Free amino-acid and imidazole-ring dipeptide profiles of chicken-liver-hydrolysate supplement and its modulatory effects on lipid metabolism, oxidative status, and inflammation in livers, as well as gut microbiota in a high-fat diet.

Chicken livers can be sustainably developed into nutraceuticals through the circular-agriculture innovation chain. A supplement (GBHP01) formulated from chicken-liver hydrolysates contains free-type hypolipidemic amino acids (threonine, valine, leucine, isoleucine, and taurine) and the imidazole-ring dipeptide (anserine). In this study, mice were assigned to four groups: (1) Control: control diet (AIN-93M formula; fat providing 9.4% of total calories), (2) HFD: high-fat diet (fat providing 46.5% of total calories), (3) GBHP01.L: HFD supplemented with GBHP01 at 133.61 mg/Kg BW/day, and (4) GBHP01.H: HFD supplemented with GBHP01 at 267.22 mg/Kg BW/day. GBHP01 was administered by oral gavage. In 20-week HFD feeding, GBHP01 supplementation significantly reduced serum lipids, ALT, AST, and hepatic tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) concentrations, while enhancing reduced GSH, TEAC, catalase, and GSH-Px levels (p<0.05). Histological analysis revealed decreased hepatic lipid accumulation, associated with decreased diacylglycerol O-acyltransferase 2 (DGAT2) and increased acyl-CoA dehydrogenase medium chain (ACADM) expression. GBHP01 also promoted fecal bile acid and triglyceride excretion, indicating reduced fat absorption. Fecal microbiota profiling showed that HFD disrupted microbial diversity, increasing detrimental genera (Desulfovibrio, Bilophila, and Lachnoclostridium) while decreasing beneficial taxa (Lactobacillus and Akkermansia). GBHP01 may contribute to shifts in gut microbial composition by elevating probiotic species (L. reuteri and L. murinus) and reducing inflammatory taxa (Bilophila and Mucispirillum), suggesting its potential as a dietary intervention against HFD-induced metabolic disorders.