EXCESSIVE MATERNAL WEIGHT GAIN DURING GESTATION LEADS TO OFFSPRING - PowerPoint PPT Presentation

Note: for non-commercial purposes only EXCESSIVE MATERNAL WEIGHT GAIN DURING GESTATION LEADS TO OFFSPRING WITH INCREASED ADIPOGENIC POTENTIAL IN THE IMMEDIATE PERINATAL PERIOD IN PIGS Kolapo M Ajuwon, Emily J Arentson, Shawn S Donkin Department of Animal Sciences, Purdue University Funding: The Showalter Trust Fund

Gestational weight gain in the U.S.  Institute of Medicine recommendations Recommended GWG decreases with increasing prepregnancy BMI  Approximately 20% of all pregnancies in the US gain more than the recommended amount of weight. Overweight and obese women are at particular risk.  Excess weight gain presents health risks for both mother and offspring

Pig Model  Pig model serves as a good bridge between mouse and humans  Studies in mice can be replicated in pigs

Perinatal Nutrition in Pigs Piglet diet before weaning can be manipulated to cause maximum epigenetic effects during the perinatal period

Study hypotheses Excess maternal weight gain Hypothesis 2: Hypothesis 1: Early postnatal nutrition Excessive weight gain has the ability reverse during pregnancy due Altered body or enhance the effect of to increased energy composition, maternal diet. disturbed glucose intake will result in homeostasis programming modifications that Early life metabolic predispose offspring to adaptations obesity and aspects of the metabolic syndrome. Increased childhood adiposity High fat diet Metabolic syndrome

Study Design Maternal groups Post-weaning groups Maternal Diets : m-Control: chow Post-weaning Control gestation diet Diets : M-HE: high energy Control: chow m-Control gestation diet piglet diets - Increased energy HE HE: high fat intake (kcal) by piglet diets ~50% - Increased fat - Matched for content of diet by protein intake 10-15% Control (g/day) M-HE mNEwHE HE n=9

Experimental methods for determining programming of offspring • Adipose, Liver & intestine mRNA for transcript analysis Weaning: assigned to • Serum for glucose, insulin post-weaning (Pwn) diet and NEFA analysis Growth phase (9 weeks) Suckling period • Weights measured every 1-2 weeks 12 weeks Birth 3 weeks

High energy diet increased maternal weight gain and adiposity during gestation *P<0.05 50 *P<0.05 10 Gestational weight gain (kg) 40 Gestational backfat gain (mm) 8 30 6 20 4 10 2 0 0 M-Control m-HE M-Control m-HE

Offspring from sows fed a HE diet weighed more at 8 and 10 weeks of age. Increased childhood 40 m-HE adiposity m-NE * Weight (kg) 30 Main effect P-value † Mat 0.12 mNEwNE 20 Pwn 0.93 mNEwHE Mat*Pwn 0.85 mHEwNE 10 Day <0.05 mHEwHE 0 Mat*Pwn*Day 0.95 12 21 41 61 81 9 3 6 Weeks Day

Feeding a HF diet to offspring from HF diet fed sows induced disturbed offspring glucose homeostasis Metabolic syndrome Maternal Diet M-Control M-HE P-Values p-Control p-HE p-Control P-HE CI Mat Pst.natal M x P Glucose (67.3, 70 80 64 102* † 0.47 <0.05 0.21 (mg/dl) 90.9) Insulin (0.011, 0.021 † 0.016 0.013 0.010 0.92 0.24 0.08 (ng/ml) 0.019) NEFA 0.43 0.43 0.62 0.31* (0.34,0.56) 0.87 0.12 0.11 (mmol/L) † Significantly different (P<0.05) from control group of the maternal group (mHE → wNE) * Significantly different (P<0.05) from offspring of control dams fed the same post-weaning diet (mNE → wHE)

