Leptin Promotes White Adipocyte Browning by Inhibiting the Hh Signaling Pathway

Cells. 2019 Apr 24;8(4):372. doi: 10.3390/cells8040372.

Abstract

Leptin is an important secretory protein that regulates the body's intake and energy consumption, and the functions of the Hh signaling pathway related to white adipocyte browning are controversial. It has been reported that leptin plays a critical role in adipogenesis by regulating the Hh signaling pathway, but whether there is a functional relationship between leptin, the Hh signaling pathway, and adipocyte browning is not clear. In this research, mouse white pre-adipocytes were isolated to explore the influence of the Hh signal pathway and leptin during the process described above. This showed that leptin decreased high fat diet-induced obese mice body weight and inhibited the Hh signaling pathway, which suggested that leptin and the Hh signaling pathway have an important role in obesity. After activation of the Hh signaling pathway, significantly decreased browning fat-relative gene expression levels were recorded, whereas inhibition of the Hh signaling pathway significantly up-regulated the expression of these genes. Similarly, leptin also up-regulated the expression of these genes, and increased mitochondrial DNA content, but decreased the expression of Gli, the key transcription factors of the Hh signaling pathway. In short, the results show that leptin promotes white adipocyte browning through inhibiting the Hh signaling pathway. Overall, these results demonstrate that leptin serves as a potential intervention to decrease obesity by inhibiting the Hh signaling pathway.

Keywords: Hh signaling pathway; adipocyte; browning; leptin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism*
  • Adipocytes, Beige / metabolism
  • Adipocytes, Brown / metabolism
  • Adipocytes, White / metabolism
  • Adipogenesis / genetics
  • Adipose Tissue, Beige / metabolism
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White / metabolism
  • Adiposity
  • Animals
  • Diet, High-Fat
  • Hedgehog Proteins / metabolism*
  • Leptin / metabolism*
  • Leptin / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / genetics
  • Signal Transduction
  • Transcription Factors / genetics

Substances

  • Hedgehog Proteins
  • Leptin
  • Transcription Factors