Assessment of modulatory effects and mechanisms of the synthetic fragment of leptin LEP5 in the regulation of hematopoiesis of mice subjected to protein malnutrition

• Grant number: 15/04438-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2015
• Effective date (End): October 31, 2018
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Ricardo Ambrósio Fock
• Grantee: Carolina Carvalho Dias
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Malnutrition is responsible for 55% of child deaths worldwide and is considered the most deadly disease for children under five years of age. The FAO (Food and Agriculture Organization) says that in 2012 there were about 86 million malnourished people worldwide. Protein-energy malnutrition (PEM) is the most prevalent form of malnutrition and is defined by the WHO (World Health Organization) as: "a set of pathological conditions stemming from the lower intake, in varying proportions, protein and calories". It is already known that the (PEM) causes haematological disorders such as anemia and histological changes in the extracellular matrix (ECM) with atrophy of the erythroid compartment, granulo-monocytic and degeneration medular. The ECM also plays an essential role in modulating the response to growth factors, cytokines, modulating biological functions such as proliferation, differentiation, adhesion and migration of hematopoietic cells. The protein hormone called leptin satiety not only plays role in the metabolic regulation of the organism and energy, but also in the reproductive system, the immune response, wound healing, in the vascularization in cardiac function, as in the degenerative processes Alzheimer, in breast cancer and hematopoiesis. Thus, studies related to fragments peptide of leptin (bioactives) have been of great importance, since they are easier to produce and inexpensive. So, in previous studies with fragment LEP5 Ac-[Ser117]-hLEP116-140-NH2, this demonstrated bioactivity, because it increased the amount of hematopoietic stem cells in mice and presented clonogenic capacity when he increased the amount of CFU-GM. Knowing that the immune-hematopoietic system of animals that have PM is impaired, we will study the modulatory effects of the synthetic fragment of leptin, LEP5, as well as evaluate its mechanism of action which has not been elucidated. (AU)