RESUMO
The high fat (HF) fed mothers may program susceptibility in offspring to chronic diseases and affect subsequent generations. The present study evaluated the liver structure in adulthood, focusing on the F1 and F2 generations. Females C57BL/6 (F0) were fed standard chow (SC) or HF diet (8 weeks) prior to mating and during the gestation and lactation to provide the F1 generation (SC-F1 and HF-F1). All other mothers and offspring fed SC. At 3 months old, F1 females were mated to produce the F2 generation (SC-F2 and HF-F2). The liver was kept in several fragments and prepared for histological analysis or frozen for biochemical and molecular analyzes. The F1 and F2 offspring were studied at 3 months old. HF-F1 had higher body mass (BM) compared to SC-F1 (P= 0.001), but not HF-F2 compared to SC-F2. HF-F1 had glucose intolerance when compared to SC-F1, but not HF-F2 compared to SC-F2. HF-F1 (P= 0.009) and HF-F2 (P= 0.03) showed hyperinsulinemia compared to their counterparts. Both groups HF-F1 and HF-F2 showed more steatosis than the SC counterparts (F1 and F2, P<0.0001). HF-F1 showed increased expression of PPAR-gamma and SREBP1-c compared to SC-F1 (P= 0.01). HF-F2 showed increased PPAR-gamma expression compared to SC-F2 (P= 0.04). In conclusion, HF-fed mother impairs both lipogenesis and beta-oxidation pathways in F1 through upregulation of PPAR-gamma and downregulation of PPAR-alpha. In F2, the only lipogenesis is enhanced, but it causes a disrupted PPAR balance, favoring the hepatic lipid accumulation and impaired metabolism in these animals that were not directly exposed to the maternal HF intake.
Los madres alimentadas con dieta rica en grasas (HF) pueden programar una susceptibilidad al desarrollo de enfermedades crónicas en su descendencia y de este modo afectar a las generaciones posteriores. El presente estudio evaluó la estructura del hígado en la edad adulta, centrándose en las generaciones F1 y F2. Las hembras C57BL/6 (F0) fueron alimentadas con dieta estándar (CS) o dieta HF (8 semanas) antes del apareamiento y durante la gestación y lactancia para producir la generación F1 (CS-F1 y HF-F1). Todas las demás madres y crías fueron alimentadas con CS. A los 3 meses de edad, las hembras F1 fueron apareadas para producir la generación F2 (CS-F2 y HF-F2). El hígado se conservó en varios fragmentos y se preparó, por un lado, para el análisis histológico, y por otro, se lo congeló para realizar análisis bioquímicos y moleculares. La descendencia F1 y F2 se estudió a los 3 meses de edad. HF-F1 tuvo una mayor masa corporal (BM) en comparación con CS-F1 (P= 0,001), pero no el grupo HF-F2 en comparación con CS-F2. HF-F1 tenía intolerancia a la glucosa en comparación con CS-F1, pero no el grupo HF-F2 en comparación con CS-F2. HF-F1 (P= 0,009) y HF-F2 (P= 0,03) mostraron hiperinsulinemia en comparación con sus homólogos. Ambos grupos HF-F1 y HF-F2 mostraron más esteatosis que las contrapartes CS (F1 y F2, P <0,0001). HF-F1 mostró una mayor expresión de PPAR-gamma y SREBP1-c en comparación con el grupo CS-F1 (P= 0,01). HF-F2 mostró aumento de la expresión de PPAR-gamma en comparación con CS-F2 (P= 0,04). En conclusión, la madre alimentada con HF presenta ambas vías afectadas, de lipogénesis y de la beta-oxidación, en la F1 a través de la regulación positiva de PPAR-gamma y con regulación a la baja de los PPAR-alfa. En F2, solo ha mejorado la vía de lipogénesis, pero causa un desbalance de PPAR, lo que favorece la acumulación de lípidos hepáticos y la alteración del metabolismo en estos animales que no estaban directamente expuestos a la ingesta materna de HF.
Assuntos
Animais , Masculino , Feminino , Gravidez , Camundongos , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/patologia , Obesidade/complicações , Animais Recém-Nascidos , Western Blotting , Hiperinsulinismo , Lipogênese , Camundongos Endogâmicos C57BL , Efeitos Tardios da Exposição Pré-NatalRESUMO
OBJECTIVE: The aim of this study was to evaluate the effects of maternal obesity on pancreas structure and carbohydrate metabolism in early adult life, focusing on the F1 and F2 generations after F0 maternal pregestational, gestation, and lactation high-fat diet (HF). METHODS: C57 BL/6 female mice (F0) were fed standard chow (SC) or an HF diet for 8 wk before mating and during the gestation and lactation periods to provide the F1 generation (F1-SC and F1-HF). At 3 mo old, F1 females were mated to produce the F2 generation (F2-SC and F2-HF). The male offspring from all groups were evaluated at 3 mo old. RESULTS: F0-HF and F1-HF dams were overweight before gestation and had a higher body mass gain and energy intake during gestation, although only F0-HF dams presented pregestational hyperglycemia. The F1-HF offspring had higher body mass, energy intake, fasting glucose levels, and were glucose intolerant compared with F1-SC offspring. These parameters were not significantly altered in F2-HF offspring. Both F1-HF and F2-HF offspring showed hyperinsulinemia, hyperleptinemia, decreased adiponectin levels, increased pancreatic mass, and islet volume density with elevated α- and ß-cell mass, hypertrophied islet characterized by an altered distribution of α- and ß-cells and weak pancreatic-duodenal homeobox (Pdx)1 immunoreactivity. CONCLUSIONS: Maternal HF diet consumed during the preconception period and throughout the gestation and lactation periods in mice promotes metabolism and pancreatic programming in F1 and F2 male offspring, implying intergenerational effects.