Back

Geranylgeranyl pyrophosphate (GGPP) is associated with hepatic lipid accumulation and insulin resistance in MAO by prenylating Perilipin4

Li, C.; Zhao, Y.; Jiang, S.; Nie, H.-Y.; Zhao, M.-F.; Sun, P.; Zhang, J.-Z.; Wang, X.-C.; Tang, Y.-P.; Yuan, X.-W.; Sun, X.-T.; Shan, X.-D.; He, J.; Liu, J.-H.; Bi, Y.; Fang, L.; Han, X.

2023-09-23 pathology
10.1101/2023.09.19.558458 bioRxiv
Show abstract

Metabolically Abnormal Obesity (MAO) is characterized by hepatic steatosis and type 2 diabetes (T2D), in contrast to Metabolically Healthy Obesity (MHO). In this study, we investigated the role of hepatic geranylgeranyl pyrophosphate (GGPP), a metabolite of the mevalonate (MVA) pathway, in regulating the differences in lipid metabolism between MAO and MHO. Our findings revealed that GGPP levels were significantly elevated in individuals with MAO, and deficiency of GGPP in the liver ameliorated the defects associated with MAO. Furthermore, we discovered that the prenylation of the lipid droplet-associated protein Perilipin 4 by GGPP enhances the formation of large lipid droplets, thereby exacerbating hepatic lipid accumulation and insulin resistance. Notably, the inhibitor DGBP, targeting the GGPP synthase Ggpps, effectively attenuated the traits of MAO, offering novel insights into the treatment of this condition.

Matching journals

The top 7 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.