EMBO Reports · 22 authors, 10 centres
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The study used a mouse model to show that a nutrient-sensitive SUMO modification of the transcription factor Prox1 in the liver regulates fasting metabolism. Preventing this modification in obese mice lowered systemic cholesterol levels by inducing bile acid detoxification pathways.
This preclinical study used a hepatocyte-selective knock-in mouse model to investigate the role of SUMOylation on transcription factor Prox1 in hepatic metabolism. The authors found that Prox1 SUMOylation is high in the fed state but abolished upon fasting in lean mice. In obese mice, this SUMO switch becomes less sensitive to fasting. Expression of a SUMOylation-deficient Prox1 mutant in obese mice on a high-fat/high-fructose diet led to reduced circulating LDL and HDL cholesterol levels during fasting. This was associated with the induction of genes involved in bile acid detoxification, such as Cyp3a11 and Ugt1a5.
