Dietary Valine Ameliorated Gut Health and Accelerated the Development of Nonalcoholic Fatty Liver Disease of Laying Hens - PubMed (original) (raw)

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

Huafeng Jian et al. Oxid Med Cell Longev. 2021.

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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-eIF2_α_-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.

Copyright © 2021 Huafeng Jian et al.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Figure 1

Effects of dietary valine supplementation on villi morphology of small intestine of laying hens (n = 6). (a) Villus height. (b) Crypt depth. (c) Villus height/crypt depth (V/C). (d) Duodenum. (e) Jejunum. (f) Ileum. A-DMeans with different superscripts within a column differ significantly (P < 0.05).

Figure 2

Figure 2

Dietary valine treatment changed the composition and structure of cecal microbiota of laying hens (n = 6). (a)–(c) The microbial beta diversity was accessed by principal component analysis (PCA), principal coordinate analysis (PCoA), and nonmetric multidimensional scaling (NMDS) analysis based on the OTU level. (d) Relative abundance > 1% of bacterial phyla. (e) Relative abundance of class level. (f) Relative abundance of order level. (g)–(i) The relative abundance of significant differential bacteria on phylum, class, and order level. (j) LEfSe cladogram. (k) LEfSe bar. Statistical differences between two groups were calculated by Student's t_-test with Welch's correction. ∗_P < 0.05 was regarded as statistically significant.

Figure 3

Figure 3

Dietary valine treatment changed the concentrations of short-chain fatty acids (SCFAs) in the cecum of laying hens and the correlation analysis between SCFAs and gut microbiota (n = 6). (a) The relative ratio of different SCFAs. (b) Total acid, acetic, propionic, butyric, isobutyric, valeric, and isovaleric acid. (c)–(e) Spearman correlation analysis between cecal microbiota at phylum, class, and order levels and SCFAs contents. Statistical differences between two groups were calculated by Student's t_-test with Welch's correction. A-BMeans with different superscripts within a column differ significantly (P < 0.05) or ∗_P < 0.05 was regarded as statistically significant.

Figure 4

Figure 4

mRNA expression levels of GCN2-related genes, inflammatory cytokines, and intestinal barrier in the jejunum of laying hens (n = 6 − 8). (a) GCN2. (b) eIF2_α_. (c) Atg5. (d) Atg7. (e) Caspase1. (f) IL-1_β_. (g) TNF-α. (h) Muc2. (i) Claudin-1. (j) ZO-1. (k) Occludin. A-BMeans with different superscripts within a column differ significantly (P < 0.05).

Figure 5

Figure 5

Effects of dietary valine supplementation on serum cytokines. (a) IL-6. (b) IL-10. (c) IL-12. (d) IL-1_β_. (e) IL-17. (f) TNF-α. (g) IFN-γ. A-DMeans with different superscripts within a column differ significantly (P < 0.05).

Figure 6

Figure 6

High levels of dietary valine treatment promoted liver steatosis of laying hens (n = 6). H&E: hematoxylin and eosin (100 ×). OA: oil red O (100 ×).

Figure 7

Figure 7

Effects of dietary valine treatment on serum and liver parameters changes (n = 6 − 8). (a) Serum TG. (b) Serum T-CHO. (c) Serum AST. (d) Serum ALT. (e) Liver TG. (f) Liver T-CHO. (g) Liver AST. (h) Serum ALT. A-BMeans with different superscripts within a column differ significantly (P < 0.05).

Figure 8

Figure 8

mRNA expression levels of GCN2 signaling ways, lipogenesis- and lipolysis-associated genes in the liver of laying hens (n = 6 − 8). (a) GCN2. (b) eIF2_α_. (c) ATF4. (d) ACC. (e) ACLY. (f) SCD1. (g) FASN. (h) PPAR_γ_. (i) SREBP-1c. (j) PPAR_α_. (k) CPT1. (l) ACOX1. A-CMeans with different superscripts within a column differ significantly (P < 0.05).

Figure 9

Figure 9

Effects of dietary valine treatment on antioxidase changes (n = 6 − 8). (a) Liver CAT. (b) Liver T-SOD. (c) Liver GSH-Px. (d) Serum GSH. (e) Serum GSSG. (f) Liver GSSG. (g) Liver T-AOC. (h) Liver MDA. (i) Liver GSH. A-BMeans with different superscripts within a column differ significantly (P < 0.05).

Figure 10

Figure 10

Effects of dietary valine treatment on liver cytokines (n = 6 − 8). (a) IL-6. (b) IL-10. (c) IL-12. (d) TNF-α. (e) IFN-γ. (f) IL-17. (g) IL-1_β_. A-BMeans with different superscripts within a column differ significantly (P < 0.05).

Figure 11

Figure 11

mRNA expression levels of ER stress-associated genes in the liver of laying hens (n = 6 − 8). (a) Cyt C. (b) GRP78. (c) CHOP. (d) Caspase 3. (e) Caspase 7. (f) Caspase 9. A-BMeans with different superscripts within a column differ significantly (P < 0.05).

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