Reducing hepatic PKD activity lowers circulating VLDL cholesterol
Amanda J Genders, Timothy Connor, Shona Morrison, Simon T Bond, Brian G Drew, Peter J Meikle, Kirsten F Howlett, Sean L McGee
Journal of Endocrinology | BIOSCIENTIFICA LTD | Published : 2020
Protein kinase D (PKD) is emerging as an important kinase regulating energy balance and glucose metabolism; however, whether hepatic PKD activity can be targeted to regulate these processes is currently unclear. In this study, hepatic PKD activity was reduced using adeno-associated virus vectors to express a dominant-negative (DN) version of PKD1, which impairs the action of all three PKD isoforms. In chow-fed mice, hepatic DN PKD expression increased whole-body glucose oxidation, but had only mild effects on glucose and insulin tolerance and no effects on glucose homeostasis following fasting and refeeding. However, circulating VLDL cholesterol was reduced under these conditions and was ass..View full abstract
This study was supported by funding from the Centre for Molecular and Medical Research, Deakin University, to S L M.