Curcumin-Rich Diet Mitigates Non-Alcoholic Fatty Liver Disease (NAFLD) by Attenuating Fat Accumulation and Improving Insulin Sensitivity in Aged Female Mice under Nutritional Stress

Abstract

Background: The high incidence of metabolic syndrome in the elderly poses a significant challenge to the healthcare system, emphasizing the need for interventions tailored to geriatric patients. Given the limited focus on females in previous studies, this research aimed to evaluate the effects of dietary curcumin on obesity and NAFLD outcomes in naturally aged (18-month-old) female mice. Methods: Female C57BL/6 mice aged 18 months were fed a normal chow diet (NCD) and a HFHSD, with or without curcumin (0.4% w/w), for an 8-week period. Parameters included food intake, body weight, insulin tolerance test (ITT), glucose tolerance test (GTT), percentage fat mass, hepatic triglyceride, and cholesterol levels, and a histological examination for NAFLD detection, qPCR, and immunoblotting analyses were performed. Results: The cumulative body weight gain after 8 weeks in the aged female mice supplemented with curcumin and fed an HFHSD was significantly lower (10.84 ± 1.09 g) compared to those fed a HFHSD alone (15.28 ± 1.26 g). Curcumin supplementation also resulted in reduced total body fat (HFHSD group 50.83 ± 1.71% vs. HFHSD+CUR 41.46 ± 3.21%), decreased epidydimal fat mass (HFHSD: 3.79 ± 0.29 g vs. HFHSD+CUR: 2.66 ± 0.30 g), and repaired adipogenic signaling in the white adipose tissue. Furthermore, curcumin lowered triglyceride and cholesterol deposition in the liver, preventing hepatic steatosis and improving hepatic insulin sensitivity. Conclusions: Curcumin demonstrates the ability to ameliorate the deleterious effects of HFHSD in aged female mice by reducing body fat composition, modulating adipogenic signaling in the white adipose tissue, and improving insulin homeostasis and non-alcoholic fatty deposition in the liver.