Histidine and soy isoflavones co-ingestion induces browning of white adipose tissue and promotes lipolysis in female rats

Beige adipocytes arise from white adipocytes in response to cold or other stimuli, known as browning of white adipose. Beige adipocytes play a role similar to that of brown adipocytes, express high levels of uncoupling protein 1 (UCP1), and are responsible for energy consumption via heat production, thus aiding in fat loss. Although histidine (His) and soy isoflavones (Iso) co-ingestion reportedly reduces food intake, body weight, and fat accumulation in female rats, the underlying mechanism remains unclear. Therefore, this study aimed to elucidate the mechanisms whereby histidine and soy isoflavones (His-Iso) co-ingestion suppresses fat accumulation. Female rats were fed a control diet or diet containing Iso, His, or His-Iso for 2 weeks, followed by sampling of periovarian white adipose tissue (poWAT) and retroperitoneal white adipose tissue (rWAT) and adipocyte morphology analysis. Additionally, the expression of browning- and lipid metabolism-related genes was examined. Histochemical analysis revealed the presence of multilocular lipid droplets, representative of beige adipocytes, in the poWAT and rWAT of rats in the His-Iso co-ingestion group. Quantitative PCR analysis showed that His-Iso co-ingestion upregulated brown adipocyte and beige adipocyte markers, including UCP1, indicating that His-Iso intake induces beige adipocytes. Moreover, His-Iso co-ingestion upregulated genes related to fatty acid oxidation (carnitine palmitoyl transferase 1A) and lipolysis (adipose triglyceride lipase) in WATs. In conclusion, His-Iso co-ingestion increases UCP1 expression and morphological changes to beige adipocytes, and suppresses fat accumulation by promotion of lipolysis and fatty acid oxidation in WAT.