Abstract: Objective: To investigate the effect of Lacticaseibacillus paracasei N1115 combined with aerobic exercise on improving glucose and lipid metabolism, inflammatory response, learning and memory capacity, intestinal morphology and intestinal flora diversity in obese mice. Methods: C57BL/6 mice were used to establish an obese mouse model by feeding them a high-fat diet. Then, the mice were randomly divided into an obese control group, an aerobic exercise group, a probiotic intervention group, and a combined intervention group. Body mass, insulin resistance, liver fat content, intestinal tight junction protein expression, and intestinal microbial diversity were measured. The expression levels of inflammatory factors such as lipopolysaccharide (LPS), interleukin (IL)-6, IL-10, and nuclear factor kappa B (NF-κB) in the serum were detected by enzyme-linked immunosorbent assay (ELISA). Learning and memory capacity was assessed by using the Morris water maze test as well as measuring cyclic adenosine monophosphate (cAMP) content, and postsynaptic density protein-95 (PSD95) expression by Western blot. Results: Compared with obese mice, combined intervention with L. paracasei N1115 and aerobic exercise significantly reduced body mass (P < 0.05) and decreased fat accumulation by reducing the expression of sterol regulatory element binding protein-1 (SREBP-1)/fatty acid synthase. Besides, the combined intervention significantly reduced insulin tolerance in obese mice (P < 0.01), and alleviated the inflammatory response by reducing the expression levels of pro-inflammatory factors such as LPS, IL-6, and NF-κB (P < 0.01) and increasing the expression level of the anti-inflammatory factor IL-10 (P < 0.01). The combined intervention improved learning and memory capacity in obese mice by increasing the expression levels of the learning and memory factor cAMP (P < 0.01) and the cognitive function protein PSD95 (P < 0.01) in the serum. In addition, the intervention also improved gut microbiota diversity by reducing Firmicutes/Bacteroidetes ratio, and increasing ACE index, Chao1 index, and Shannon index and effectively alleviated the shedding of small intestinal villi. Conclusion: The combined intervention with L. paracasei N1115 and aerobic exercise reduce body mass and liver fat content in mice, alleviate inflammatory response, improve learning and memory capacity, and optimize intestinal morphology and gut microbiota composition.

Key words: Lacticaseibacillus paracasei; obesity; inflammatory factors; learning and memory; intestinal barrier