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.
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.
Authors: J L Lancaster; M G Woldorff; L M Parsons; M Liotti; C S Freitas; L Rainey; P V Kochunov; D Nickerson; S A Mikiten; P T Fox Journal: Hum Brain Mapp Date: 2000-07 Impact factor: 5.038
Authors: N Tzourio-Mazoyer; B Landeau; D Papathanassiou; F Crivello; O Etard; N Delcroix; B Mazoyer; M Joliot Journal: Neuroimage Date: 2002-01 Impact factor: 6.556
Authors: S Shackleton; D J Lloyd; S N Jackson; R Evans; M F Niermeijer; B M Singh; H Schmidt; G Brabant; S Kumar; P N Durrington; S Gregory; S O'Rahilly; R C Trembath Journal: Nat Genet Date: 2000-02 Impact factor: 38.330
Authors: J Magré; M Delépine; E Khallouf; T Gedde-Dahl; L Van Maldergem; E Sobel; J Papp; M Meier; A Mégarbané; A Bachy; A Verloes; F H d'Abronzo; E Seemanova; R Assan; N Baudic; C Bourut; P Czernichow; F Huet; F Grigorescu; M de Kerdanet; D Lacombe; P Labrune; M Lanza; H Loret; F Matsuda; J Navarro; A Nivelon-Chevalier; M Polak; J J Robert; P Tric; N Tubiana-Rufi; C Vigouroux; J Weissenbach; S Savasta; J A Maassen; O Trygstad; P Bogalho; P Freitas; J L Medina; F Bonnicci; B I Joffe; G Loyson; V R Panz; F J Raal; S O'Rahilly; T Stephenson; C R Kahn; M Lathrop; J Capeau Journal: Nat Genet Date: 2001-08 Impact factor: 38.330
Authors: Elif Arioglu Oral; Vinaya Simha; Elaine Ruiz; Alexa Andewelt; Ahalya Premkumar; Peter Snell; Anthony J Wagner; Alex M DePaoli; Marc L Reitman; Simeon I Taylor; Phillip Gorden; Abhimanyu Garg Journal: N Engl J Med Date: 2002-02-21 Impact factor: 91.245
Authors: Kitt Falk Petersen; Elif Arioglu Oral; Sylvie Dufour; Douglas Befroy; Charlotte Ariyan; Chunli Yu; Gary W Cline; Alex M DePaoli; Simeon I Taylor; Phillip Gorden; Gerald I Shulman Journal: J Clin Invest Date: 2002-05 Impact factor: 14.808
Authors: L Van Maldergem; J Magré; T E Khallouf; T Gedde-Dahl; M Delépine; O Trygstad; E Seemanova; T Stephenson; C S Albott; F Bonnici; V R Panz; J L Medina; P Bogalho; F Huet; S Savasta; A Verloes; J J Robert; H Loret; M De Kerdanet; N Tubiana-Rufi; A Mégarbané; J Maassen; M Polak; D Lacombe; C R Kahn; E L Silveira; F H D'Abronzo; F Grigorescu; M Lathrop; J Capeau; S O'Rahilly Journal: J Med Genet Date: 2002-10 Impact factor: 6.318
Authors: X Prieur; L Dollet; M Takahashi; M Nemani; B Pillot; C Le May; C Mounier; H Takigawa-Imamura; D Zelenika; F Matsuda; B Fève; J Capeau; M Lathrop; P Costet; B Cariou; J Magré Journal: Diabetologia Date: 2013-05-17 Impact factor: 10.122
Authors: Joe J Simon; Mandy Skunde; Maria Hamze Sinno; Timo Brockmeyer; Sabine C Herpertz; Martin Bendszus; Wolfgang Herzog; Hans-Christoph Friederich Journal: Front Behav Neurosci Date: 2014-10-17 Impact factor: 3.558