The miR-216/miR-217 Cluster Regulates Lipid Metabolism in Laying Hens With Fatty Liver Syndrome via PPAR/SREBP Signaling Pathway

Abstract

Fatty liver syndrome (FLS), a common metabolic disease in laying hens, caused by excessive hepatic fat deposition is a bottleneck in the poultry industry. However, no specific therapeutic methods have been developed. Evidence suggests that microRNAs (miRNAs) are essential for liver lipid metabolism and homeostasis, providing strong evidence for targeting miRNAs as a potential treatment option for liver diseases. However, the roles of miRNAs in the pathogenesis of FLS remain unclear. In present study, RNA-sequencing was performed to discern the expression patterns of miRNAs in normal and fatty livers of laying hens. In total, 12 dysregulated miRNAs (2 down-regulated and 10 up-regulated) were detected between the normal and fatty livers. Functional enrichment analysis showed the potential impacts of the dysregulated miRNAs on lipid metabolism. Notably, miR-216a/b and miR-217-5p, which belong to the miR-216/miR-217 cluster, were up-regulated in the sera and livers of FLS chickens, as well as free fatty acid (FFA)-induced LMH cells. Oil-red O staining revealed that up-regulation of the miR-216/miR-217 cluster induced lipid accumulation in FFA-induced LMH cells. Furthermore, the dual luciferase gene reporter assay and RT-qPCR analysis demonstrated that 3-hydroxyacyl-CoA dehydratase 2, F-box protein 8, and transmembrane 9 superfamily member 3 (TM9SF3) were directly targeted by miR-216a/b and miR-217-5p, respectively, and suppressed in the fatty livers of laying hens. Moreover, overexpression of the miR-216/miR-217 cluster or reduction in TM9SF3 levels led to activation of the proliferator-activated receptor/sterol regulatory-element binding protein (PPAR/SREBP) pathway. Overall, these results demonstrate that the miR-216/miR-217 cluster regulates lipid metabolism in laying hens with FLS, which should prove helpful in the development of new interventional strategies.

Dietary naringin supplementation on hepatic yolk precursors formation and antioxidant capacity of Three-Yellow breeder hens during the late laying period

“…In avian, the yolk precursor formation and lipid metabolism depends on the regulation of E 2 and its downstream signal pathways ( Cui et al, 2020 ). Previous studies indicated that transcription levels of vitellogenins Ⅱ ( VTGⅡ ), apolipoprotein B ( ApoB ), apolipoprotein VLDL Ⅱ ( ApoVLDL Ⅱ ), sterol regulatory element binding transcription factor 1 ( SREBF1 ), diacylglycerol acyltransferase 2 ( DGAT2 ), fatty acid synthase ( FASN ), microsomal triglyceride transfer protein ( MTTP ), and peroxisome proliferator activated receptor alpha ( PPARα ) in liver tissues are positively correlated with lipid metabolism and egg yolk formation in hens ( Liu et al, 2016 ; Wang et al, 2016 ; Nii et al, 2020 ; Tolba et al, 2020 ; Zhu et al, 2022 ). Down-regulation of lipoprotein lipase ( LPL ) expression alleviates excessive lipid accumulation in liver tissues ( Beckford et al, 2017 ; Li et al, 2020 ).…”

Lactobacillus salivarius SNK-6 Regulates Liver Lipid Metabolism Partly via the miR-130a-5p/MBOAT2 Pathway in a NAFLD Model of Laying Hens

“…Liver samples were embedded in Tissue-Tek OCT embedding compound, frozen on dry ice, cut into 8-μm-thick frozen sections, and stained with an Oil Red Staining kit (Solarbio, Beijing, China). LMH cells were cultured with 1 mM free FAs (FFAs), as we described previously [ 21 ], and a 10-fold dilution of L. salivarius SNK-6 medium supernatant was added and incubated for 24 h. Cells were collected and fixed in 4% paraformaldehyde, stained by Oil Red O Staining kit (Solarbio), and observed under an electron microscope (Nikon). Data were analyzed by Image-Pro Plus 6.0 software.…”

MiRNAs in Alcohol-Related Liver Diseases and Hepatocellular Carcinoma: A Step toward New Therapeutic Approaches?

“…SREBP is a major transcription factor transactivating lipogenesis-related genes (e.g., FASN, ACACA) [118], and its regulation by microRNAs has been extensively documented in the context of NAFLD [119,120]. As described above, the downregulation of miR-203 expression in the liver of mice fed an alcoholic diet [37], is directly responsible for the upregulation of Lipin-1 [37], which can promote β-oxidation and inhibit SREBP-1 signaling.…”