Abstract
Resistin promotes hypothalamic neuroinflammation and insulin resistance through Toll like receptor 4 (TLR4), this hormone is thought to be a link between obesity and insulin-resistance. Indeed, resistin plasma levels are higher in obese and insulin resistant subjects. However, the impact of maternal resistin on the predisposition of offspring to hypothalamic neuroinflammation is unknown. Here, female mice were treated with resistin during gestation/lactation periods, then hypothalamic neuroinflammation was investigated in male offspring at p28 and p90. At p28, resistin increased the expression of inflammation markers (IL6, TNFα and NFκB) and TLR4 in the hypothalamus and decreased both hypothalamic insulin and leptin receptors’ expression. The hypothalamic up-regulation IL6, TNFα and TLR4 was sustained until p90 promoting most likely hypothalamic inflammation. Maternal resistin also increased IL6 and TNFα in the adipose tissue of offspring at p90 associated with a higher body weight gain. In contrast, liver and muscle were not affected. These findings reveal that the augmentation of maternal resistin during gestation and lactation promotes hypothalamic and adipose tissue inflammation of offspring as evidenced by sustained increase of inflammation markers from weaning to adulthood. Thus, maternal resistin programs offspring hypothalamic and adipose tissue inflammation predisposing then offspring to body weight gain.
Highlights
The low-grade inflammation in obese, insulin-resistant or type-2 diabetes subjects is an important issue in developmental programming of inflammation and its long-term consequences on offspring [1, 2]
In the present study, we aim to investigate whether maternal resistin has long-term effects on the predisposition of offspring to develop inflammation and metabolic disorders when subjected to HFD, with a special focus on hypothalamic neuroinflammation, termed as perinatal programmed hypothalamic inflammation
Maternal obesity is associated with metabolic inflammation attributed to increased adipose tissue and circulating proinflammatory cytokine levels [1, 27]
Summary
The low-grade inflammation in obese, insulin-resistant or type-2 diabetes subjects is an important issue in developmental programming of inflammation and its long-term consequences on offspring [1, 2]. Hypercaloric maternal diet programs inflammation in offspring tissues [3,4,5,6]. Accumulated evidences suggest that changes of inflammatory markers in early life could have a strong impact on the prevalence of metabolic and cardiovascular diseases [7,8,9]. It has been suggested that offspring inflammation is promoted by LPS-induced maternal inflammation. This treatment led to strong changes in offspring immune system.
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