Perfil nutricional, metabólico e parâmetros inflamatórios hipotalâmicos em ratos adultos submetidos à desnutrição proteica intrauterina e recuperados após o nascimento

Abstract

Epidemiological studies have demonstrated a relationship between low birth weight and obesity and type 2 diabetes mellitus in adult life. Body weight, food intake and metabolism are regulated by the hypothalamus that processes central and peripheral signals. Increased hypothalamic inflammation could be factor contributing to susceptibility to obesity and glucose intolerance/diabetes in rats exposed to early malnutrition. We evaluated whether protein restriction in fetal life alter food intake and glucose homeostasis in adulthood by interference in the insulin signal transduction in the hypothalamus and peripheral tissues through pro-inflammatory mechanisms. Rats were divided into three groups: a control group (C) consisting of rats born to and suckled by dams fed a control diet during pregnancy, lactation and after weaning; a recovered group (R) consisting of the offspring of dams fed the low protein diet during pregnancy but fed the control diet during lactation and after weaning; and an low protein (LP) group consisting of the offspring of dams fed a LP diet during pregnancy, lactation and after weaning, all experimental procedures involving rats were approved by the ethics committee at the Federal University of Mato Grosso (protocol n° 23108.051511/10- 0).After 120 d old rats were evaluated nutritional and biochemical parameters; gene expression involved in hypothalamus inflammatory pathway, as well as, AKT signaling in different tissues. Serum albumin was diminished in LP in relation to R and C rats. The relative food intake was greater in LP and R rats than C rats (LP: 48.4±2.4; R:39.2±1.6; C:33.7±0.8)The liver glycogen content was similar in R and LP (R: 0.127±0.023; LP:0.158±0.014) rats and both showed greater liver glycogen concentration than the C group (C: 0.082±0.002). Both R and LP rats, showed diminished serum leptin concentrations than C rats (R:3.22±0.28; LP: 2.96±0.16; C: 4.03±0.05). PCR array in hypothalamus showed that, 52 inflammatory genes were up-regulated in R and 59 down- regulated in LP group compared to C group. TNFα expression was high in R group, whereas ILβ did not differ among three groups. Hypothalamus of LP showed greater NPY mRNA expression than of C rats. The R group showed higher POMC mRNA expression in relation to both LP and C groups. AKT phosphorylation in the hypothalamus and liver were similar in R and C rats and higher thanin LP. In muscle, AKT phosphorylation was higher in R and LP than the C rats. Mean total areas under the ∆G were similar in R and C rats and higher thanin LP rats. The HOMA-IR index was decreased in R and C compared to the LP group. In contrast, the Kitt in R was similar from that in C, and both lower than in LP rats. Thus, nutritional recovery did not alter glucose homeostasis, but produced middle hyperphagia possibly due to increased anorexigenic neuropeptide expression that counteracted the hypothalamic inflammatory process. In long term protein deprived rats, hyperphagia probably resulted from increased orexigenic neuropeptide expression and glucose homeostasis was maintained, at least in part, at the expense of increased muscle insulin sensitivity.