oral supplementations with lglutamine or lalanyllglutamine do not change metabolic alterations induced by longterm highfat diet in the b6129f2j mouse model of insulin resistance in this work we aimed to investigate the effects of longterm supplementations with lglutamine or lalanyllglutamine in the highfat diet hfdfed b6129sf2j mouse model over insulin sensitivity response and signaling oxidative stress markers metabolism and hsp70 expression mice were fed in a standard lowfat diet sta or a hfd for 20 weeks in the 21th week mice from the hfd group were allocated in five groups and supplemented for additional 8 weeks with different amino acids hfd control group hfdcon hfd dipeptide lalanyllglutamine group hfddip hfd lalanine group hfdala hfd lglutamine group hfdgln or the hfd lalanine lglutamine in their free forms group hfdala gln hfd induced higher body weight fat pad fasted glucose and total cholesterol in comparison with sta group amino acid supplementations did not induce any modifications in these parameters although insulin tolerance tests indicated insulin resistance in all hfd groups amino acid supplementations did not improve insulin sensitivity in the present model there were also no significant differences in the immunocontents of insulin receptor akt and tolllike receptor4 notably total 70 kda heat shock protein hsp72 hsp73 contents in the liver was markedly increased in hfdcon group as compared to sta group which might suggest that insulin resistance is only in the beginning apparently b6129sf2j mice are more resistant to the harmful effects of hfd through a mechanism that may include gut adaptation reducing the absorption of nutrients including amino acids which may explain the lack of improvements in our intervention