Kaempferol attenuates diet-induced obesity and hepatic steatosis in C57BL/6J mice fed an Indian diet-mimicking regimen

Abstract

BACKGROUND

Metabolic dysfunction-associated steatotic liver disease (MASLD) ranges from simple steatosis to cirrhosis and liver cancer, with rising prevalence in India due to high fat, high sugar diets. Kaempferol, a generally recognized as safe-certified flavonoid found in fruits and vegetables with anti-inflammatory, antioxidant, and lipid-lowering properties. Despite its therapeutic promise, kaempferol’s efficacy remains unexplored in Indian diet-based obesity liver disease models. Developing such models could support targeted dietary interventions for the Indian population at elevated risk for MASLD progression.

AIM

To evaluate effect of kaempferol in C57BL/6J mice using an Indian diet-mimicking experimental animal model.

METHODS

Male C57BL/6J mice (6 weeks to 8 weeks, n = 3/group) were fed a normal diet or an Indian high fat diet (HFD) with fructose for 8.5 weeks, followed by kaempferol (50 mg/kg) or vitamin E (500 mg/kg) every other day for 4 weeks. Body weight, diet intake, liver function, and histopathology were evaluated. Liver samples were examined using hematoxylin and eosin staining. The non-alcoholic fatty liver disease score was assessed using the non-alcoholic steatohepatitis clinical research network criteria. The serum transforming growth factor beta 1 was detected using enzyme-linked immunosorbent assay kit. Additionally, the study also involves proximate and mineral composition of the diet for its validation. Moreover, the effect of kaempferol was further evaluated using an ex vivo precision-cut liver slice model.

RESULTS

We formulated a high calorie experimental HFD mimicking the Indian diet regimen (Indian HFD prepared and standardized in our lab and a provisional patent is filed), which shows an elevated crude fat and reduced crude fiber, ash, and moisture compared to the control feed. Mice fed this diet shows significant weight gain and hepatic steatosis, with macro-vesicular and micro-vesicular fat and lobular inflammation. Non-alcoholic fatty liver disease scoring confirms an increased steatosis and inflammation and also, transforming growth factor beta 1 levels were significantly elevated in the Indian HFD group. Kaempferol treatment significantly reduces body weight, steatosis, and inflammation. In ex vivo precision-cut liver slice models, kaempferol improved liver function enzymes and reduced hepatic triglycerides level.

CONCLUSION

Kaempferol improved hepatic steatosis and liver parameters in a diet-induced MASLD model mimicking the Indian diet, showing promising therapeutic potential.

Keywords: Metabolic dysfunction-associated steatotic liver disease; Indian high fat diet; High calorie diet; Natural product; Kaempferol; Hepatic steatosis

Core Tip: Metabolic dysfunction-associated steatotic liver disease spans from simple fat accumulation to cirrhosis and liver cancer, and its prevalence is steadily rising in India due to high fat, high sugar dietary habits. Kaempferol, a generally recognized as safe-approved flavonoid lipid-lowering effects, shows therapeutic potential but has not yet been evaluated in Indian diet-specific obesity driven liver disease models. This study demonstrates that kaempferol effectively attenuates diet-induced obesity and liver steatosis in C57BL/6J mice fed an Indian diet-mimicking regimen. The findings highlight kaempferol’s potential as a natural therapeutic agent for managing metabolic dysfunction and fatty liver disease associated with high calorie, region-specific dietary patterns.