Metabolic and vascular adaptations to a positive energy balance

Since not all obese people develop insulin resistance and the time frame between the onset of obesity and the early onset of the disturbances in lipid, glucose and endothelium metabolism is not exactly known, longitudinal studies, studying the metabolic alterations in response to a positive energy balance in humans are needed.

The present study is a prospective study to evaluate the sequence of metabolic adaptations in lean subjects, during a positive energy balance followed by a negative energy balance.

A positive energy balance in male subjects with a first degree relative with DM II will result in a pro-inflammatory response (MCP-1, Il 6 and TNFá) associated with inflammatory changes within adipose tissue (AT) and an increased sympathetic activity. The degree of systemic and local (AT) inflammation will be predictive for the subsequent decrease in hepatic and peripheral insulin sensitivity. The negative energy balance will restore glucose and lipid metabolism to baseline levels preceded by a decrease in inflammatory markers.

This study will include 8 men who will consume a hyper caloric diet until they gain sufficient amount of weight, defined as 6% of their initial body weight. We expect that the study subjects will reach this target within 2-3 months. If participants have not reached the 6% weight gain within 3 months, the hypercaloric diet will be ended also. The hypercaloric diet will directly be followed by a hypo-caloric diet to return to the baseline weight.

Based on the eucaloric diet in the run-in phase, a hypercaloric diet will be designed calculated as 1.4 x kcal in the eucaloric diet. The protein, fat and carbohydrate content of the diet will respectively be 16%, 30% and 54% of the caloric intake. The surplus of energy will be provided as a liquid (Nutridrink) which consists of 12 g protein, 36.8 g carbohydrates and 11.2 g fat (total 300 kcal) per 200 ml. The hypercaloric diet will be ended when study subjects reach 6%weight gain, or after 3 months if participants do not have reached the 6% weight gain.

Thereafter based on the actual REE, the subjects will consume a diet (1.0 x REE) aimed to lose the gained weight and return to baseline weight. Subjects will be monitored weekly for resting energy expenditure, physical activity, weight, body composition and dietary intake. The diet will be adjusted if the weight remains stable. The study will be ended when the participant has lost the gained weight.