Advanced search
Start date

Obesity-induced blood-brain-barrier dysfunction during postnatal development

Grant number: 23/05465-3
Support Opportunities:Scholarships abroad - Research
Effective date (Start): October 01, 2023
Effective date (End): September 30, 2024
Field of knowledge:Health Sciences - Nutrition - Malnutrition and Physiological Development
Principal Investigator:Cristiano Mendes da Silva
Grantee:Cristiano Mendes da Silva
Host Investigator: Carol Fuzeti Elias
Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
Research place: University of Michigan, United States  


Puberty is a developmental period of physiologic insulin resistance. Increase in insulin secretion stimulates adipose tissue accrual and typical adult fat distribution. Once established, insulin resistance also allows for increased glucose availability and growth. Leptin and leptin resistance are important players in this equation. Leptin, however, is not only a metabolic or "adipostat" hormone. It is also crucial for brain development. Circulating levels of leptin increase 5 to 10-fold at around 10 days of age in rodents independently of fat mass and decrease to adult levels at around 20 days of age. This postnatal leptin surge is associated with synaptic plasticity, myelination, and neurite outgrowth. In a recent publication, Dr. Elias laboratory analyzed changes in hypothalamic transcripts expression in wild type and obese (Lepob) mice during pubertal transition. Through independent and overlapping analyses of three RNAseq database, they identified genes associated with leptin signaling and early postnatal development. Differentially expressed genes were highly enriched in the extracellular matrix and vasculature. Due to the relevance of blood brain barrier (BBB) for metabolism, Dr. Elias laboratory hypothesize that postnatal leptin surge has a role in hypothalamic vasculogenesis and the establishment of the BBB, both key for the postnatal development of the hypothalamic neuroendocrine function. So in this pilot study, we will use in vivo and in vitro approaches to assess the postnatal development of hypothalamic BBB in nutritional obese (small litter size) and Lepob mice. We will also assess if the postnatal leptin surge is sufficient for the typical development of hypothalamic BBB and energy balance. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
Articles published in other media outlets (0 total):
More itemsLess items

Please report errors in scientific publications list using this form.