Food-grade Lactococcus lactis expressing LEK peptide ameliorates hypertension and hyperlipidemia via ACE inhibition and lipid metabolism regulation

Torreya grandis- derived peptide LEK is recognized for its potential to improve hypertension. However, its exact function and mechanism of action remain unknown. In addition, its widespread application is hindered by the high production costs and susceptibility to gastrointestinal digestion. To overcome these limitations, we developed an innovative approach using food-grade Lactococcus lactis as a delivery system to produce LEK peptide. The current study demonstrated that the LEK-deriving L. lactis significantly regulated hypertension in mice via ACE-related pathway. To our surprise, LEK-deriving L . lactis also significantly reduced serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels in high-fat diet mice, and improved hepatic lipid levels. Further investigation into the molecular mechanisms revealed that the engineered L . lactis could modulate the expression of key genes such as Pparg , Fasn , Cd36 , and Hmgcr . This study offers a novel solution for producing LEK peptide and their applications in the treatment of hyperlipidemia. • Construction of food-grade recombinant Lactococcus lactis with antihyperlipidemic effects. • Identification of digested peptides from recombinant L . lactis. • Systematic analysis of recombinant L . lactis safety. • Evaluation of the activity of engineered L . lactis in regulating hyperlipidemia and the underlying action mechanisms.