Alanylglutamine

Glutamine availability may be reduced in chronic diseases, such as type 2 diabetes mellitus (T2DM)-induced by obesity. Herein, the antioxidant, anti-inflammatory and lipid metabolism effects of chronic oral glutamine supplementation in its free and dipeptide form were assessed in ob/ob mice. Adult male C57BL/6J ob/ob mice were supplemented with L-alanyl-L-glutamine (DIP) or free L-glutamine (GLN) in the drinking water for 40 days, whilst C57BL/6J Wild-type lean (WT) and control ob/ob mice (CTRL) received fresh water only. Plasma and tissue (skeletal muscle and liver) glutamine levels, and insulin resistance parameters (e.g., GTT, ITT, insulin) were determined. Oxidative stress (e.g., GSH system, Nrf2 translocation), inflammatory (e.g., NFkB translocation, TNF-α gene expression) and lipid metabolism parameters (e.g., plasma and liver triglyceride levels, SRBP-1, FAS, ACC, and ChRBP gene expression) were also analyzed. CTRL ob/ob mice showed lower glutamine levels in plasma and tissue, as well as increased insulin resistance and fat in the liver. Conversely, chronic DIP supplementation restored glutamine levels in plasma and tissues, improved glucose homeostasis and reduced plasma and liver lipid levels. Also, Nrf2 restoration, reduced NFkB translocation, and lower TNF-α gene expression was observed in the DIP group. Interestingly, chronic free GLN only increased muscle glutamine stores but reduced overall insulin resistance, and attenuated plasma and liver lipid metabolic biomarkers. The results presented herein indicate that restoration of body glutamine levels reduces oxidative stress and inflammation in obese and T2DM ob/ob mice. This effect attenuated hepatic lipid metabolic changes observed in obesity.

Crabs marketed off-season in lunar June often have a brown hepatopancreas (BH) that tastes bitter, unlike the nonbitter orange hepatopancreas (OH). We conducted nontargeted and widely targeted metabolomics analyses on both raw and cooked orange and brown hepatopancreas of Eriocheir sinensis. A total of 115 bitter metabolites were identified, including oxylipins, amino acids, small peptides, nucleotides, vitamins, and coenzymes. Targeted quantitative analysis revealed that seven oxylipins were major contributors to the bitterness of BH. The primary metabolic pathways affecting hepatopancreas bitterness involved the production of unsaturated fatty acids and α-linolenic acid metabolism. Furthermore, specific odorants were produced from OH and BH groups during heat treatment, namely ethyl caproate and methional, respectively. Moreover, differential metabolites were found to act as odor precursors, resulting in a brown and bitter hepatopancreas with poor odor quality. This study elucidates the generation of bitter substances in the hepatopancreas of Eriocheir sinensis through metabolic pathways and thermal reaction pathways.