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PubMed2025

Genomic insights into the demographic history and local adaptation of wild boars across Eurasia.

Wild boars exhibit genetic and phenotypic diversity shaped by migrations and local adaptations. Their expansion across Eurasia, especially in Central Asia, remains underexplored. Here, we present newly sequenced whole-genome data of 47 wild boars from Eastern Asia, Central Asia, and Europe, combined with 49 existing genomes, creating a comprehensive dataset of 96 individuals. Our analyses show that Asian wild boars and Southeast Asian Suids split ∼3.6 million years ago (mya), with Central Asian and Southern Chinese ancestors diverging ∼1.8 mya. The split between Central Asian and European-Near East ancestors occurred ∼0.9 mya, followed by a European-Near East divergence ∼0.6 mya. We identify signatures of local adaptation in Central Asian populations, including two positively selected variants in LPIN1, associated with lipid metabolism, and a missense mutation in ALPK2, linked to meat traits. These findings provide insights into wild boar dispersal and adaptation and shed light on domestic pig breeding.

Animals↗
PubMed2026

Conditional eIF2A Deletion Suggests Extra-Adipose Mechanisms Underlying Metabolic Syndrome in Total-Body eIF2A Knockout Mice.

Dynamic regulation of protein synthesis is essential for metabolic homeostasis, with translation initiation playing a key role in this process. Emerging evidence strongly indicates that in addition to canonical eukaryotic initiation factors (e.g., eIF2, eIF4E) non-canonical factors, such as eukaryotic initiation factor 2A can modulate metabolic homeostasis. eIF2A is a highly conserved eukaryotic protein originally proposed to function analogously to bacterial IF2, promoting initiator Met-tRNAi recruitment to the 40S ribosomal subunit, though its precise mechanism remains debated. To investigate its organismal role, we have previously generated the total-body eIF2A knockout mouse, which revealed eIF2A functions in lipid homeostasis, glucose tolerance, insulin sensitivity, and susceptibility to metabolic syndrome. To further determine whether adipose tissue drives these phenotypes, we presently generated adipose-specific eIF2A knockout mice. Despite dysregulation of some key adipokines, including for example, adiponectin, these mice did not develop metabolic syndrome, even under high-fat diet conditions, indicating that adipose tissue specific deficiency of eIF2A is insufficient to reproduce the metabolic defects observed in total-body knockout. However, we found that eIF2A deficiency in the liver of the total body eIF2A-KO mice can independently drive metabolic syndrome components via translational control of Lpin1 (a phosphatidate phosphatase and a transcriptional coactivator) that controls hepatic lipid storage and metabolism. eIF2A deficiency in the liver leads to disruption of fatty acid oxidation and the production of ketone bodies, not observed in adipose-specific eIF2A knockout mice. Our findings suggest that systemic metabolic effects observed in the total body eIF2A-KO mice may arise from coordinated functions across multiple organs.

adipose tissue↗
PubMed2025

Silencing FAF2 mitigates alcohol-induced hepatic steatosis by modulating lipolysis and PCSK9 pathway.

BACKGROUND: Chronic alcohol consumption leads to lipid accumulation, oxidative stress, cellular damage, and inflammation in the liver, collectively referred to as alcohol-associated liver disease (ALD). FAF2/UBXD8/ETEA (Fas-associated factor 2) is a ubiquitin ligase adaptor protein that plays a crucial role in the ubiquitin-mediated degradation of misfolded proteins in the endoplasmic reticulum. A recent genome-wide association study indicated an association between FAF2 and ALD; however, the exact contribution of FAF2 to ALD pathogenesis remains unclear. METHODS: FAF2 was knocked down using AAV-delivered shRNA in C57/BL6 mice. Mice were subjected to a chronic-plus-single binge ethanol feeding (NIAAA) model. Nine hours after gavage, liver, blood, and other organs of interest were collected for gene expression and biochemical analyses. RESULTS: We first observed a significant elevation in hepatic FAF2 protein expression in individuals with ALD and in mice subjected to an ethanol-binge model. Interestingly, knocking down FAF2 in the liver using adeno-associated virus serotype 8-delivered short hairpin RNA conferred a protective effect against alcohol-induced liver steatosis in ethanol-binged mice. Transcriptomic analysis revealed that differentially expressed genes were enriched in multiple lipid metabolism regulation pathways. Further analysis of transcription factors regulating these differentially expressed genes suggested potential regulation by SREBP1. Several SREBP1 target genes, including Fasn, Scd1, Lpin1, and Pcsk9 (proprotein convertase subtilisin/kexin type 9), were dysregulated in the livers of ethanol-fed FAF2 knockdown mice. Additionally, Pcsk9 could be regulated through the FOXO3-SIRT6 pathway in the livers of ethanol-fed FAF2 knockdown mice, leading to increased liver low-density lipoprotein receptor expression and reduced plasma LDL cholesterol levels. Furthermore, FAF2 knockdown in mouse liver enhanced adipose triglyceride lipase lipolytic activity by upregulating the adipose triglyceride lipase activator, comparative gene identification-58, and downregulating the adipose triglyceridelipase transport inhibitor, Elmod2, contributing to the alleviation of liver steatosis. CONCLUSIONS: Our study uncovers a novel mechanism involving FAF2 in the pathogenesis of ALD.

Animals↗