Objectives: 

Pregnancy is associated with hyperphagia,increased fat mass and multiple neuroendocrine adaptations.Maternal adipose tissue secretes rising amounts of interleukin-6 (IL-6),which acts peripherally modulating metabolic function and centrally increasing energy expenditure and reducing fat mass.This work aimed to clarify the role of IL-6 in the central mechanisms governing dam´s energy homeostasis.

Materials: 

We measured the effects of IL-6 deficiency (IL-6-/-) in mice on food intake,body weight,fat mass and expression of key hypothalamic peptides regulating energy balance by ISH during pregnancy.Adipose tissue and hypothalamic IL-6 and IL-6R expression was assessed by qPCR.

Results: 

Weight gain and total fat content was similar in WT and IL-6-/-mice throughout gestation.Abdominal fat increased in early pregnancy,when lack of IL-6 slightly increased relative food intake and fat accretion by 30%;and decreased in the late phase in WT but not in IL-6-/- mice.Adipose tissue IL-6 expression increased 3-fold during mid and late pregnancy while its hypothalamic content remained unchanged.Early and late pregnancy reduced hypothalamic IL-6 R mRNA levels by 30%.Mid-pregnancy in mice stimulates TRH expression in the hypothalamic paraventricular nucleus (PVN) and lack of IL-6 blunted this effect.Hyperphagia during late pregnancy in mice is accompanied by a 50 % reduced mRNA content of POMC and CRH in the hypothalamic arcuate (ARC) and PVN.IL-6 deficiency during this stage stimulates the expression of NPY and AGRP in the ARC,while restoring POMC mRNA content to virgin values.

Conclusions: 

IL-6 reduced hypothalamic sensitivity favored increased food intake and fat deposition in early pregnancy and also exerts a permissive effect on the development of maternal hyperphagia in late pregnancy.This action of IL-6/IL-6R system induces a differential modulation of NPY/AGRP, POMC and TRH expression which support a role of centrally acting IL-6 in food intake and fat mass regulation during pregnancy.