Insulin resistance and metabonomics analysis of fatty liver haemorrhagic syndrome in laying hens induced by a high-energy low-protein diet

Abstract

Fatty liver haemorrhagic syndrome (FLHS) is a widespread metabolic disease in laying hens that causes a decrease in egg production and even death. Insulin resistance is a major contributor to the pathogenesis of nonalcoholic fatty liver disease. However, the relationship between FLHS and the insulin resistance mechanisms underlying FLHS is not well elucidated. Therefore, we established an FLHS model induced by feeding a high-energy low-protein diet. In the current study, we found that the fasting glucose and insulin concentrations were elevated in the FLHS group compared with the control group during the experimental period. The results of the oral glucose tolerance test (OGTT) and insulin sensitivity test (IST) showed a high level of insulin resistance in the FLHS model. InsR, 4EBP-1, Glut-1 and Glut-3 mRNA expression were decreased, and TOR, S6K1, and FOXO1 were elevated ( P < 0.05 ). Metabolomic analysis with GC/MS identified 46 differentially expressed metabolites between these two groups, and of these, 14 kinds of metabolism molecules and 32 kinds of small metabolism molecules were decreased ( P < 0.05 ). Further investigation showed that glucose, lipid and amino acid metabolism blocks in the progression of FLHS by GO functional and pathway analysis. Overall, these results suggest that insulin resistance participated in FLHS; comprehensively, metabolites participated in the dysregulated biological process.

Osteocalcin prevents insulin resistance, hepatic inflammation, and activates autophagy associated with high-fat diet–induced fatty liver hemorrhagic syndrome in aged laying hens

“…In the present study, after fed 40 d of HFD, blood glucose tolerance, insulin sensitivity, and insulin concentration were decreased in hens, but these changes were alleviated by OCN administration. Similar to our results, Zhuang et al. (2019) reported that FLHS hens have higher blood glucose than the control hens detected by both OGTT and ITT.…”

“…Insulin is the only hyperglycemic hormone released by the pancreatic β cells in humans and various animals including chickens. Insulin resistance plays a key role in both human NAFLD and hen FLHS ( Gariani et al., 2013 ; Zhuang et al., 2019 ). In the present study, after fed 40 d of HFD, blood glucose tolerance, insulin sensitivity, and insulin concentration were decreased in hens, but these changes were alleviated by OCN administration.…”

“…Insulin resistance will lead to further hepatic damage by triggering oxidative stress and inflammatory reaction ( Gariani et al., 2013 ; Zhuang et al., 2019 ). Oxidative stress is caused by reactive oxygen compounds such as MDA which is a toxic molecule and has been used as an index of lipid peroxidation in humans and animals ( Czauderna et al., 2011 ; Konieczka et al., 2014 ; Du et al., 2016 ).…”

“…In addition, commercial hens have been selected for high production and feed efficiency, by which hen liver is more susceptible to metabolic disorder–induced injury. Hen FLHS has been used as a model of mammal nonalcoholic fatty liver disease ( NAFLD ) ( Ayala et al., 2009 ; Sanchez-Polo et al., 2015 ; Tsai et al., 2017 ; Wu et al., 2019 ; Zhuang et al., 2019 ). Although the pathophysiological mechanism of hen FLSH remains unclear, it could be similar to the ones identified in NAFLD, such as insulin resistance, hepatic oxidation stress, inflammatory reaction, and autophagy ( Ayala et al., 2009 ; Cai et al., 2011 ; Wu et al., 2019 ; Zhuang et al., 2019 ).…”

Serum Metabolomic Profiling to Reveal Potential Biomarkers for the Diagnosis of Fatty Liver Hemorrhagic Syndrome in Laying Hens

“…Related studies have shown that mannose can be used as a potential biomarker of insulin resistance ( Ferrannini et al, 2020 ). Our previous studies have also indicated that insulin resistance is highly correlated with the occurrence of FLHS in laying hens ( Zhuang et al, 2019 ). Regrettably, the results of this study showed that mannose levels decreased in the disease group at the two time points.…”