Effect of a hypercaloric diet on brain insulin sensitivity and liver fat
in normal-weight men
S. Kullmann Diabetologia (2021) 64 (Suppl 1):S1–S380
Background and aims: Obesity and prediabetes are associated with
brain insulin resistance with unfavorable effects on long-term weight
and body fat composition. Whether short-term overfeeding can trigger
brain insulin resistance in healthy humans is currently not known. Hence,
we investigated the effect of a five-day hypercaloric diet on brain insulin
responsiveness and body fat composition in healthy normal weight adults.
Materials and methods: Twenty-nine male volunteers (age range 19 - 27
years, BMI range 19 - 25 kg/m2 ) were enrolled to participate either in a
five-day hypercaloric diet (n= 18; increasing their daily caloric intake by
1500 kcal with high caloric snacks) or a control diet (n=11; no additional
calories). Brain insulin sensitivity was assessed by functional magnetic
resonance imaging (MRI) combined with intranasal administration of
insulin to the brain before, directly after the hypercaloric diet and 2 weeks
afterwards. Food intake and physical activity was recorded during the
course of the study. Moreover, participants underwent two oral glucose
tolerance tests, whole-body MRI for body fat distribution/ intrahepatic fat
content and different behavioral and cognitive assessments.
Results: Paired t-test in the five-day hypercaloric diet group revealed
a significant change in brain insulin action in the insular cortex from
before to directly after the intervention (p<0.05, corrected for multiple comparisons). Two weeks after the diet, brain insulin action was
restored. No change in brain insulin action was observed in the
control group (n=11). Moreover, intrahepatic fat significantly
increased in the intervention group directly after the five-day
hypercaloric intervention (mean change of 53%; p=0.001), while no
change was observed in the control group (mean change of 3%;
p=0.673). High-caloric diet induced alterations in brain insulin
responsiveness significantly correlated with increased liver fat (r=
0.606, p=0.001). No significant effects were observed on glucose
metabolism, peripheral insulin sensitivity and body weight. To
compare our results to a normal weight and obese control group
without an intervention, we extracted the insular cortex response to
intranasal insulin in twenty-nine age-matched participants from a
previous study cohort. Interestingly, brain insulin action in the insula
of the obese control group showed a similar response to intranasal
insulin, as we observed in the current study after the high caloric diet.
The normal weight control group, on the other hand, showed a
response just as in our current study before the intervention.
Conclusion: In normal weight men, short-term overfeeding with high
caloric snacks can trigger brain insulin resistance and liver fat accumulation. Brain insulin action after overfeeding was similar as observed in agematched persons with obesity