Cholesterol lowering and anti-obesity effects by the combination of heat-treated lactobacillus KDP and guar gum in mice fed a high-fat diet

Objectives: KDP, heat-treated Lactobacillus sakei is expected to function as paraprobiotics. Guar gum, a soluble fiber obtained from guar bean, has prebiotic properties. We found that the combination of paraprobiotics and prebiotics synergistically alleviated obesity and cholesterol levels, but the mechanism is unknown. Therefore, we conducted experiments to elucidate the mechanism by which the ingestion of heat-treated KDP alone and the combined ingestion of KDP and guar gum lowers cholesterol in high-fat diet-induced obese mice. Methods: Six-week-old male C57BL/6J mice were divided into 5 groups: standard diet (ST), high-fat diet (HF), 5% guar gum + high-fat diet (Guar), 0.1% KDP + high-fat diet (KDP), and 5% guar gum + 0.1% KDP + high-fat diet (Mix) for 16 weeks. Water and feed were consumed ad libitum. At 16 weeks of rearing, the mices were dissected, and their organs were harvested for analysis. Gene expression analysis related to lipid metabolism in adipose tissue and cholesterol metabolism in liver were conducted. Results: Perirenal adipose tissue showed a significant decrease in the Mix group compared to the HF group. Lipid metabolism-related gene (PPARγ, GPR43, Fasn, Acaca) expression tended to increase in PPARγ and GPR43 in the Mix group. Mix diet may improve of lipid metabolism. Furthermore, total cholesterol levels were significantly lower in the Mix group than in the HF group. Expression analysis of cholesterol metabolism-related genes (ABCG5, ABCG8, BSEP, ABCC2, HMGCR, Cyp7α1, and LDLr) in the liver was conducted. Cyp7α1, HMGCR, and LDLr expressions were decreased in the Mix group compared to HF group. This result suggests that cholesterol lowing effect of Mix may be involved in the inhibition of cholesterol synthesis. Conclusion: Combined consumption of heat-treated KDP and guar gum significantly reduced perirenal adipose tissue weight and total cholesterol levels in high-fat diet-induced obese mice by improving lipid metabolism and inhibition of cholesterol synthesis.