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Circadian modulation of peripheral insulin sensitivity in malnourished mice submitted to hyperlipidic diet

Grant number: 14/03905-7
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2014
Effective date (End): March 31, 2015
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Everardo Magalhães Carneiro
Grantee:Fernando de Werk Moraes
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Many physiological functions such as sleep-wake cycle, locomotor activity and feeding behavior oscillate in cycles of approximately 24 h or circadian. Mammals are endowed with specialized systems that sense time and interact with the endocrine system resulting in a circadian profile of hormone secretion, especially insulin, enabling a fine temporal control of metabolism. The circadian rhythm originates in hypothalamic cells which comprises the suprachiasmatic nuclei (SCN). Peripheral tissues such as liver, muscle and endocrine pancreas, also have intrinsic circadian rhythmicity, since these tissues regulate the expression of mRNAs related to glucose and lipids metabolism in a periodic fashion. Experimental designs which interfere with the circadian control of metabolism increase the odds for the development of obesity, insulin resistance and dyslipidemia. Proper nutrition during pregnancy and early postnatal life is crucial for the development and maturation of the endocrine system. Epidemiological studies showed a correlation between reduced supply of nutrients, mainly proteins, during the perinatal period with the onset of chronic diseases in adulthood such as obesity and diabetes mellitus type 2 (DM2). Rodents subjected to a low protein diet during gestation displayed lower insulin secretion and increased, but transient sensitivity to this hormone. Recently, our group provided evidence for a disrupted circadian profile of hormone secretion in malnourished mice which showed absence of the oscillatory profile of insulin secretion in response to different stimuli across different time-points within a circadian cycle. These changes were associated with profound changes in the expression pattern of clock genes in pancreatic islets and peripheral tissues. Recent literature suggests that in addition to oscillations in insulin secretion profile, the responsiveness to this hormone also exhibits circadian oscillations. However, the circadian pattern of insulin action on a protein malnutrition mouse model is not known. Therefore, this proposal aims to investigate the glucose tolerance and insulin sensitivity profile along different time-points of a circadian cycle in malnourished mice fed on a high fat diet.