Bioactive food compounds, epigenetics and chronic disease prevention: Focus on early-life interventions with polyphenols.

Consumption of bioactive compounds such as polyphenols, isothiocyanates, sulfur-containing compounds and terpenoids, found in fruits and vegetables, is associated with prevention of chronic disease. These bioactive food compounds elicit their protective effects through complex mechanisms at the cellular and molecular, including epigenetic levels. According to the Developmental Origins of Health and Disease (DOHaD) paradigm, in utero exposure to stressors such as malnutrition through maternal diet would impair fetal development and epigenetically program increased risk of metabolic diseases and some cancers in adult life. In addition, a role for fathers´ diet during preconception on their offspring health and chronic disease susceptibility has also emerged. This highlights early life as a promising window of opportunity for starting dietary interventions focusing on preventing chronic diseases. However, knowledge on the potential beneficial impact of early life exposure to bioactive food compounds is limited. Among the studies that have investigated bioactive food compounds in the context of DOHaD, most have focused on the impact of dietary polyphenols. Thus, in this review we discuss experimental evidence supporting a role for the dietary polyphenols resveratrol, genistein, epigallocatechin-3-gallate and anthocyanins in chronic disease prevention considering a perspective from early-life interventions through maternal and paternal diets and focusing on epigenetics as a potential underlying mechanism.

Hypercaloric Diet-Induced Obesity and Obesity-Related Metabolic Disorders in Experimental Models.

Overnutrition and obesity have developed into a major public health problem across different parts of the world. Epidemiological studies have shown that excessive intake of dietary components, such as fatty acids and/or sugars, can promote obesity. In this context, the use of dietary intervention in animal models that respond to a diet similar to humans is useful to understand this preventable, multifactorial disease. The aim of this chapter is to aid researchers in choosing specific nutritional interventions and animal strains to induce obesity and obesity-related morbidities in experimental models.

Influence of paternal consumption of a high-fat/high-sugar diet and/or orange juice during preconception on C57BL/6 female mice offspring breast cancer risk / Influência do consumo paterno de uma dieta hiperlipídica/hiperglicídica e/ou suco de laranja durante a preconcepção no risco de câncer de mama na prole feminina de camundongos C57BL/6

Breast cancer is the most frequent cancer in women worldwide. Paternal consumption of a highfat diet has been shown to program breast cancer risk in female offspring. Orange juice is widely consumed and is known for its content of bioactive compounds that may have a role in regulating epigenetic processes. Therefore, the aim of the present study was to evaluate the effects of paternal obesity and orange juice consumption on female offspring susceptibility to chemically-induced breast carcinogenesis. Three-week-old C57BL/6 male mice were distributed in control (CO), control-orange juice (CJ), obese (OB) and obese-orange juice (OJ) groups, fed either a standard chow or a high-fat/high-sugar diet (45% lard-based diet supplemented with sweetened condensed milk), with water or orange juice, for 11 weeks before mating. Female offspring were weaned onto standard chow until 7 weeks of age and then were initiated with 7,12-dimethyl-benzo[a]anthracene to induce mammary tumors. CJ female offspring presented higher multiplicity of mammary tumors (p≤0.05) compared to CO offspring. Female offspring from OB group showed higher tumor latency (p≤0.05), lower tumor incidence (p≤0.05), higher multiplicity of tumors (p≤0.05), lower cell proliferation (Ki67) in the mammary ducts (p≤0.05) and lower global levels of H3K27me3 in the mammary gland (p≤0.05) when compared to CO offspring. No differences (p≥0,05) were observed between OB and OJ female offspring regarding these parameters. Consumption of orange juice by non-obese fathers during preconception increased susceptibility of female offspring to mammary carcinogenesis. Although paternal consumption of a high-fat/high-sugar diet during preconception decreased incidence and increased latency of tumors, the multiplicity of lesions increased. In addition, the data indicates that the response to orange juice consumption depends of the paternal metabolic context

O câncer de mama é o mais frequente entre as mulheres em todo o mundo. Foi demonstrado que o consumo paterno de uma dieta hiperlipídica aumenta o risco de câncer de mama nas filhas. O suco de laranja é amplamente consumido e é conhecido pelo seu conteúdo de compostos bioativos que podem ter um papel na regulação dos processos epigenéticos. Portanto, o objetivo do presente estudo foi avaliar os efeitos da obesidade paterna e do consumo de suco de laranja na suscetibilidade da prole feminina à carcinogênese mamária quimicamente induzida. Camundongos C57BL/6 machos com três semanas de idade foram distribuídos nos grupos controle (CO), controle de suco de laranja (CJ), obeso (OB) e obeso suco de laranja (OJ), alimentados com ração controle ou com ração hiperlipídica e hiperglicídica (45% das calorias proveniente de lipídeos, a base de banha de porco) suplementada com leite condensado, com água ou suco de laranja, durante 11 semanas antes do acasalamento. A prole feminina foi desmamada e recebeu ração controle até 7 semanas de idade e, então, foi iniciada com 7,12- dimetil-benzo[a]antraceno para induzir tumores mamários. A prole feminina CJ apresentou maior multiplicidade de tumores mamários (p≤0.05) em relação a prole feminina CO. A prole feminina OB apresentou maior latência tumoral (p≤0.05), menor incidência tumoral (p≤0.05), maior multiplicidade de tumores (p≤0.05), menor proliferação celular (Ki67) nos ductos mamários (p≤0.05) e menores níveis globais de H3K27me3 na glândula mamária (p≤0.05), quando comparada a prole feminina CO. Não foram observadas diferenças (p≥0,05) entre a prole feminina do OB e OJ em relação a esses parâmetros. O consumo de suco de laranja por pais não obesos durante o período pré-concepcional aumentou a susceptibilidade da prole feminina à carcinogênese mamária. Embora o consumo paterno de uma dieta hiperlipídica e hiperglicídica durante a preconcepção tenha diminuído a incidência e aumentado a latência, a multiplicidade dos tumores mamários aumentou. Ainda, os resultados indicam que a resposta ao consumo de suco de laranja depende do contexto metabólico paterno