Evidence for a relationship between body mass and energy metabolism in the human brain

Abstract

Cerebral energy metabolism has been suggested to have an important function in body weight regulation. We therefore examined whether there is a relationship between body mass and adenosine triphosphate (ATP) metabolism in the human brain. On the basis of our earlier findings indicating a neuroprotective preferential energy supply of the brain, as compared with peripheral muscle on experimentally induced hypoglycemia, we examined whether this physiological response is preserved also in low-weight and obese participants. We included 45 healthy male subjects with a body mass index (BMI) ranging from 17 to 44 kg/m(2). Each participant underwent a hypoglycemic glucose-clamp intervention, and the ATP metabolism, that is, the content of high-energy phosphates phosphocreatine (PCr) and ATP, was measured repeatedly by (31)phosphor magnetic resonance spectroscopy ((31)P-MRS) in the cerebral cortex and skeletal muscle. Results show an inverse correlation between BMI and high-energy phosphate content in the brain (P<0.01), whereas there was no such relationship found between skeletal muscle and BMI. The hypoglycemic clamp intervention did not affect the ATP metabolism in both tissues. Our data show an inverse correlation between BMI and cerebral high-energy phosphate content in healthy humans, suggesting a close relationship between energetic supply of the brain and body weight regulation.

Figure 1

Mean values±s.e.m. of blood glucose during glucose-clamp experiments. There was no difference in circulating glucose concentrations between low-weight (black triangles), normal-weight (white circles), and obese (black circles) subjects throughout the study (n=15 in each group). Arrows mark the time points of ³¹phosphor magnetic resonance spectroscopy measurements. Small panel: mean values±s.e.m. of serum insulin concentrations during the experiments. Overall, insulin levels were higher in obese participants as compared with both normal-weight and low-weight subjects (P<0.001).

Figure 2

Mean values±s.e.m. of cerebral high-energy phosphates. Phosphocreatine (A) and adenosine triphosphate (ATP; α- + β- + γ-ATP/3) (B) content in low-weight (black triangles), normal-weight (white circles), and obese (black circles) subjects are shown at baseline, during the glycemic decrease, and at the hypoglycemic plateau (n=15 in each group). As values are determined by calculating the area under the spectral peak, no units are indicated. Gray areas mark the hypoglycemic period; asterisks mark significant analyses of variance group effects (^*P<0.05; ^**P<0.01; ^***P<0.001).

Figure 3

Correlation analyses between body mass index (BMI) and baseline phosphocreatine (A) and adenosine triphosphate (ATP; α- + β- + γ-ATP/3) (B) levels in the brain including all participants (n=45). Both measures indicate the same pattern. BMI correlates inversely with cerebral high-energy phosphate content. As phosphate values are determined by calculating the area under the spectral peak, no units are indicated.