The effect of isoleucine supplementation on body weight gain and blood glucose response in lean and obese mice

Rebecca O’Rielly, Hui Li, See Meng Lim, Roger Yazbeck, Stamatiki Kritas, Sina S. Ullrich, Christine Feinle-Bisset, Leonie Heilbronn, Amanda J. Page

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Chronic isoleucine supplementation prevents diet-induced weight gain in rodents. Acute-isoleucine administration improves glucose tolerance in rodents and reduces postprandial glucose levels in humans. However, the effect of chronic-isoleucine supplementation on body weight and glucose tolerance in obesity is unknown. This study aimed to investigate the impact of chronic isoleucine on body weight gain and glucose tolerance in lean and high-fat-diet (HFD) induced-obese mice. Male C57BL/6-mice, fed a standard-laboratory-diet (SLD) or HFD for 12 weeks, were randomly allocated to: (1) Control: Drinking water; (2) Acute: Drinking water with a gavage of isoleucine (300 mg/kg) prior to the oral-glucose-tolerance-test (OGTT) or gastric-emptying-breath-test (GEBT); (3) Chronic: Drinking water with 1.5% isoleucine, for a further six weeks. At 16 weeks, an OGTT and GEBT was performed and at 17 weeks metabolic monitoring. In SLD-and HFD-mice, there was no difference in body weight, fat mass, and plasma lipid profiles between isoleucine treatment groups. Acute-isoleucine did not improve glucose tolerance in SLD-or HFD-mice. Chronic-isoleucine impaired glucose tolerance in SLD-mice. There was no difference in gastric emptying between any groups. Chronic-isoleucine did not alter energy intake, energy expenditure, or respiratory quotient in SLD-or HFD-mice. In conclusion, chronic isoleucine supplementation may not be an effective treatment for obesity or glucose intolerance.

Original languageEnglish
Article number2446
Number of pages12
Issue number8
Publication statusPublished - Aug 2020

Bibliographical note

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution(CC BY) license (


  • Amino acid
  • Chronic supplementation
  • Energy expenditure
  • Gastric emptying breath test
  • Glycaemic control
  • Isoleucine
  • Obesity
  • Oral glucose tolerance test


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