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Comparative Study
. 2012 Oct;97(10):3663-71.
doi: 10.1210/jc.2012-1872. Epub 2012 Aug 7.

Functional magnetic resonance imaging analysis of food-related brain activity in patients with lipodystrophy undergoing leptin replacement therapy

Daisuke Aotani  1 , Ken Ebihara, Nobukatsu Sawamoto, Toru Kusakabe, Megumi Aizawa-Abe, Sachiko Kataoka, Takeru Sakai, Hitomi Iogawa, Chihiro Ebihara, Junji Fujikura, Kiminori Hosoda, Hidenao Fukuyama, Kazuwa Nakao
Affiliations
Comparative Study

Functional magnetic resonance imaging analysis of food-related brain activity in patients with lipodystrophy undergoing leptin replacement therapy

Daisuke Aotani et al. J Clin Endocrinol Metab. 2012 Oct.

Abstract

Context: Lipodystrophy is a disease characterized by a paucity of adipose tissue and low circulating concentrations of adipocyte-derived leptin. Leptin-replacement therapy improves eating and metabolic disorders in patients with lipodystrophy.

Objective: The aim of the study was to clarify the pathogenic mechanism of eating disorders in lipodystrophic patients and the action mechanism of leptin on appetite regulation.

Subjects and interventions: We investigated food-related neural activity using functional magnetic resonance imaging in lipodystrophic patients with or without leptin replacement therapy and in healthy controls. We also measured the subjective feelings of appetite.

Results: Although there was little difference in the enhancement of neural activity by food stimuli between patients and controls under fasting, postprandial suppression of neural activity was insufficient in many regions of interest including amygdala, insula, nucleus accumbens, caudate, putamen, and globus pallidus in patients when compared with controls. Leptin treatment effectively suppressed postprandial neural activity in many of these regions of interest, whereas it showed little effect under fasting in patients. Consistent with these results, postprandial formation of satiety feeling was insufficient in patients when compared with controls, which was effectively reinforced by leptin treatment.

Conclusions: This study demonstrated the insufficiency of postprandial suppression of food-related neural activity and formation of satiety feeling in lipodystrophic patients, which was effectively restored by leptin. The findings in this study emphasize the important pathological role of leptin in eating disorders in lipodystrophy and provide a clue to understanding the action mechanism of leptin in human, which may lead to development of novel strategies for prevention and treatment of obesity.

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Figures

Fig. 1.
Fig. 1.
Neural response to food-specific stimuli in healthy controls and leptin-off patients. Food-specific activations in ROI in the brains of controls (A and B) and patients (C and D) under fasting (A and C) and postprandial (B and D) conditions. Activation is overlaid onto the group average T1-weighted anatomical axial images (right is right side of the brain). The brighter yellow color represents the higher Z-score. ROI areas are the hypothalamus, orbitofrontal cortex (OFC), amygdala, hippocampus, insula, nucleus accumbens (Nacs), caudate, putamen, and globus pallidus (G. pallidus).
Fig. 2.
Fig. 2.
Subjective feelings of appetite under fasting and postprandial conditions in healthy controls and leptin-off patients. A, Hunger scores on the 100-mm VAS before fMRI scan. B, Mean value of rating scores for food pictures during the fMRI scan. Data are means ± sem (n = 10 in each group). *, P < 0.01 (repeated measure ANOVA).
Fig. 3.
Fig. 3.
Neural response to food-specific stimuli in leptin-on patients. Food-specific activations in ROI in the brain under fasting (A) and postprandial (B) conditions. Activation is overlaid onto the group average T1-weighted anatomical axial images (right is right side of the brain). The brighter yellow color represents the higher Z-score. ROI areas are the same as described in Fig. 1.
Fig. 4.
Fig. 4.
Subjective feelings of appetite under fasting and postprandial conditions in patients with leptin-on and leptin-off. A, Hunger scores on the 100-mm VAS before the fMRI scan. B, Mean value of rating scores for food pictures during the fMRI scan. Data are means ± sem (n = 10 in each group). *, P < 0.01 (repeated measure ANOVA).
See this image and copyright information in PMC

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