Overexpression of p53 accelerates puberty in high-fat diet-fed mice through Lin28/let-7 system

Exp Biol Med (Maywood). 2021 Jan;246(1):66-71. doi: 10.1177/1535370220961320. Epub 2020 Sep 30.

Abstract

High-fat intake and subsequent obesity are associated with premature onset of puberty, but the exact neuroendocrine mechanisms are still unclear. The transcriptional factor p53 has been predicted to be a central hub of the gene networks controlling the pubertal onset. Besides, p53 also plays crucial roles in metabolism. Here, we explored p53 in the hypothalami of mice fed a high-fat diet (HFD), which showed an up-regulated expression. Besides, we also revealed that overexpressed p53 may accelerate hypothalamo-pituitary-gonadal (HPG) axis activation partially through the c-Myc/Lin28/let-7 system. These results can deepen our understanding of the interaction between metabolic regulation and puberty onset control, and may shed light on the neuroendocrine mechanisms of obesity-related central precocious puberty.

Keywords: High-fat diet; Lin28/let-7 system; central precocious puberty; obesity; p53; puberty onset.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Diet, High-Fat*
  • Female
  • Hypothalamus / metabolism
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Organ Specificity
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Sexual Maturation*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Lin-28 protein, mouse
  • MicroRNAs
  • RNA-Binding Proteins
  • Tumor Suppressor Protein p53
  • mirnlet7 microRNA, mouse