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.

Highlights

  • IntroductionAdipose tissue is an important endocrine organ; it participates in the activities of the body for physiological regulation by secreting a variety of adipose cytokines [1]

  • Adipose tissue plays an important role in maintaining the body’s energy balance

  • It was found that activation of the Hh signaling pathway inhibited white adipocyte browning, while its inhibition promoted white adipocyte browning

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Summary

Introduction

Adipose tissue is an important endocrine organ; it participates in the activities of the body for physiological regulation by secreting a variety of adipose cytokines [1]. Adipocyte differentiation is regulated by multiple cell signaling pathways. Studies have demonstrated that the Hh signaling pathway plays an important role in muscle [2,3] and adipose tissue [4,5], but how it regulates white adipose tissue browning is still unknown. Choi pointed out that the combination of leptin and Lep-R can promote the activation of the Hh signaling pathway, which promotes the trans-differentiation of hepatic stellate cells (HSCs) into hepatic fibrotic cell-type HSCs (MF-HSCs) [6,7]. Leptin may regulate adipocyte synthesis through the Hh signaling pathway

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