Control of hepatic gluconeogenesis by the promyelocytic leukemia zinc finger protein

Siyu Chen; Jinchun Qian; Xiaoli Shi; Tingting Gao; Tingming Liang; Chang Liu

doi:10.1210/me.2014-1164

Control of hepatic gluconeogenesis by the promyelocytic leukemia zinc finger protein

Mol Endocrinol. 2014 Dec;28(12):1987-98. doi: 10.1210/me.2014-1164.

Authors

Siyu Chen¹, Jinchun Qian, Xiaoli Shi, Tingting Gao, Tingming Liang, Chang Liu

Affiliation

¹ Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences (S.C., J.Q., X.S., T.G., T.L., C.L.), Nanjing Normal University, Nanjing, Jiangsu 210023, China; and State Key Laboratory of Natural Medicines (C.L.), China Pharmaceutical University, Nanjing, Jiangsu 210009, China.

Abstract

The promyelocytic leukemia zinc finger (PLZF) protein is involved in major biological processes including energy metabolism, although its role remains unknown. In this study, we demonstrated that hepatic PLZF expression was induced in fasted or diabetic mice. PLZF promoted gluconeogenic gene expression and hepatic glucose output, leading to hyperglycemia. In contrast, hepatic PLZF knockdown improved glucose homeostasis in db/db mice. Mechanistically, peroxisome proliferator-activated receptor γ coactivator 1α and the glucocorticoid receptor synergistically activated PLZF expression. We conclude that PLZF is a critical regulator of hepatic gluconeogenesis. PLZF manipulation may benefit the treatment of metabolic diseases associated with gluconeogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Cells, Cultured
Chromatin Immunoprecipitation
Gluconeogenesis / genetics
Gluconeogenesis / physiology*
Glucose Tolerance Test
Hyperglycemia / genetics
Hyperglycemia / therapy
Immunoprecipitation
Kruppel-Like Transcription Factors / genetics
Kruppel-Like Transcription Factors / metabolism*
Liver / metabolism*
Male
Mice
Mice, Inbred C57BL
Promyelocytic Leukemia Zinc Finger Protein

Substances

Kruppel-Like Transcription Factors
Promyelocytic Leukemia Zinc Finger Protein
ZBTB16 protein, human

Grants and funding

This work was supported by grants from the National Basic Research Program of China (973 Program) (2012CB947600 and 2013CB911600), the National Natural Science Foundation of China (31422028, 31171137, 31271261, and 31401009), the Program for the Top Young Talents by the Organization Department of the CPC Central Committee, the Science Fund for Distinguished Young Scholars of Jiangsu Province (BK20140041), the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine (Nanjing Medical University), and the Priority Academic Program Development of Jiangsu Higher Education Institutions.