Exp Clin Endocrinol Diabetes 2014; 122 - OP3_07
DOI: 10.1055/s-0034-1371982

Leptin-substitution in patients with congenital lipodystrophy increases connectivity in reward-related brain structures: an fMRI study

H Schlögl 1, K Müller 2, A Horstmann 2, 3, B Pleger 2, 4, K Miehle 1, H Möller 2, A Villringer 2, 4, M Fasshauer 1, 3, M Stumvoll 1, 3
  • 1University Hospital Leipzig, Endocrinology, Leipzig, Germany
  • 2Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
  • 3IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany
  • 4University Hospital Leipzig, Day Clinic for Cognitive Neurology, Leipzig, Germany

Patients with congenital lipodystrophy (LD), show reduced leptin serum concentrations, high serum-triglycerides and often a severe diabetes with high insulin demands. Also, patients can develop a disturbed eating behavior. To assess long term effects of leptin substitution on brain connectivity in treatment naïve patients with congenital LD, we performed resting-state functional MRI (fMRI) before and during the initial 52 weeks of treatment.

Methods: The study included 8 leptin-treatment naïve LD patients (6 female, age 36 ± 4 y, BMI 27 ± 2 kg/m2). MRI scannings were performed at 6 timepoints: before leptin supplementation, and after 1, 4, 12, 26, and 52 weeks of treatment. In each session, patients consumed a meal consisting of 20% of their daily energy requirements. Before and after the meal, patients rated satiety feelings using 100 mm visual analog scales (VAS, left 0 mm = no satiety; right 100 mm = extreme satiety).

Results: Glycated haemoglobin (A1c) decreased by 17.1% after 52 weeks of leptin treatment (before leptin treatment 8.3 ± 0.6%, after 52 weeks 6.7 ± 0.5%, p =.13). Satiety ratings after the standard meal increased from 65 ± 10 mm to 93 ± 2 mm, p =.04 after 26 weeks and 71 ± 11 mm, p =.55 after 52 weeks. FMRI analysis showed connectivity increases in nucleus accumbens bilaterally (T = 4.17/4.38), medial frontal gyrus (T = 4.77), and hypothalamus (T = 4.85) over the 52 weeks of treatment (Fig. 1).

Fig. 1

Conclusions: After leptin substitution, patients experienced longer periods of satiety and reduced meal frequencies. Consistently, leptin treated patients showed increased satiety ratings after a meal. During leptin treatment, we also observed a long-term increase of functional connectivity in the nucleus accumbens, an important player in the dopaminergic reward system, suggesting a modulation of this system by leptin. Furthermore, we found increased connectivity of the hypothalamus, the homeostatic control center of the brain, where humoral information from the body converges.