The Effect of Isoleucine Supplementation on Body Weight Gain and Blood Glucose Response in Lean and Obese Mice.

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

doi:10.3390/nu12082446

Abstract

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.

Highlights

The branched-chain amino acids (BCAAs), isoleucine, leucine and valine, are essential amino acids accounting for ~35% of the essential amino acids comprising muscle proteins in humans and ~40% of Nutrients 2020, 12, 2446; doi:10.3390/nu12082446 www.mdpi.com/journal/nutrientsNutrients 2020, 12, 2446 the pre-formed amino acids required by all mammals [1]
There was no difference in body weight between different treatment groups in mice fed a standard laboratory diet (SLD) or high-fat diet (HFD) prior to chronic isoleucine treatment (p < 0.0001, F (1, 50) = 28.17, diet effect; p = 0.1262, F (1, 50) = 2.418, isoleucine effect; SLD-C/A; 34.8 ± 0.7 g (n = 20), SLD-Ch; 37.2 ± 1.3 g (n = 10), HFD-C/A; 42.3 ± 1.6 g (n = 16), and HFD-Ch; 44.1 ± 1.7 g (n = 8))
In weeks 12–15, HFD-mice continued to gain more weight compared to SLD-mice (p < 0.0001, F (1, 50) = 19.21, diet effect; Figure 1A), but there was no effect of chronic isoleucine treatment on weight gain (Figure 1A)

Summary

Introduction

The branched-chain amino acids (BCAAs), isoleucine, leucine and valine, are essential amino acids accounting for ~35% of the essential amino acids comprising muscle proteins in humans and ~40% of Nutrients 2020, 12, 2446; doi:10.3390/nu12082446 www.mdpi.com/journal/nutrientsNutrients 2020, 12, 2446 the pre-formed amino acids required by all mammals [1]. An elevated dietary intake of BCAAs was associated with a lower prevalence of overweight and obesity in adults [2,3]. BCAA supplementation was demonstrated to preserve lean muscle mass during weight loss [4,5,6]. This evidence suggests a role for BCAA supplementation in the treatment of obesity. Chronic isoleucine supplementation in rodents has been demonstrated to prevent high-fat diet (HFD)-induced obesity [7]. Whether chronic isoleucine supplementation is an effective approach to ameliorate weight gain and promote weight loss in established obesity, is unknown

Objectives

Results

Discussion

Conclusion