Background: Dietary consumption of branched chain amino acids, including L-isoleucine, has been inversely associated with obesity in humans(1). Acute L-isoleucine supplementation in standard laboratory diet (SLD) and high fat diet (HFD) fed rodents has been demonstrated to improve glucose tolerance, however, the effect of chronic isoleucine supplementation on glucose tolerance is unknown(2). Therefore, we aimed to investigate the effect of chronic L-isoleucine supplementation on body weight and glucose tolerance in SLD and HFD-induced obese mice.
Methods: Male C57BL/6 mice (n=60,8wks old) housed in a 12h light-dark cycle were allocated into 2 groups and fed either a SLD (14%kJ from fat) or a HFD (60%kJ from fat) for 17wks. After 12wks, mice were allocated into 3 groups/diet (n=10/group) and provided either normal drinking water (Control(C) & Acute(A)) or drinking water supplemented with 1.5% L-isoleucine (Chronic(Ch)) for the remaining 4wks. At 17wks, fasted mice received an oral gavage (0.1ml/10g body weight (BW)) of either normal water (C&Ch) or 300mg/kg L-isoleucine (A) 30min prior to an oral glucose tolerance test (OGTT;1g/kg BW).
Results: At 12wks, HFD mice had gained more weight than SLD mice (SLD:7.99±0.34g, HFD:15.55±1.67g; unpaired-t-test(P=0.0002). Between 13&16wks, HFD mice gained more weight than SLD mice but there was no difference in weight gain within dietary groups despite L-isoleucine treatment (SLD:C,1.58± 0.26g; A,2.40± 0.25g; Ch,2.49± 0.34g; HFD:C,3.19±0.44g; A,4.59±0.44g; Ch,4.44±0.85g; 2way-ANOVA(P<0.0001)Dietary-effect). At 17wks, fasting blood glucose was elevated in HFD mice compared to SLD mice but there was no L-isoleucine effect (SLD:C,10.84±0.50mmol/l; A,10.50±0.31mmol/l; Ch,11.15±0.48mmol/l; HFD:C,12.61±0.60mmol/l; A,12.90±0.70mmol/L; Ch,12.81±0.66mmol/l;2way-ANOVA(P<0.000)Dietary-effect). The OGTT blood glucose area under the curve was elevated in HFD compared to SLD mice but there was no L-isoleucine effect within dietary groups (SLD:C,1651±109.0mmol/l-min; A,1760±95.81mmol/l-min; Ch,1980± 170.8mmol/l-min; HFD:C,2228±174.1mmol/l-min; A,2162±191mmol/l-min; Ch,2416±232mmol/l-min;2way-ANOVA(P=0.0022)Dietary-effect).
Conclusion: Acute and chronic supplementation with L-isoleucine had no effect on body weight gain or glucose tolerance in SLD mice or HFD induced-obese mice.