In ovo injection of betaine alleviates corticosterone-induced fatty liver in chickens through epigenetic modifications

Abstract

Betaine alleviates high-fat diet-induced fatty liver and prenatal betaine programs offspring hepatic lipid metabolism. Excessive corticosterone (CORT) exposure causes fatty liver in chickens, yet it remains unknown whether and how prenatal betaine modulates the susceptibility of CORT-induced fatty liver later in life. In this study, fertilized eggs were injected with saline or betaine before incubation, and the hatchlings were raised at 8 weeks of age followed by 7 days of subcutaneous CORT injection. CORT-induced fatty liver was less severe in betaine-treated chickens, with significantly reduced oil-red staining and hepatic triglyceride content (P < 0.05). The protective effect of prenatal betaine was associated with significantly up-regulated expression of PPARα and CPT1α, as well as mitochondrial DNA (mtDNA)-encoded genes (P < 0.05). Moreover, betaine rescued CORT-induced alterations in methionine cycle genes, which coincided with modifications of CpG methylation on CPT1α gene promoter and mtDNA D-loop regions. Furthermore, the elevation of hepatic GR protein content after CORT treatment was significantly reduced (P < 0.05), while the reduction of GR binding to the control region of affected genes was significantly increased (P < 0.05), in betaine-treated chickens. These results indicate that in ovo betaine injection protects the juvenile chickens from CORT-induced fatty liver.

Probiotics Supplementation Alleviate Corticosterone-induced Fatty Liver Disease Related With the Changes of Hepatic Lipogenesis and Gut Microbiota Profile in Broiler

“…The signi cant increase of TG concentration in plasma and liver, as well as histological features including steatosis and vacuolar degeneration by CORT injection in the present study was in accordance with our previous work in chickens subjected to exogenous CORT exposure [9] and in rats exposed to dexamethasone(DEX)challenge [27]. Interestingly, our results clearly showed that these phenotypic characterizations of fatty liver disease in broilers was greatly ameliorated by administration of probiotics mixture administration.…”

“…Previous study indicated that hepatic fat deposition in NAFLD patients mainly attributed to the highly regulated metabolic pathway for the synthesis of fatty acids from ACC [30]. Consistently, the fatty liver disease caused by exogenous glucocorticoids exposure was mainly resulted from the activation of lipogenesis in chickens [9] as well as in rats [27]. In this study, our results indicated that the mRNA expression levels of ACC, the key rate-limiting enzyme of de novo lipogenesis, and SREBP-1, a key transcription factor of downstream of ACC, in the chicken liver were increased by CORT challenge.…”

“…Glucocorticoid hormones (GCs) are important regulators of lipid metabolism, promoting lipogenesis when treated with chronic exposure [5].For instance, chronic excessive GCs exposure induced whole-body insulin resistance, strongly related to metabolic dysfunction including intrahepatic lipid accumulation, intramuscular fat deposition and abdominal adiposity in humans [6,7].Corticosterone (CORT) is the main active form of GC in chickens. Previous studies have shown that fatty liver disease can be induced by excessive CORT exposure in broilers [8][9][10].…”

Hepatic Inflammatory Response to Exogenous LPS Challenge is Exacerbated in Broilers with Fatty Liver Disease

“…Birds in the CON and LPS groups received vehicle treatment through daily subcutaneous injection of solvent (15% ethanol). Birds in the CORT and LPS&CORT groups received, for one week, CORT treatment (4.0 mg/kg) through daily (9:00-10:30 and 16:00-17:30) subcutaneous injections [10]. Corticosterone (C2505, Sigma-Aldrich, USA) was dissolved in 15% ethanol, and LPS (L2880, Sigma-Aldrich, St. Louis, MO, USA) was dissolved in saline.…”

“…The active form of GC in chickens is primarily corticosterone (CORT), an indicator of stress [8]. Moreover, it is well known that treatment with exogenous CORT can cause abnormal fat deposition in the liver [9,10].…”