Dietary Blueberry Supplementation Attenuates the Effects of an Ultra-Processed Food Cafeteria Diet on Weight Gain and Metabolic Parameters, Enhancing Nutrigenomic Profiles in C57BL/6 Mice.

The cafeteria diet (CAFD) model mimics Western dietary patterns, inducing obesity in mice. Blueberry (BB) consumption improves metabolic outcomes due to its anti-inflammatory and antioxidant properties, though mechanisms remain unclear. This study assessed BB supplementation effects on biometric, metabolic, and hepatic steatosis parameters in CAFD-fed mice, and analyzed obesity-related gene expression in adipose tissues, liver, muscle, and hypothalamus. Thirty-two male C57BL/6 mice were divided into three groups: Control (C, standard diet-SD; N = 10), CAF (CAFD + SD; N = 12), and BB (SD + CAFD + BB; N = 10). BB animals received 22.4 g of freeze-dried BB per week. After 16 weeks, biometric and glycemic parameters, insulin resistance (IR), hepatic steatosis, oxidative stress markers, and serum leptin, adiponectin, and irisin levels were evaluated. Expression of genes related to apoptosis, lipid and glucose metabolism, oxidative stress, and adipocytokine pathways was analyzed by qPCR. BB supplementation improved biometric, glycemic, IR, hepatic steatosis, and oxidative stress and antioxidant markers compared to CAF. Leptin, adiponectin, and irisin levels decreased in BB mice. Also, BB consumption modulated the expression of obesity-related genes. BB mitigated CAFD-induced weight gain, IR, hepatic steatosis, oxidative stress, and obesity-related gene dysregulation, highlighting its nutrigenomic potential.