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...connections

To regulate energy balance – the balance between energy consumed as food and energy expenditure – the brain integrates signals from the periphery (gut, pancreas, fat tissue) and transmits information via a network of connections between hypothalamic centres and other more widely distributed brain centres. These projections between different brain structures are formed early in life, to a timetable that varies between mammalian species, relative to normal term birth. In the rodent, for example, hypothalamic projections are not fully developed until the third week of postnatal life, whereas in humans and non-human primates, the equivalent circuits are formed in utero during the third trimester of pregnancy. This developmental timing sets the window within which maternal or post-natal nutrition is likely to influence the density and direction of intra-hypothalamic projections and wider brain circuitry. There is now strong evidence from the study of developing hypothalamic systems in wild-type and mutant rodents that peripheral hormones, in particular the fat tissue hormone, leptin, can directly influence the development of neuronal systems and their interconnectivity. In the ob/ob mouse, in the absence of leptin, projections within the hypothalamus fail to develop normally, with reduced nerve fibre density through into adult life. Leptin is able to promote the development of these projections, increasing density and length. These findings suggest that abnormally low or high concentrations of leptin in the human maternal circulation during late pregnancy, such as could result from malnutrition or obesity, respectively, might influence the development of brain connections in the developing foetus. The impact of such changes on functions such as hunger, satiety, precision of energy balance, diet preference etc remains to be determined.