[The molecular mechanism of fibroblast growth factor 21-inhibited leptin expression in adipocytes]

Area of Science:

• Cell Biology
• Endocrinology
• Molecular Biology

Background:

• Leptin, a key regulator of energy balance, is primarily produced by adipocytes.
• Fibroblast growth factor 21 (FGF21) is an endocrine hormone with diverse metabolic functions.
• The precise molecular mechanisms by which FGF21 influences leptin expression remain incompletely understood.

Purpose of the Study:

• To elucidate the signaling pathways through which FGF21 modulates leptin gene expression in adipocytes.
• To investigate the roles of ERK1/2, AMPK, PI3K, and Akt pathways in FGF21-mediated regulation of leptin.

Main Methods:

• Utilized differentiated 3T3-F442A adipocytes.
• Quantified leptin mRNA levels using fluorescence quantitative RT-PCR.
• Assessed protein phosphorylation in signaling pathways via Western blot analysis.
• Employed specific inhibitors for FGF21 receptor, ERK1/2, AMPK, PI3K, and Akt.

Main Results:

• FGF21 significantly down-regulated leptin mRNA expression in adipocytes.
• FGF21 receptor inhibition abolished FGF21's effect on leptin expression.
• FGF21 increased the phosphorylation of ERK1/2 and AMPK.
• Inhibitors of ERK1/2 and AMPK partially or fully blocked FGF21's inhibitory effect on leptin.
• PI3K and Akt pathway inhibitors did not affect FGF21's regulation of leptin.

Conclusions:

• FGF21 inhibits leptin gene expression in adipocytes.
• The inhibitory action of FGF21 on leptin is mediated through the activation of ERK1/2 and AMPK signaling pathways.
• These findings clarify a crucial molecular mechanism of FGF21 action in adipocytes, relevant to metabolic regulation.