Maternal high-fat diet associated with LPS gestational injection induces hypothalamic inflammation and metabolic disorders in male Wistar rat offspring

Abstract

Maternal high-fat diet (HFD) is linked to obesity and inflammation, predisposing offspring to metabolic and nutritional disorders. Accordingly, elevated blood levels of lipopolysaccharide (LPS) are also related to inflammation and metabolic complications in the offspring. The aim of this study was to evaluate the effects of the association of maternal HFD (gestation and lactation) and the LPS injection (gestation) on metabolic, inflammatory, and redox status parameters in male adolescent offspring. Female pregnant Wistar rats received randomly a standard or an HFD during gestation and lactation. On gestation Days 8, 10, and 12, half of the females in each group were intraperitonially injected with LPS (0.1 mg.kg⁻¹). After weaning, all offspring received a standard diet. The dams and part of the male offspring were evaluated at weaning (Postnatal Day [PND] 21; food intake and inflammatory parameters), while the rest of the male offspring were evaluated during adolescence (PND50; food intake, redox status, and inflammatory parameters). HFD dams showed during gestation a lower weight gain. After lactation, HFD and LPS+HFD dams reported higher fat mass accumulation and increased interleukin-6 (IL-6) blood levels. HFD and LPS+HFD offspring showed at weaning higher levels of fat mass, body weight, and body length, besides an increased in hypothalamic IL-6 levels. Noteworthy, at PND50, the LPS+HFD offspring showed higher energy intake, fat mass, and hypothalamic IL-6 levels, in addition to an increased sucrose preference. Therefore, LPS+HFD offspring presented a worsening in energy metabolism, which was probably due to persistent hypothalamic inflammation, and also have a predisposition for the consumption of sweet foods.