Mães obesas, filhotes obesos: estudo experimental

Abstract

Maternal obesity is increasing in prevalence, reflecting in gender-related deleterious effects in offspring in adulthood. This work aimed to verify the hypothesis that maternal obesity causes metabolic abnormalities, alterations in structure of the liver and adipose tissue and pro-inflammatory profile changes in adult offspring of males and females. Pregnant C57BL / 6 mice received standard chow (SC; 17% energy from fat) or high fat diet (HF; 49% energy from fat) for eight weeks pre-pregnancy until lactation. After weaning, offspring were divided into groups, according to diet of dams: SCM (male), SCF (female), HFM (male) and HFF (female). The metabolic characteristics were evaluated by the curve of body mass (BM), fasting glucose, area under the curve after oral glucose tolerance test, hepatic triglyceride and estimation of hepatic steatosis, analysis of plasma insulin, total cholesterol (TC), triglycerides (TG), and adipokines; distribution and morphological analysis of adipose tissue and pro-inflammatory state of the offspring. Differences between groups were analyzed by unpaired t test (data between progenitor and offspring groups in pairs), one-way ANOVA with Tukey post-test (for offspring) and two-way ANOVA to determine the effect of maternal diet and gender. The level of significance adopted was P ≤ 0.05. Dams fed HF diet had greater BM (+20%), increased blood glucose (+22%) and glucose intolerance than SC dams. In the offspring, BM was greater in HF offspring than SC offspring, both genders, since the fourth week of age. At 12th week, BM was 20% greater in HF male and 30% greater in HF female than in their SC counterparts (P<0.0001, both genders). Glucose intolerance was observed in both male and female HF offspring compared with their relative SC ones (+20%; P<0.05). HF offspring showed hepatomegaly with increased liver triglyceride accumulation, which resulted in a greater percentage of steatosis in male (27%) and in female HF (25%). HF offspring had 20% greater adiposity and higher levels of TC and TG than SC counterparts. Leptin and insulin plasma levels were higher and adiponectin level was lower in HF male than in SC male. Adipocytes were much bigger in HF offspring than in SC offspring. TNF-alpha, IL-6 and leptin protein were significantly more expressed in HF than in SC offspring, but the contrary happened with adiponectin protein expression. HF diet administrated to mice females prior and during gestation and lactation periods leads to maternal obesity that has consequences in the offspring, such as adipose tissue remodeling together with biochemical and metabolic changes of adipocytes, intensifying the pro-inflammatory state in both genders offspring in adulthood.