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Effects of high-fat diet on gestation and lactation on the central and peripheral metabolism of serotonin: study of the hypothalamus and visceral adipose tissue in mothers and offspring

Grant number: 18/00449-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2018
Effective date (End): August 31, 2019
Field of knowledge:Health Sciences - Nutrition - Malnutrition and Physiological Development
Principal Investigator:Cristiano Mendes da Silva
Grantee:Maria Laura Monteiro da Luz Camargo
Home Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil


Different nomenclatures have been use to explain the incidence of obesity in later life associated with possible adverse environmental stimuli occurred in early life, such as early exposure to obesogenic diets (e.g. High-Fat Diets) during pregnancy and/or suckling. Many authors have named this phenomenon of "metabolic or fetal programming" (Barker, 2002; Armitage et al., 2005), or "phenotypic or developmental plasticity" (Gluckman et al., 2007-2008; Hanson et al., 2011; Hanson and Gluckman, 2011). In this context, nutritional status and/or maternal nutrition during gestation and lactation is considered an important inducer of "metabolic programming or phenotypic plasticity" in both animals and humans (Howie et al., 2009). National and international epidemiological findings are alarming, because its show increase in the prevalence of obesity and/or overweight associated with HFD intake in women of reproductive age, pregnant and / or lactating women (Kim et al., 2007, WHO, 2011, Vigitel, 2011; Dong et al., 2012). Maternal HFD may damage to the health of offspring, resulting in adulthood: metabolic syndrome (Ashino et al, 2012; Melo et al, 2014), cardiovascular diseases (Poston, 2012) and neurological disorders, including affecting neurotransmitter systems, such as the serotonergic (Peleg-Raibstein et al, 2012; Giriko et al, 2013; Melo et al, 2014; Mendes-da-Silva et al., 2014 Sasaki et al, 2014). The serotonin (5-hydroxytryptamine or 5-HT) is a biogenic amine that resides in non-neuronal (peripheral) and neuronal tissues. The key enzyme responsible for serotonin synthesis is tryptophan hydroxylase (TPH), found as TPH1 in peripheral tissues, such as the gastrointestinal tract and adipose tissue; and as TPH2 in neural tissues, mainly in the Central Nervous System (CNS), in structures such as the brainstem, hippocampus and hypothalamus (Stephen, Abraham, 2017).In central nervous system (CNS) the 5-HT represents 5% of all produced, that has several functions, among these to modulation of the appetite (Crane et al., 2014). On the other hand, the peripheral serotonin represents 95% of endogenous production and it is present in the blood, gastrointestinal tract, pancreas and adipose tissue (Stephen, Abraham, 2017). Recent findings suggest that increased peripheral serotonin and polymorphisms in TPH1 are associated with obesity (Crane et al., 2014).In a study by Stephen and Abraham (2017), analyzing the effect of a high-fat simple carbohydrate diet (HFSC) on C57BL / 6J mice upon the serotonin metabolic pathway in the central system - hypothalamus and corpus striatum - and in the peripheral systems - in plasma and urine - it was found that both the hypothalamus and corpus striatum participate in food intake control and satiety. The hypothalamus is the major region of the brain for regulation of food intake and energy balance in mammals. Under physiological conditions, a variety of peripheral signals regulate appetite and adjusts energy intake to match energy consumption requirements. Evidence suggests that hypothalamic "inflammatory" activation as a result of a high-fat diet (HFD) and obesity can disrupt anorexigenic and thermogenic signals and promote abnormal control of body weight (Manousopoulou et al., 2016). Hypothalamic serotonin has been implicated in satiety and in the absorption of nutrientes, being associated with the ingestion of carbohydrates and fats. From the evidence presented, the objective of this study is to evaluate the effect of the hyperlipidic diet during pregnancy and lactation on the serotonergic system in the adipose tissue (offspring) and hypothalamus (mothers and offspring).