The pleiotropic metabolic effects of bariatric surgery.

In summary, unraveling the association between obesity and disturbances in lipid and glucose metabolism is necessary to improve future treatment modalities. The relationship between the increase in fat mass and the metabolic perturbations is complex and probably depends on the nature of the adaptive response to the hypercaloric milieu. The origin of these adaptations is most likely regulated centrally by several areas in the brain, including the hypothalamus, the prefrontal cortex and the satiety/rewarding centers of the brain. Differences in these adaptations may explain the different phenotypes of obesity in terms of disturbances in nutrient-related pathways. Therefore, studying adipose tissue biology and functional brain characteristics in the two extreme phenotypes of obesity (the metabolically healthy but obese vs. the metabollicaly abnormal and obese) will give insight in the role of adipose tissue and the brain in the switch from the metabolically healthy state to the unhealthy state.

Secondly, bariatric surgery is the only effective way to induce sustained weight loss and reversal of the obesity-induced changes in lipid and glucose metabolism.
Very early metabolic effects have been reported before the occurrence of weight loss, suggesting an acute effect of the surgery itself, i.e. bypassing the nutrient flow from the proximal gastrointestinal tract, on metabolism. Since the traditional factors known to be involved in glucose and metabolism do not change so quickly, other factors are involved. The current hypothesis is a reduced secretion of anti-incretin factors from the gut, but these factors have not been identified yet. An alternative explanation may be a quick central response, possibly mediated by this change in the incretin/anti-incretin balance, resulting in a centrally orchestrated amelioration of glucose and lipid metabolism.

1. The phenotypic difference between metabolically healthy but obese and metabolically unhealthy obese subjects is explained by:

a. differences in the neuroadaptation to the hypercaloric milieu, i.e. differences in dopamine receptor binding capacity in the area of the hypothalamus and striatal reward system, leading to differences in dopaminergic effects on insulin sensitivity and VLDL production

b. or structural differences within adipose tissue, with the main differences being related to inflammatory changes within adipose tissue.

2. The acute effects of malabsorptive bariatric surgery on glucose and lipid metabolism are mediated via (or associated with) changes of the activity pattern of the hypothalamus together with increased local striatal dopamine D2-receptor availability. This is accompanied by a near normalization of secretion of gut petides.

4 weeks pre-surgery

2-weeks post-surgery

5-weeks post-surgery

6-months post-surgery

Bariatric surgery