Excessive Tryptophan and Phenylalanine Induced Pancreatic Injury and Glycometabolism Disorder in Grower-finisher Pigs.

BACKGROUND: The increase in circulating insulin levels is associated with the onset of type 2 diabetes (T2D), and the levels of branched-chain amino acids and aromatic amino acids (AAAs) are altered in T2D, but whether AAAs play a role in insulin secretion and signaling remains unclear. OBJECTIVES: This study aimed to investigate the effects of different AAAs on pancreatic function and on the use of insulin in finishing pigs. METHODS: A total of 18 healthy finishing pigs (Large White) with average body weight of 100 ± 1.15 kg were randomly allocated to 3 dietary treatments: Con, a normal diet supplemented with 0.68% alanine; Phe, a normal diet supplemented with 1.26% phenylalanine; and Trp, a normal diet supplemented with 0.78% tryptophan. The 3 diets were isonitrogenous. There were 6 replicates in each group. RESULTS: Herein, we investigated the effects of tryptophan and phenylalanine on pancreatic function and the use of insulin in finishing pigs and found that the addition of tryptophan and phenylalanine aggravated pancreatic fat deposition, increased the relative content of saturated fatty acids, especially palmitate (C16:0) and stearate (C18:0), and the resulting lipid toxicity disrupted pancreatic secretory function. We also found that tryptophan and phenylalanine inhibited the growth and secretion of ß-cells, downregulated the gene expression of the PI3K/Akt pathway in the pancreas and liver, and reduced glucose utilization in the liver. CONCLUSIONS: Using fattening pigs as a model, multiorgan combined analysis of the insulin-secreting organ pancreas and the main insulin-acting organ liver, excessive intake of tryptophan and phenylalanine will aggravate pancreatic damage leading to glucose metabolism disorders, providing new evidence for the occurrence and development of T2D.

Threonine supplementation prevents the development of fat deposition in mice fed a high-fat diet.

Obesity is the main factor involved in the onset of many diseases. Threonine supplementation has been demonstrated to reduce fat mass and serum triglycerides in already obese mice. However, it is unclear whether threonine could inhibit the development of obesity in mice without previous high-fat diet induction. In the present study, mice were fed a chow diet (CD) or a high-fat diet (HFD), supplemented or not with threonine (3.0% in drinking water) for 15 weeks. Results showed that mice subjected to chronic threonine supplementation showed decreased body weight, epididymal white adipose tissue weight, serum low-density lipoprotein cholesterol, and total cholesterol in comparison with HFD-fed mice. In the epididymal adipose tissue, gene expressions of sterol regulatory element-binding protein 1c and fatty acid synthase were up-regulated, while hormone sensitive lipase, adiponectin and fibroblast growth factor 21 were down-regulated. In the liver tissue, gene expressions of sirtuin1, adenosine monophosphate-activated protein kinase and peroxisome proliferator activated receptor γ co-activator 1α were up-regulated by threonine supplementation in HFD-fed mice. These results suggest that long-term threonine supplementation inhibited fat mass and improved lipid metabolism, making it a potential agent to prevent the development of diet-induced obesity.