Fatty liver hemorrhagic syndrome (FLHS) is a metabolic condition of chicken and other birds caused by diverse nutritional, hormonal, environmental, and metabolic factors. Here we studied the effect of different diet composition on the induction of FLHS in single comb White Leghorn (WL) Hy-line laying hens. Seventy six (76) young WL (26 wks old) laying hens and 69 old hens (84 wks old) of the same breed were each divided into 4 treatment groups and provided 4 different diet treatments. The diet treatments included: control (C), 17.5% CP, 3.5% fat (F); normal protein, high fat (HF), 17.5% CP, 7% F; low protein, normal fat (LP), 13% CP, 3.5% F; and low protein, high fat (LPHF), 13% CP, 6.5% F. The diets containing high fat also had a higher ME of 3,000 kcal/kg of feed while the other 2 diets with normal fat had a regular lower amount of ME (2750 kcal/kg). Hen-day egg production (HDEP), ADFI, BW, egg weight, plasma enzymes indicating liver damage (alkaline phosphatase [ALP], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT]), liver and abdominal fat weight, liver color score (LCS), liver hemorrhagic score (LHS), liver fat content (LFC), liver histological examination, lipid peroxidation product in the liver, and genes indicating liver inflammation were evaluated. HDEP, ADFI, BW, and egg weight were significantly decreased in the LPHF diet group, while egg weight was also decreased in the LP diet group. In the young hens (LPHF group), ALP was found significantly higher at 30 d of diet treatment and was numerically higher throughout the experiment, while AST was significantly higher at 105 d of treatment. LCS, LHS, and LFC were significantly higher in young hens on the LPHF diet treatment. A liver histological examination shows more lipid vacuolization in the LPHF treatment diet. HF or LP alone had no significant effect on LFC, LHS, or LCS. We suggest that LP in the diet with higher ME from fat can be a possible natural cause for predisposing laying hens to FLHS.

Cholesterol is the only lipid whose absorption in the gastrointestinal tract is limited by gate‐keeping transporters and efflux mechanisms, preventing its rapid absorption and accumulation in the liver and blood vessels. In this review, I explored the current data regarding cholesterol accumulation in liver cells and key mechanisms in cholesterol‐induced fatty liver disease associated with the activation of deleterious hypoxic and nitric oxide signal transduction pathways. Although nonalcoholic fatty liver disease (NAFLD) affects both obese and nonobese individuals, the mechanism of NAFLD progression in lean individuals with healthy metabolism is puzzling. Lean NAFLD individuals exhibit normal metabolic responses, implying that liver damage is not associated with impaired metabolism per se and that direct lipotoxic effects are crucial for disease progression. Several redox and oxidant signaling pathways involving cholesterol are at play in fatty liver disease development. These include impairment of the mitochondrial and lysosomal function by cholesterol loading of the inner‐cell membranes; formation of cholesterol crystals and hepatocyte degradation; and crown‐like structures surrounding degrading hepatocytes, activating Kupffer cells, and evoking inflammation. The current review focuses on the induction of liver inflammation, fibrosis, and steatosis by free cholesterol via the hypoxia‐inducible factor 1α(HIF‐1α), a main oxygen‐sensing transcription factor involved in all stages of NAFLD. Cholesterol loading in hepatocytes can result in chronic HIF‐1αactivity because of the decreased oxygen availability and excessive production of nitric oxide and mitochondrial reactive oxygen species.

High-fat diet (HFD) leads to enhancement in various parameters of mice like weight, fasting glucose levels, adipose tissue, and also the liver weight in male C57 BL/6 J mice. Additionally, high-fat diet causes severe liver damage with significant increase in the level of aspartate amino transferase (AST) and alanine transaminase (ALT). The variations in microbiota induced by different diet were analyzed by Illumina MiSeq platform with sequencing of 16S ribosomal RNA (rRNA) gene, and QIIME pipeline was used. The population of Proteobacteria was found to be higher in HFD cecum sample as compared to other treatments. Microbiota analysis suggests that phylum Proteobacteria and Firmicutes were found to be higher in high-fat diet groups as compared to mice fed with normal diet (ND). At the genus level, Bacteroides showed higher population in HFD diet. Bacterial strains belonging to Enterobacteriaceae like Escherichia, Klebsiella, and Shigella were also dominant in HFD treatments. Furthermore, we explored the effects of ethanol production in vitro with supplementation of dietary fibers following inoculation of ND and HFD microbiotas. HFD microbiota of cecum and feces showed high level (P < 0.05) of ethanol production with 2% fructooligosaccharide (FOS) as compared to 2% galactomannan. Microbial fermentation also generated short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate. High levels (P < 0.05) of propionate were found after fermentation of FOS with HFD cecum and feces microbiota. The present study highlights the HFD-induced population of phylum Proteobacteria and genus Bacteroides for ethanol production using FOS as a dietary supplement, and these findings may imply on the harmful effect of HFD even at the microbiota level.

Background: Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are associated with increased oxidative stress and lipid peroxidation, but large studies are lacking. The aim was to test the association of malondialdehyde (MDA), as a marker of oxidative damage of lipids, with NAFLD and liver damage markers, and to test the association between dietary vitamins E and C intake and MDA levels. Methods: A cross-sectional study was carried out among subjects who underwent blood tests including FibroMax for non-invasive assessment of NASH and fibrosis. MDA was evaluated by reaction with Thiobarbituric acid and HPLC-fluorescence detection method. NAFLD was diagnosed by abdominal ultrasound. Findings: MDA measurements were available for 394 subjects. In multivariate analysis, the odds for NAFLD were higher with the rise of MDA levels in a dose–response manner, adjusting for age, gender, BMI, and lifestyle factors. Only among men, higher serum MDA was associated of higher odds for NAFLD and NASH and/or fibrosis (OR = 2.59, 95% CI 1.33–5.07, P = 0.005; OR = 2.04, 1.02–4.06, P = 0.043, respectively). Higher vitamin E intake was associated with lower odds of high serum MDA level (OR = 0.28 95% CI 0.13–0.62, P = 0.002). In conclusion, serum MDA is associated with NAFLD and markers of NASH or fibrosis among men. Dietary vitamin E may be protective among women.