Adipose CEBP α and PPAR γ at 48 hr 1,600 1,600 1,400 CEBP α/18 S D1 SC fat PAPR γ/18 S D1 SC fat 1,400 1,200 1,200 1,000 1,000 0,800 0,800 0,600 0,600 0,400 0,400 0,200 0,200 0,000 0,000 HE NE Control Control HE NE

Adipose SFRP2 at 48hr SFRP 2,500 SFRP2/18S D1 SC fat a 2,000 1,500 b 1,000 0,500 0,000 HE NE Control

Adipose SFRP4 and SFRP5 at 3 wks a 2,000 2,500 SFRP5/18S D21 SC fat a SFRP4/18S D21 SC 2,000 1,500 b 1,500 fat 1,000 b 1,000 0,500 0,500 0,000 0,000 HE NE Control Control HE NE

Adipose CEBP α and PPAR γ at 3 wks a 3,500 3,000 CEBP α/18 S D21 SC fat a PPAR γ/18 S D21 SC fat 3,000 2,500 2,500 2,000 2,000 1,500 1,500 1,000 1,000 b b 0,500 0,500 0,000 0,000 Control HE NE HE NE Control

At 3 Months 35 25 30 20 25 Back Fat (mm) BW (kg) 15 20 15 10 10 5 5 0 0 M HE M Control M HE M Control 25 35 P=0.14 30 20 Back Fat (mm) 25 15 BW (kg) 20 15 10 10 5 5 0 0 P HE P Control P HE P Control

Adipose SFRP5 at 3 Mon 1,800 2,500 1,600 SFRP5/18S at 3 Mon a SFRP5/18S 3 Mon 1,400 2,000 1,200 1,500 1,000 b 0,800 1,000 0,600 0,400 0,500 0,200 0,000 0,000 M Control P Control P HE P NE M HE M NE

Adipose PPAR γ at 3 Mon 1,400 1,400 PPAR γ/18 S at 3 Mon PPAR γ/18 S at 3 Mon 1,200 1,200 1,000 1,000 0,800 0,800 0,600 0,600 0,400 0,400 0,200 0,200 0,000 0,000 M HE M NE M Control P HE P Control P NE 1,400 1,200 PPAR γ/18 S at 3 Mon 1,000 0,800 0,600 0,400 0,200 0,000 HE HE HE NE NE HE NE NE

Adipose CEBP α at 3 Mon 1,400 1,400 CEBP α/18 S fat 3 Mon 1,200 CEBP α/18 S at 3 Mon 1,200 1,000 1,000 0,800 0,800 0,600 0,600 0,400 0,400 0,200 0,200 0,000 0,000 M Control M HE M NE P HE P Control P NE 1,600 1,400 CEBP α/18 S at 3 Mon 1,200 1,000 0,800 0,600 0,400 0,200 0,000 HE HE HE NE NE HE NE NE

Summary  Offspring of mothers that gained excess weight during pregnancy:  Weighed more at 8 weeks and 10 weeks of age, although were not significantly different at the end of the study  Had higher expression of increased adipogenesis at 48 hr (SFRP2) and 3 wks (CEBP α , PPAR γ , SFRP4, and SFRP5).  These indicators were lost at 12 wks  Pigs were still relatively young at sacrifice, so this might not be a good time to see the final effect of fetal programming in pigs  Postnatal diet might play a more dominant role in the determination of offspring adiposity in pigs.

Questions?

Relative abundance of liver transcripts at 12 wks Early life metabolic & growth adaptations 3 *P<0.05 Pepck relative abundance 2,5 2 1,5 1 0,5 Control 0 p-NE p-HE p-NE p-HE mNE mHE M Control M HE Arentsen et al., 2014 Nutrition Research (In Press)

Maternal Gestation Nutrient Intake Control High Energy Total intake, kg/day 2.05 3.0 Total Protein, g/day 370 395 Total Lysine, g/day 16.03 15.8 Total Fat, g/day 119 178 Metabolizable Energy, kcal/day 6761 10144