Endocrine Abstracts

Plasma cortisol and methyl group metabolism in lean and obese sheep before and after feeding

DS Gardner¹, R Singh², ME Symonds¹ & KD Sinclair²

¹ School of Human Development, University of Nottingham, Nottingham, United Kingdom, ²School of Biosciences, University of Nottingham, Loughborough, United Kingdom

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Background: Programmed disruption of the methionine cycle elevates plasma homocysteine concentrations leading to cardiovascular disease (CVD). Elements of this cycle are glucocorticoid responsive. Here we measured plasma cortisol, cysteine, homocysteine, glutathione and its breakdown product cysteinyl-glycine in the fed and fasted state in sheep.

Methods: 37 twin-bearing ewes were randomly allocated to receive either a control (C, n=24) or nutrient restricted diet (NR, 50% C intake, n=13) from days 30 to 80 of gestation. Thereafter all sheep were fed to 100% requirement to term (12–13 MJ/day). Offspring were delivered spontaneously and either ewe reared or bottle-fed (BF, n=8 from control group; 1–1.5 L/d Volac) until weaning (10–12 weeks). Thereafter to 1yr offspring were reared indoors with restricted activity and increased food availability to promote fat deposition (Obese controls OC, n=8; Obese nutrient restricted ONR, n=13; Obese bottle-fed OBF, n=8) or pasture grazed with unrestricted activity (Lean controls LC, n=8). Blood was regularly sampled during the fed and fasted state over a 24 h period. Plasma was analysed for cortisol by RIA and thiol status by HPLC.

Results: In the fasted state, plasma cysteine was elevated in all obese relative to lean sheep (∼185 μM vs. 131 μM), but homocysteine was elevated in obese bottle-fed sheep only (∼19±2 μM vs. 12±1 μM in other groups). Regardless of group higher thiol values were observed during the fed rather than fasted state. Fasted plasma cortisol was similar between groups (range 27–43 nM). After 2 h feeding, values remained unchanged from baseline in all groups except OBF which markedly increased (delta cortisol: 82±48 nM).

Conclusions: Bottle-fed obese sheep have higher resting plasma homocysteine concentrations relative to other obese and lean sheep and a greater cortisol response to feeding. Plasma homocysteine concentrations greater than 15 μM in humans predict increased risk of CVD. Increased plasma cysteine concentrations in obese relative to lean sheep suggests a predisposition to remove homocysteine from the circulation via the trans-sulphuration pathway in this physiological state.

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Endocrine Abstracts (2005) 10 P43