Threonine modulates the STAT3-SCD1 pathway to reduce fatty acid metabolism in duck hepatocytes.

Abstract

Dietary threonine (Thr) is known to influence fat deposition in poultry, but the precise mechanisms behind its regulatory effects on hepatic lipid metabolism remain elusive. Prior research indicated that including supplemental Thr in the feed may influence STAT3 (Signal Transducer and Activator of Transcription 3) levels in the liver of meat ducks. Numerous studies have recorded the function of STAT3 in regulating fatty acid (FA) metabolism in mammals. The primary objective of this study was to investigate whether Thr influences FA metabolism and triglycerides (TG) deposition in duck liver by regulating STAT3 expression. Primary hepatocytes were isolated from duck embryos and treated for 36 h with different doses of Thr (0, 10, 25, 50, 200 μM) in vitro or with a constructed STAT3 overexpression plasmid to examine the content of FAs and TG. RNA-seq was used to detect changes in gene expression in hepatocytes following STAT3 overexpression. The results demonstrated that both the exogenous addition of Thr and the overexpression of STAT3 significantly suppressed the capacity of hepatocytes for FAs deposition (P < 0.05). The overexpression of STAT3 also inhibited TG accumulation under conditions in response to Thr deficiency (P < 0.01). Transcriptomic analyses indicated that the overexpression of STAT3 inhibits the activity of triglyceride metabolism and unsaturated fatty acid biosynthesis (P < 0.01). Finally, a dual-luciferase reporter test demonstrated that STAT3 may systematically target and inhibit SCD1 transcription (P < 0.01). The present study indicates that supplemental Thr (50 μM) inhibits hepatic FA deposition via the STAT3-SCD1 pathway. This work enhances our comprehension of the functional roles of Thr and STAT3 in modulating lipid metabolism within duck livers. Moreover, it provides a partial theoretical foundation for the nutritional prevention and pharmacological intervention of lipid metabolism disorders in poultry.