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Food Overconsumption in Healthy Adults Triggers Early and Sustained Increases in Serum Branched-Chain Amino Acids and Changes in Cysteine Linked to Fat Gain
Univ Alexandria, Dept Physiol, Fac Med, Alexandria, Egypt.
Garvan Inst Med Res, Diabet & Metab Div, Sydney, NSW, Australia;Univ New South Wales, Fac Med, Sydney, NSW, Australia.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Univ Oxford, Dept Pharmacol, Oxford, England.
Univ Oxford, Dept Pharmacol, Oxford, England.
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2018 (English)In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 148, no 7, p. 1073-1080Article in journal (Refereed) Published
Abstract [en]

Background: Plasma concentrations of branched-chain amino acids (BCAAs) and the sulfur-containing amino acid cysteine are associated with obesity and insulin resistance. BCAAs predict future diabetes. Objective: We investigated amino acid changes during food overconsumption. Methods: Forty healthy men and women with a body mass index (mean +/- SEM) of 25.6 +/- 0.6 were overfed by 1250 kcal/d for 28 d, increasing consumption of all macronutrients. Insulin sensitivity and body composition were assessed at baseline (day 0) and day 28. Fasting serum amino acids were measured at days 0, 3, and 28. Linear mixed-effects models evaluated the effect of time in the total group and separately in those with low and high body fat gain (below compared with at or above median fat gain, 1.95 kg). At days 0 and 28, insulin-induced suppression of serum amino acids during a hyperinsulinemic-euglycemic clamp test and, in a subset (n = 20), adipose tissue mRNA expression of selected amino acid metabolizing enzymes were assessed. Results: Weight increased by 2.8 kg. High fat gainers gained 2.6 kg fat mass compared with 1.1 kg in low fat gainers. Valine and isoleucine increased at day 3 (+17% and +22%, respectively; P <= 0.002) and remained elevated at day 28, despite a decline in valine (P = 0.019) from day 3 values. Methionine, cystathionine, and taurine were unaffected. Serum total cysteine (tCys) transiently increased at day 3 (+11%; P = 0.022) only in high fat gainers (P-interaction = 0.043), in whom the cysteine catabolic enzyme cysteine dioxygenase (CDO1) was induced (+26%; P = 0.025) in adipose tissue (P-interaction = 0.045). Overconsumption did not alter adipose tissue mRNA expression of the BCAA-metabolizing enzymes branched-chain keto acid dehydrogenase E1 alpha polypeptide (BCKDHA) or branched-chain amino transferase 1 (BCAT1). In the total population at day 0, insulin infusion decreased all serum amino acids (-11% to -47%; P < 0.01), except for homocysteine and tCys, which were unchanged, and glutathione, which was increased by 54%. At day 28, insulin increased tCys (+8%), and the insulin-induced suppression of taurine and phenylalanine observed at day 0, but not that of BCAAs, was significantly impaired. Conclusions: These findings highlight the role of nutrient oversupply in increasing fasting BCAA concentrations in healthy adults. The link between cysteine availability, CDO1 expression, and fat gain deserves investigation.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS , 2018. Vol. 148, no 7, p. 1073-1080
Keywords [en]
tandem mass spectrometry, DXA, BCAT, BCKD, aromatic amino acids, fat gain, high caloric intake
National Category
Nutrition and Dietetics
Identifiers
URN: urn:nbn:se:uu:diva-361098DOI: 10.1093/jn/nxy062ISI: 000438099300003PubMedID: 29901727OAI: oai:DiVA.org:uu-361098DiVA, id: diva2:1250165
Available from: 2018-09-21 Created: 2018-09-21 Last updated: 2018-09-21Bibliographically approved

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Jernerén, Fredrik

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