Succinic acid-driven gut-fat axis orchestrates abdominal fat deposition in chickens via adipocyte-macrophage crosstalk.

BACKGROUND: Excessive abdominal fat in broilers not only reduces feed efficiency and increases processing costs but also raises environmental concerns. This pathological overaccumulation results from complex metabolic dysregulation across multiple organs. While current research largely centers on adipogenesis within adipose tissue, a comprehensive understanding of the cross-organ regulatory factors influencing this process remains elusive. RESULTS: Here, we employed a high-fat diet (HFD) model and multi-omics approaches to investigate cross-organ regulatory mechanisms underlying abdominal fat deposition in broilers. Our results demonstrated that HFD not only promoted fat accumulation but also altered meat quality traits. Through 16S rRNA amplicon sequencing, we identified significant gut microbiota dysbiosis in HFD-fed chickens, manifested by an increased abundance of Lactobacillus and a decreased abundance of Enterococcus. However, jejunal microbiota transplantation from HFD donors did not induce abdominal fat deposition in recipient chickens. Metabolomic profiling revealed that HFD elevated the level of succinic acid, a metabolite positively correlated with Lactobacillus abundance and potentially generated by Lactobacillus. This increase in succinic acid (SA) further triggered metabolic inflammation response in both jejunal tissue and serum. In vivo validation established succinic acid as a key inflammatory mediator facilitating HFD-induced cross-organ communication between the jejunum and abdominal adipose tissue, enhancing intestinal lipid uptake and subsequent abdominal fat deposition. Bulk and single-nucleus RNA sequencing (snRNA-seq) revealed that HFD induced macrophage population expansion and intensified adipocyte-macrophage crosstalk. Adipocyte-macrophage co-culture systems further elucidated that macrophages are an indispensable factor in succinic acid-induced fat deposition. CONCLUSION: This study delineates a succinic acid-driven "gut-fat axis" governing abdominal fat deposition in broilers, integrating gut microbiota dysbiosis and macrophage-mediated inflammatory adipogenesis. By identifying succinic acid as a cross-organ signaling molecule that enhances lipid absorption and activates macrophage-dependent adipogenesis, we establish systemic metabolic-immune crosstalk as a pivotal regulatory mechanism. These findings redefine fat deposition as a process extending beyond adipose-centric models, advancing multi-omics-guided strategies for sustainable poultry production.