Pregnancy is a hyper-metabolic state with a great increase in maternal body fat and weight, and it is associated with numerous neuro-endocrine changes. During gestation, there is no increase in energy efficiency, and the energy balance becomes positive at this stage, primarily because of a marked increase in food intake, which is necessary to prevent the depletion of maternal energystores. Interleukin (IL-6) is a multifunctional immune-modulating cytokine that has been suggested to have important functions in glucose and lipid metabolism. IL-6 is secreted from adipose tissue to the circulation, and its expression is positively correlated with BMI and total fat tissue. IL-6 deficient (IL-6-/-) mice develop obesity, which could partly be reversed by IL-6 replacement, suggesting a role for IL-6 in long-term regulation of adipose tissue mass. Furthemore, intracerebroventricular (ICV) injections of a low dose of IL-6 decreased food intake and increased energy expenditure in rats, suggesting a central site of action of IL-6. By using theIL-6 deficient mice as a tool, we will carefully analyse the long-term effects of lack IL-6 on bodyweight, fat mass distribution, food intake and metabolism during pregnancy and lactation.
Several hypothalamic neuropeptides have been identified as possible regulators of food intake and metabolism. These neuropeptides have been reported to display either orexigenic (NPY, AgRP,MCH and orexins) or anorexigenic (POMC, CART, and CRH) functions and to be inhibited or stimulated by leptin levels, respectively. Nutritional status can alter the expression of these appetite-regulating peptides, but most studies have investigated acute changes with fasting, and the effects of a long-term state of hyperphagia as gestation remains to be fully defined. During this project we will also attempt to identify at the level of the hypothalamus the site and possible mechanism of action of endogenous IL-6 on food intake.
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