204: Impact of maternal diet on peripheral vs hepatic insulin resistance in young female offspring

Abstract

insulin resistance in young female offspring Hye Heo, Howard Slomko, Scarlett Karakash, Fabien Delahaye, Yongmei Zhao, Derek Huffman, Nir Barzilai, Francine Einstein Albert Einstein College of Medicine/Montefiore Medical Center, Obstetrics & Gynecology and Women’s Health, Bronx, NY, Albert Einstein College of Medicine/Montefiore Medical Center, Pediatrics, Bronx, NY, Albert Einstein College of Medicine, Medicine, Bronx, NY, Albert Einstein College of Medicine/Montefiore Medical Center, Obstetrics & Gynecology and Women’s Health, Bronx, NY OBJECTIVE: To characterize body composition and metabolic phenotype of young female offspring exposed to maternal western diet and calorie restriction (CR). STUDY DESIGN: SD female rats were fed 1 of 3 diets: 1) standard chow (Con-M), 2) western diet from 3 wks through gestation/lactation (WD-M) or 3) standard chow from 3 wks until Day 11 of gestation, then calorie restricted (pair-fed 50% kcal/d of Con-M) through lactation (CR-M). Litters were culled to 8pups. Female offspring (n 9/ grp, Con-F, WD-F and CR-F) were given standard chow after weaning. Body composition (microCT) was assessed at 4 and 6 weeks of life. At 9wks, insulin sensitivity was measured by hyperinsulinemic (3mU/ kg/min) clamp technique, using somatostatin (1.5ug/kg/min) and 3H3-glucose (to follow glucose flux). RESULTS: Maternal calorie intake (kcal/d/kg) and weight were similar in Con-M and WD-M. Litter size, pup and placental weight were similar in all groups. At weaning, WD-F weighed more and had greater SC/VF ratio compared to Con-F, but no differences in total fat. CR-F weighed less and had less total fat at weaning and did not catch up in growth. By 6wks, weight and fat distribution normalized in WD-F compared to Con-F. Both WD-F and CR-F consumed more calories for body weight compared to Con-F during the study, but normalized at 9 wks (Fig 1). Clamp results shown in Table 1. Glucose infusion rate was lower in both WD-F and CR-F. While CR-F had greater hepatic insulin resistance (less suppression of hepatic glucose production (HGP)), HGP was similar in WD-F compared to Con-F. Peripheral insulin sensitivity (Rd) was lower in WD-F, but this did not reach statistical significance. CONCLUSION: Western diet alone (i.e. without changes in maternal body weight) leads to insulin resistance in the young female rat offspring similar to the degree seen with severe maternal CR. Unlike offspring of WD dams, offspring of CR dams have greater degree of hepatic insulin resistance. The mechanism for differences in hepatic vs peripheral insulin resistance requires further study. *p 0.05. 205 Sedentary behavior during pregnancy does not alter maternal fat distribution or insulin action Hye Heo, Scarlett Karakash, Derek Huffman, Fabien Delahaye, Yongmei Zhao, Nir Barzilai, Francine Einstein Albert Einstein College of Medicine/Montefiore Medical Center, Obstetrics & Gynecology and Women’s Health, Bronx, NY, Albert Einstein College of Medicine, Medicine, Bronx, NY, Albert Einstein College of Medicine/Montefiore Medical Center, Obstetrics & Gynecology and Women’s Health, Bronx, NY OBJECTIVE: To determine the effects of voluntary exercise on insulin action and body composition in young pregnant and non-pregnant female rodents. STUDY DESIGN: Four groups of lean, age-matched SD rats were studied (n 5/group): non-pregnant controls (NPC), non-pregnant sedentary (NPS), pregnant controls (PC), and pregnant sedentary (PS). PC had continuous voluntary access to running wheels starting Day 1 of a 22 day gestation. PS were housed in similar cages without access to the running apparatus. At day 19, insulin sensitivity was assessed by hyperinsulinemic-euglycemic (3mU/kg/min) clamp technique, using somatostatin (1.5ug/kg/min) and 3H3-glucose (to follow glucose flux). A bolus of 2-[U-14C]deoxyglucose (20 Ci) was administered 30 min before the end of the clamp to determine tissue glucose uptake. To study chronic effects of exercise (as opposed to acute effects), wheel breaks were placed 18 hrs prior to insulin clamps. Animals were sacrificed at end of the clamp and tissues were collected and weighed. RESULTS: NPS had similar food intake, but greater visceral fat (3.0 .3 v 1.7 .4g; p 0.05) compared to NPC. PS and PC also had similar food intake, but no significant differences in visceral fat. PS and PC had no differences in pup weight, litter size, or glucose uptake in placenta, pups or maternal muscle. PC ran approximately 1/4 of the distance that NPC ran (9,434 1,593 v 36,235 11,517m; p 0.059). During insulin clamps (Table 1), overall insulin sensitivity, measured by glucose infusion rate (GIR) was not statistically different in NPS and NPC. In NPS, peripheral insulin sensitivity (Rd) was similar, but hepatic glucose production (HGP) was greater compared to NPC. GIR, Rd and HGP were similar in PS and PC. CONCLUSION: Sedentary behavior in non-pregnant, young female rodents is associated with increased visceral adiposity and hepatic insulin resistance. This effect is not seen in sedentary pregnant animals most likely because voluntary activity is decreased in pregnancy. *p 0.05. www.AJOG.org Clinical Obstetrics, Medical-Surgical-Disease, Neonatology, Physiology-Endocrinology Poster Session I