Prenatal stress modifies protein expression in the liver to affect metabolic status Sheba M.J. MohanKumar1, Priya Balasubramanian1, Simon L Abdallah2, Sonia M. Najjar2, P.S. MohanKumar1. Neuroendocrine Research Laboratory College of Veterinary Medicine Michigan State University Center for Diabetes Education and Research University of Toledo OBESITY IMPACT • 33% of the US population is obese and 70% is overweight • Over 17% of the children are obese • Health care costs over 147 billion a year MOUNT ROAD, CHENNAI, INDIA 1950s Now Known causes of obesity Environmental pollutants Genetics OBESITY Lack of exercise High calorie diet Stress Known causes of obesity Environmental pollutants Genetics OBESITY Lack of exercise High calorie diet Prenatal Stress Diet-induced obese (DIO) and Dietary resistant (DR) rats DIO • Polygenic model of obesity • DIO resembles human obesity in their tendency to gain weight on high energy diet • DR rats do not gain weight when placed on a HF diet DR Prenatal Stress Ø Known to contribute to adult diseases (Barker’s Hypothesis) Ø Chronic and acute prenatal stress paradigm Ø Prenatal stress in the context of maternal obesity has not been studied previously High Fat diet DR DIO Chow HF Diet • High fat diet intake associated with obesity • HF diet used 45% of calories came from fat Chow HF Diet Hypothesis ØPrenatal stress programs the offspring for obesity. STRESS DURING PREGNANCY ØDIO rats will be more susceptible to the effects of prenatal programming than DR animals. ØPostnatal HF diet challenge would make “programmed rats” more obese than controls DIO/DR rat Postnatal HF diet exposure OBESITY IN THE OFFSPRING Experimental Design Pregnant DIO/DR rat Control Acute Prenatal [Catheterisation surgery under Stress isoflurane anesthesia (once a week)] Male offspring Litter size and sex ratio normalized On chow/HF diet On chow diet Day of birth Weaning at Wk 3 Wk 9 Wk 10 Effects of acute and chronic prenatal stress on birth weight Acute stress during pregnancy increased post-weaning BW gain and calorie intake in DIO offspring Effects of HF diet challenge in programmed DIO and DR rats Effect of acute prenatal stress on VAT/BW ratio in the DIO and DR offspring Effect of acute Prenatal stress on HF dietinduced increase in blood glucose levels Effects of Acute prenatal stress on serum insulin levels in the DIO and DR offspring Insulin and metabolic syndrome Circulating insulin Circulating insulin CEACAM-1 in liver (Helps clear insulin from circulation) Decreased CEACAM-1 in liver Normal insulin levels Hyperinsulinemia Insulin resistance CEACAM-1/GAPDH CEACAM-1 expression in the liver DR DIO CEACAM1 GAPDH CEACAM1 GAPDH Prenatal stress Hyperactivation of stress axis NE in the PVN CRH in the median eminence Programming of feeding circuits? Increase in GR expression CORT and FFA to the liver via portal vein? 11βHSD1 expression Fat accumulation PEPCK enzyme expression? Fat accumulation in the liver? Insulin clearance? Increased food intake Altered balance between lipogenesis and lipolysis? LPL expression? HSL expression? Increased adipose tissue deposition Adiposity Hyperinsulinemia Metabolic syndrome in the offspring? Acknowledgements Collaborators Dr. P.S. MohanKumar Dr. Sonia Najjar, U Toledo Dr. Kate Claycombe, USDA Grads Dr. Priya Balasubramanian Dr. Ebony Gilbreath Dr. LakshmiKripa Jagannathan Undergrads Robert McGowan Melissa Seyerle Technician Katrina Linning Funding AG027697 CVM companion Animal fund
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