Protective effect and mechanism of lactoferrin combined with hypoxia against high-fat diet induced obesity and non-alcoholic fatty liver disease in mice

Obesity is a global epidemic, it can induce glucose and lipid metabolism disorder and non-alcoholic fatty liver disease (NAFLD). This study explored a new way to control weight and improve fatty liver, namely, living in hypoxia environment and supplement with lactoferrin (Lf). Sixty male C57BL/6J mice were divided into six groups, namely, control, hypoxia, high-fat diet, hypoxia + high-fat diet, hypoxia + high-fat diet + low dose Lf intervention, and hypoxia + high-fat diet + high-dose Lf intervention. Mice in the hypoxia treatment groups were treated with approximately 11.5 % oxygen for 6 h every day for 8 weeks. Results showed that interventions combining Lf and hypoxia treatments showed better effect against obesity and NAFLD than hypoxia treatment alone. The interventions controlled weight gain in mice, improved glucolipid metabolism in mice. The combination intervention reduced cholesterol absorption by reducing the level of hydrophobic bile acids, and elevating the level of hydrophilic bile acids. Gut microbiota analysis revealed that the combination intervention considerably elevated short chain fatty acids (SCFAs)-producing bacteria level, and reduced the Desulfovibrionaceae_unclassified level. Thus, Lf combined with hypoxia intervention effectively prevents obesity and NAFLD by restoring gut microbiota composition and bile acid profile.