A high-carbohydrate diet-induced lipid deposition is alleviated by sodium pyruvate via suppression of the cPLA2-arachidonic acid-PPARγ axis.

BACKGROUND

Pyruvate is a critical node linking glycolysis and lipid metabolism. However, its regulatory role and mechanism in fish fed high-carbohydrate diets (HCD) remain obscure.

OBJECTIVES

In this study, we determined the role of sodium pyruvate (SP) in metabolic disorders induced by HCD and elucidated its underlying mechanisms using in vivo and in vitro models.

METHODS

All-male 4-mo-old AB strain zebrafish (Danio rerio) (0.356 ± 0.02 g) were fed a control diet, HCD, or HCD supplemented with 2% or 4% SP for four weeks (3 tanks/treatment, 30 fish/tank). Juvenile all-male 3-mo-old Nile tilapia (Oreochromis niloticus) (4.00 ± 0.19 g) were fed a control diet, HCD, or HCD with 1% or 2% SP for 8 wk (3 tanks/treatment, 30 fish/tank). Zebrafish liver cell line (ZFL) was treated with 10 mM glucose, 25 mM glucose, or 25 mM glucose plus 4 or 8 mM SP for 24 hours (n = 3).

RESULTS

Dietary SP reduced hepatic lipid accumulation in both species. In zebrafish, 4% SP reduced whole-body lipid content by 36.7% and hepatic triglyceride (TG) by 71.5% compared with HCD (P < 0.01). In Nile tilapia, 2% SP lowered liver total lipid by 21.8%, serum TG by 50.7%, and hepatosomatic index by 13.2% (P < 0.05). SP increased hepatic phospholipid content by 52.2% and hepatic superoxide dismutase activity by 21.0% (P < 0.05). In ZFL cells, 8 mM SP reduced intracellular TG by 59.2% compared with high-glucose treatment (P < 0.001). Mechanistically, SP downregulated cytosolic phospholipase A2 (cPLA2) expression, reduced arachidonic acid (AA) (by 24.0%) and 15-deoxy-Δ12,14-prostaglandin J2 (by 24.7%) levels, thereby suppressing peroxisome proliferator-activated receptor γ (PPARγ) signaling (P < 0.05).

CONCLUSION

This study demonstrates that dietary SP alleviates high-glucose-induced metabolic disorders via the cPLA2-AA-PPARγ axis, providing novel insights into optimising HCD utilisation in fish.