Impact of short-term high-fat overnutrition on glucose metabolism and gut permeability

Introduction: Excessive consumption of high-energy/high-fat diets together with lack of physical activity is considered to cause obesity, associated with low grade inflammation and insulin resistance, and may also induce gut barrier dysfunction. The purpose of this study was to assess whether seven days of overnutrition increase inflammatory load and impair gut permeability and insulin sensitivity.

Methods: 24 men (BMI 23.0 ± 2.1 kg/m²) underwent a 7 d-overfeeding programme including an excess energy intake of 1,000 kcal above the individually calculated energy expenditure. Anthropometric and clinical characteristics were assessed and insulin sensitivity and gut permeability were measured before and after intervention. Insulin sensitivity was determined using the hyperinsulinemic euglycemic clamp technique. Gut permeability was measured by a standardized four-sugar-test (mannitol, lactulose, sucrose, sucralose), a polyethylene glycol test, and determination of plasma zonulin.

Results: Seven days of highly standardized overnutrition resulted in a mean body weight gain of 0.9 ± 0.62 kg. However, seven days of energy surplus did not result in an increase of the inflammatory parameters hsCRP, leptin, and MCP-1. Mean urinary excretion of the four sugars and polyethylene glycol also did not change significantly after seven days of the high-fat, high caloric diet and zonulin as well. Despite a body weight increase in the expected range, both the M-value and glucose disposal during clamp before and after the intervention did not produce any significant change.

Conclusion: Our findings do not provide evidence that one week overfeeding with 1,000 kcal surplus would significantly affect either insulin sensitivity or gut permeability in healthy normal-weight men.