The establishment of the Russian Academy of Sciences, Institute of cytology and genetics, Novosibirsk, Russia, firstname.lastname@example.org
Now obesity and obesity-related pathologies, such as type 2 diabetes have taken the character of world-wide epidemic. The obesity development is known to be depended on interaction of genetic and environmental factors. Food intake is known to changed during the individual development. Pregnancy and lactation are characterized by increased and emotional stress – decreased appetite. The aim of the study was to investigate whether physiological states with relatively high and low food intake will affect the development of genetically-determined hyperphagia and obesity. C57Bl/6J mice carrying lethal yellow mutation at the Agouti locus (Ay/a mice) predisposed to the obesity and diabetes 2 development were used.The Ay mutation reduces melanocortin (MC) system activity which controls energy balance under the rest conditions. Mice of standard C57Bl/6J genotype (a/a mice) served as metabolic control. Repeating emotional stress (0,5h restraint х 3 times a week x 5 weeks) hampered development of obesity and 2 type diabetes in the Ay/a mice. Acute (1 h restraint) emotional stresses inhibited feeding and decreased plasma insulin levels only in the Ay/a mice. Anorexia in stressed Ay/a mice was independent of pathways involving hypothalamic orexigenic neuropeptide AgRP, NPY and HPA axis and might be associated with increased anorexic signal through corticotrophin-releasing factor 2 receptor (CRFR2) in the hypothalamus. Pregnancy and lactation eliminated hereditary hyperphagia, delayed obesity and diabetes development in the Ay/a mice. Lactation induced hyperphagia was independent on the pathways involving hypothalamic orexigenic neuropeptide AgRP, NPY. So, pregnancy and lactation (high food intake) similar to emotional stress (low food intake) prevented the development of genetically determined obesity and improved glucose metabolism in the Ay/a mice. One can assume that MC system, disturbed by the Ay mutation does not play a leading role in the feeding regulation during lactation and emotional stress. Other hypothalamic systems help to keep appétit and consequently glucose metabolism on the new levels appropriated to new physiological needs. These adaptations masked the genetically determined hyperphagia caused by the disturbance in the MC signaling, hampered obesity development and improved glucose metabolism in Ay/a mice.
The study was supported by the RFBR 09-04-00447, 10-04-00331, 11-04-01956.