High-fat and high-sodium diet induces metabolic dysfunction in the absence of obesity

Objective: Excess dietary fat and sodium (NaCl) are both associated with obesity and metabolic dysfunction. In mice, high NaCl has been shown to block high-fat (HF) diet–induced weight gain. Here, the impact of an HF/NaCl diet on metabolic function in the absence of obesity was investigated. Methods: Wild-type mice were administered chow, NaCl (4%), HF, and HF/NaCl diets. Metabolic analysis was performed by measuring fasted blood glucose and insulin levels and by glucose tolerance test and insulin tolerance test. Results: After 10 weeks on diets, male and female mice on the HF diet gained weight, and HF/NaCl mice had significantly reduced weight gain similar to chow-fed mice. In the absence of obesity, HF/NaCl mice had significantly elevated fasting blood glucose and impaired glucose control during glucose tolerance tests. Both NaCl and HF/NaCl mice had decreased pancreas and β-cell mass. Administration of NaCl in drinking water did not protect mice from HF-diet-induced weight gain and obesity. Further analysis revealed that longer administration of HF/NaCl diets for 20 weeks resulted in significant weight gain and insulin resistance. Conclusions: The data demonstrate that despite early inhibitory effects on fat deposition and weight gain, an HF/NaCl diet does not prevent the metabolic consequences of HF diet consumption.