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Effects of high-fat diet on proteins of the inflammatory pathway and from serotonergic system: study in vivo in mice offspring's hippocampus and in vitro in neuroblasts (Neuro-2a cells)

Grant number: 15/08441-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2015
Effective date (End): July 31, 2016
Field of knowledge:Health Sciences - Nutrition
Principal Investigator:Cristiano Mendes da Silva
Grantee:Clarissa Tavares Dias
Home Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil

Abstract

Several evidences suggest that the perinatal environment can be especially important in shaping the results both for the health and for disease in later life. The scientific literature has adopted different nomenclatures to explain the incidence of obesity in adulthood, associating it with some adverse environmental stimuli occurring early in life, such as early exposure to high-fat diet (HFD) or obesogenic diet. Many articles have called this phenomenon of "metabolic or fetal programming" or "phenotypic or developmental plasticity". The nutritional status and/or maternal nutrition during pregnancy and lactation is considered an important inducer of "metabolic programming or phenotypic plasticity" both in animals and in humans. National and international epidemiological data are alarming, showing increased prevalence of obesity and/or overweight, associated with high intake of HFD in women of reproductive age, pregnant and/or lactating. Maternal exposure to HFD imprinting significant risks to the offspring's health that may be manifest in adulthood, resulting in: metabolic syndrome, cardiovascular and neurological disorders. Therefore it is essential to investigate possible effects of maternal HFD on the brain development of fetuses and newborns. Early exposure to maternal HFD can affect morphologically and functionally the central nervous system (CNS) of the offspring, promoting cognitive deficits and delayed neurological development. The consumption of HFD has also induced damage on learning and memory associated with hippocampal inflammation. According to Niculescu and Lupu (2009) mice offspring of mothers fed a HFD during pregnant showed a decrease in neurogenesis and neuronal differentiation in the hippocampus. However, despite recent promising discoveries, still there are a few information about the possible molecular mechanisms involved in hippocampal damage occurred in offspring of obese mothers exposed to HFD during pregnancy and suckling. The developmental plasticity offspring's brain seems be modulated by perinatal maternal diet and "programmed" by inflammatory mechanisms linked to obesity and a HFD, both nutritional situations are independently associated with increased systemic levels of inflammatory mediators. Because of the dual role of these recognized immune molecules (e.g., interleukins [IL] -6, IL-1²) in placental function and brain development, any disturbance of their delicate balance with growth factors or neurotransmitters (e.g., serotonin or 5-hydroxytryptamine, 5-HT) promoted by inflammatory events in early life can permanently change the development trajectory of the fetal brain. In addition, the development of the 5-HT neurotransmitter system, that is behavioral and neurotrophic modulator, has also shown sensitivity to high levels of circulating cytokines. Diverse aspects of brain development, including neuronal migration, synaptogenesis and neurogenesis are modulated by the 5-HT system. The increased adiposity in obesity promotes increase of inflammatory markers, including C-reactive protein, IL-6, IL-1², and tumor necrosis factor-± (TNF- ±). Therefore, investigate the association between maternal HFD during pregnancy and lactation, with proteins of the inflammatory pathway and from 5-HT system seems to have significant role clinical and scientific.