteristics in aggregated format are included in the manuscript as tables, figures, and supplementary files
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