Perinatal leptin effects on hypothalamic brain-derived neurotrophic factor and energy balance-related gene regulation

Area of Science:

• Neuroscience
• Metabolic Regulation
• Developmental Biology

Background:

• Brain-derived neurotrophic factor (BDNF) and leptin are crucial for neurodevelopment and regulating feeding and energy balance.
• Early-life nutrition and hormonal signaling can influence long-term metabolic programming.

Purpose of the Study:

• To investigate the metabolic imprinting effects of leptin supplementation during the suckling period on the brain.
• To examine sex-dependent alterations in gene expression related to energy balance and neurotrophic factors.

Main Methods:

• Physiological leptin supplementation was administered to mouse pups during the suckling phase.
• Analysis of cumulative food intake, energy efficiency, lean mass, and hypothalamic gene expression.
• Investigated key genes in energy balance, insulin/leptin signaling, and the BDNF pathway, including methylation analysis of the Bdnf promoter.

Main Results:

• Leptin-treated mice exhibited reduced food intake, enhanced energy efficiency, and increased lean mass.
• Hypothalamic expression of Bdnf, Ppargc1a, and Fndc5 was upregulated by leptin, particularly in females.
• Leptin influenced energy balance genes and signaling pathways sex-dependently, with notable changes in AMPK, ACC, and STAT3 phosphorylation, and altered Bdnf promoter methylation in females.

Conclusions:

• Leptin supplementation during suckling can sex-dependently imprint hypothalamic gene expression, affecting the Ppargc1a/Fndc5/Bdnf pathway.
• This imprinting is associated with a leaner phenotype, with a more pronounced positive impact observed in females.
• Early-life leptin exposure influences long-term metabolic programming and energy homeostasis via neurotrophic and signaling pathways.