Late gestation under- and overnutrition have differential impacts when combined with a post-natal obesogenic diet on glucose-lactate-insulin adaptations during metabolic challenges in adolescent sheep
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Late gestation under- and overnutrition have differential impacts when combined with a post-natal obesogenic diet on glucose-lactate-insulin adaptations during metabolic challenges in adolescent sheep. / Khanal, Prabhat ; Axel, Anne Marie Dixen; Kongsted, Anna Hauntoft; Husted, Sanne Vinter; Johnsen, Lærke; Pandey, Deepak; Pedersen, K. L.; Birtwistle, M.; Markussen, Bo; Kadarmideen, Haja; Nielsen, Mette Olaf.
I: Acta Physiologica (Print), Bind 213, Nr. 2, 2015, s. 519-536.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Late gestation under- and overnutrition have differential impacts when combined with a post-natal obesogenic diet on glucose-lactate-insulin adaptations during metabolic challenges in adolescent sheep
AU - Khanal, Prabhat
AU - Axel, Anne Marie Dixen
AU - Kongsted, Anna Hauntoft
AU - Husted, Sanne Vinter
AU - Johnsen, Lærke
AU - Pandey, Deepak
AU - Pedersen, K. L.
AU - Birtwistle, M.
AU - Markussen, Bo
AU - Kadarmideen, Haja
AU - Nielsen, Mette Olaf
N1 - © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
PY - 2015
Y1 - 2015
N2 - AIM: To determine whether late gestation under- and overnutrition programme metabolic plasticity in a similar way, and whether metabolic responses to an obesogenic diet in early post-natal life depend on the foetal nutrition history.METHODS: In a 3 × 2 factorial design, twin-pregnant ewes were for the last 6 weeks of gestation (term = 147 days) assigned to HIGH (N = 13; 150 and 110% of energy and protein requirements, respectively), NORM (N = 9; 100% of requirements) or LOW (N = 14; 50% of requirements) diets. The twin offspring were raised on high-carbohydrate-high-fat (HCHF; N = 35) or conventional (CONV; N = 35) diets from 3 days to 6 months of age (around puberty). Then intravenous glucose (GTT; overnight fasted), insulin (ITT; fed) and propionate (gluconeogenetic precursor; PTT; both fed and fasted) tolerance tests were conducted to evaluate (hepatic) metabolic plasticity.RESULTS: Prenatal malnutrition differentially impacted adaptations of particularly plasma lactate followed by glucose, cholesterol and insulin. This was most clearly expressed during PTT in fasted lambs and much less during ITT and GTT. In fasted lambs, propionate induced more dramatic increases in lactate than glucose, and HIGH lambs became more hyperglycaemic, hyperlactataemic and secreted less insulin compared to the hypercholesterolaemic LOW lambs. Propionate-induced insulin secretion was virtually abolished in fasted HCHF lambs, but upregulated in fasted compared to fed CONV lambs. HCHF lambs had the greatest glucose-induced insulin secretory responses.CONCLUSION: Prenatal malnutrition differentially programmed glucose-lactate metabolic pathways and cholesterol homeostasis. Prenatal overnutrition predisposed for hyperglycaemia and hyperlactataemia, whereas undernutrition predisposed for hypercholesterolaemia upon exposure to an obesogenic diet. Prenatal overnutrition (not undernutrition) interfered with pancreatic insulin secretion by non-glucose-dependent mechanisms.
AB - AIM: To determine whether late gestation under- and overnutrition programme metabolic plasticity in a similar way, and whether metabolic responses to an obesogenic diet in early post-natal life depend on the foetal nutrition history.METHODS: In a 3 × 2 factorial design, twin-pregnant ewes were for the last 6 weeks of gestation (term = 147 days) assigned to HIGH (N = 13; 150 and 110% of energy and protein requirements, respectively), NORM (N = 9; 100% of requirements) or LOW (N = 14; 50% of requirements) diets. The twin offspring were raised on high-carbohydrate-high-fat (HCHF; N = 35) or conventional (CONV; N = 35) diets from 3 days to 6 months of age (around puberty). Then intravenous glucose (GTT; overnight fasted), insulin (ITT; fed) and propionate (gluconeogenetic precursor; PTT; both fed and fasted) tolerance tests were conducted to evaluate (hepatic) metabolic plasticity.RESULTS: Prenatal malnutrition differentially impacted adaptations of particularly plasma lactate followed by glucose, cholesterol and insulin. This was most clearly expressed during PTT in fasted lambs and much less during ITT and GTT. In fasted lambs, propionate induced more dramatic increases in lactate than glucose, and HIGH lambs became more hyperglycaemic, hyperlactataemic and secreted less insulin compared to the hypercholesterolaemic LOW lambs. Propionate-induced insulin secretion was virtually abolished in fasted HCHF lambs, but upregulated in fasted compared to fed CONV lambs. HCHF lambs had the greatest glucose-induced insulin secretory responses.CONCLUSION: Prenatal malnutrition differentially programmed glucose-lactate metabolic pathways and cholesterol homeostasis. Prenatal overnutrition predisposed for hyperglycaemia and hyperlactataemia, whereas undernutrition predisposed for hypercholesterolaemia upon exposure to an obesogenic diet. Prenatal overnutrition (not undernutrition) interfered with pancreatic insulin secretion by non-glucose-dependent mechanisms.
U2 - 10.1111/apha.12391
DO - 10.1111/apha.12391
M3 - Journal article
C2 - 25204637
VL - 213
SP - 519
EP - 536
JO - Acta Physiologica
JF - Acta Physiologica
SN - 1748-1708
IS - 2
ER -
ID: 130795050