Dietary Valine Ameliorated Gut Health and Accelerated the Development of Nonalcoholic Fatty Liver Disease of Laying Hens

Abstract

Valine is an important essential amino acid of laying hens. Dietary supplemented with BCAAs ameliorated gut microbiota, whereas elevated blood levels of BCAAs are positively associated with obesity, insulin resistance, and diabetes in both humans and rodents. General controlled nonrepressed (GCN2) kinase plays a crucial role in regulating intestinal inflammation and hepatic fatty acid homeostasis during amino acids deficiency, while GCN2 deficient results in enhanced intestinal inflammation and developed hepatic steatosis. However, how long-term dietary valine impacts gut health and the development of nonalcoholic fatty liver disease (NAFLD) remains unknown. Hence, in the present study, we elucidated the effects of dietary valine on intestinal barrier function, microbial homeostasis, and the development of NAFLD. A total of 960 healthy 33-weeks-old laying hens were randomly divided into five experimental groups and fed with valine at the following different levels in a feeding trial that lasted 8 weeks: 0.59, 0.64, 0.69, 0.74, and 0.79%, respectively. After 8 weeks of treatment, related tissues and cecal contents were obtained for further analysis. The results showed that diet supplemented with valine ameliorated gut health by improving intestinal villus morphology, enhancing intestinal barrier, decreasing cecum pathogenic bacteria abundances such as Fusobacteriota and Deferribacterota, and inhibiting inflammatory response mediated by GCN2. However, long-term intake of high levels of dietary valine (0.74 and 0.79%) accelerated the development of NAFLD of laying hens by promoting lipogenesis and inhibiting fatty acid oxidation mediated by GCN2-eIF2α-ATF4. Furthermore, NAFLD induced by high levels of dietary valine (0.74 and 0.79%) resulted in strengthening oxidative stress, ER stress, and inflammatory response. Our results revealed that high levels of valine are a key regulator of gut health and the adverse metabolic response to NAFLD and suggested reducing dietary valine as a new approach to preventing NAFLD of laying hens.

Alterations in Intestinal Antioxidant and Immune Function and Cecal Microbiota of Laying Hens Fed on Coated Sodium Butyrate Supplemented Diets

“…The metabolism of various cells in the body produces a large number of reactive oxygen species and other substances. Laying hens are susceptible to producing excessive reactive oxygen species leading to intestinal oxidative stress due to the genetic selection for long-laying eggs [ 20 ]. Sufficient studies have proved that butyrate performed powerful antioxidant functions whether in vivo or in vitro [ 21 , 22 , 23 , 24 ].…”

Amino Acid and Fatty Acid Metabolism Disorders Trigger Oxidative Stress and Inflammatory Response in Excessive Dietary Valine-Induced NAFLD of Laying Hens

“…As a substrate for the synthesis of TG, fatty acids can be esterified with glycerol sterol backbones, generating TGs or sterol esters (SEs), respectively, and then stored in LDs ( 36 ). Our recent report indicated dietary valine treatment dramatically increased the concentration of TG in the serum and liver with increasing dietary levels ( 33 ). We first investigated the effects of dietary valine on liver fatty acid synthesis, and we found that dietary valine supplementation dramatically improved the contents of liver ACLY, NEFA, HDL, and VLDL ( P < 0.05) ( Figures 2C,D,E,G ), whereas the content of liver FASN showed an increase first and then decreased with the increase of dietary valine levels ( P < 0.05) ( Figure 2A ).…”

“…Our recent reports demonstrated that diet-supplemented valine has significantly altered the serum-free amino acid profile of laying hens. Additionally, long-term exposure to high levels of dietary valine at 0.74 and 0.79% has accelerated the development of NAFLD of laying hens by promoting lipogenesis and inhibiting fatty acid oxidation mediated by GCN2-eIF2α-activating transcription factor 4 (ATF4) ( 32 , 33 ). NAFLD induced by excessive dietary valine resulted in strengthening oxidative stress, ER stress, and inflammatory response ( 32 , 33 ).…”

“…Additionally, long-term exposure to high levels of dietary valine at 0.74 and 0.79% has accelerated the development of NAFLD of laying hens by promoting lipogenesis and inhibiting fatty acid oxidation mediated by GCN2-eIF2α-activating transcription factor 4 (ATF4) ( 32 , 33 ). NAFLD induced by excessive dietary valine resulted in strengthening oxidative stress, ER stress, and inflammatory response ( 32 , 33 ). Nevertheless, a comprehensive investigation of the roles of dietary valine in the change of amino acid profile and fatty acid metabolism in NAFLD has not been fully pursued.…”

Functional role of branched chain amino acids in poultry: a review

“…and C. perfringens require leucine and isoleucine for their growth whereas Escherichia coli do not depend on these AA and thus the variability in the supply of such AA could favor certain groups of bacteria in their competitiveness against others in the GIT of poultry. Jian et al. (2021b) studied the effect of supplemental valine fed to 33-wk-old laying hens where basal control diet contained 0.59% total valine and the supplemented diet had 0.79% valine.…”