Brain abnormalities in human obesity: A voxel-based morphometric study

Obesity is accompanied by damage to several tissues. Overweight is a risk factor for Alzheimer's disease and other neurodegenerative disorders. Whether structural abnormalities associated with excess body fat may also occur in the brain is unknown. We sought to determine to what extent excess body fat is associated with regional alterations in brain structure using voxel-based morphometry (VBM), a whole-brain unbiased technique based upon high-definition 3D magnetic resonance imaging (MRI) scans normalized into a common standard space and allowing for an objective assessment of neuroanatomical differences throughout the brain. We studied 24 obese (11 male, 13 female; age: 32 +/- 8 years; body mass index [BMI]: 39.4 +/- 4.7 kg/m2) and 36 lean (25 male, 11 female; mean age: 33 +/- 9 years; BMI: 22.7 +/- 2.2 kg/m2) non-diabetic Caucasians. In comparison with the group of lean subjects, the group of obese individuals had significantly lower gray matter density in the post-central gyrus, frontal operculum, putamen, and middle frontal gyrus (P < 0.01 after adjustment for sex, age, handedness, global tissue density, and multiple comparisons). BMI was negatively associated with GM density of the left post-central gyrus in obese but not lean subjects. This study identified structural brain differences in human obesity in several brain areas previously involved in the regulation of taste, reward, and behavioral control. These alterations may either precede obesity, representing a neural marker of increased propensity to gaining weight, or occur as a consequence of obesity, indicating that also the brain is affected by increased adiposity.

[1]  J T Kuikka,et al.  Regional cerebral blood flow during food exposure in obese and normal-weight women. , 1997, Brain : a journal of neurology.

[2]  H. Münzberg,et al.  Leptin receptor action and mechanisms of leptin resistance , 2005, Cellular and Molecular Life Sciences.

[3]  R. Hampson,et al.  Reward, memory and substance abuse: functional neuronal circuits in the nucleus accumbens , 2004, Neuroscience & Biobehavioral Reviews.

[4]  Karl J. Friston,et al.  Cerebral Asymmetry and the Effects of Sex and Handedness on Brain Structure: A Voxel-Based Morphometric Analysis of 465 Normal Adult Human Brains , 2001, NeuroImage.

[5]  D. Figlewicz,et al.  Adiposity signals and food reward: expanding the CNS roles of insulin and leptin. , 2003, American journal of physiology. Regulatory, integrative and comparative physiology.

[6]  J. O'Callaghan,et al.  Obesity exacerbates chemically induced neurodegeneration , 2002, Neuroscience.

[7]  E. Ravussin,et al.  Neuroanatomical correlates of hunger and satiation in humans using positron emission tomography. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Kewei Chen,et al.  Tasting a liquid meal after a prolonged fast is associated with preferential activation of the left hemisphere , 2002, Neuroreport.

[9]  R. Unger.  Printed in U.S.A. Copyright © 2003 by The Endocrine Society doi: 10.1210/en.2003-0870 Minireview: Weapons of Lean Body Mass Destruction: The Role of Ectopic Lipids in the Metabolic Syndrome , 2022 .

[10]  Nora D. Volkow,et al.  Enhanced resting activity of the oral somatosensory cortex in obese subjects , 2002, Neuroreport.

[11]  Nathan S White,et al.  A voxel-based morphometric study of nondemented adults with Down Syndrome , 2003, NeuroImage.

[12]  Alan C. Evans,et al.  Flavor processing: more than the sum of its parts , 1997, Neuroreport.

[13]  Piotr Bogorodzki,et al.  Cortical and limbic activation during viewing of high- versus low-calorie foods , 2003, NeuroImage.

[14]  Kewei Chen,et al.  Are we addicted to food? , 2003, Obesity research.

[15]  S. Strakowski,et al.  Changes in Gray Matter Volume in Patients with Bipolar Disorder , 2005, Biological Psychiatry.

[16]  Jian-jun Wang,et al.  Cerebellar interpositus nuclear and gastric vagal afferent inputs reach and converge onto glycemia-sensitive neurons of the ventromedial hypothalamic nucleus in rats , 2004, Neuroscience Research.

[17]  Jean Logan,et al.  Brain dopamine and obesity , 2001, The Lancet.

[18]  E. Ravussin,et al.  Neuroimaging and Obesity , 2002, Annals of the New York Academy of Sciences.

[19]  Johanna Kuusisto,et al.  Association between features of the insulin resistance syndrome and alzheimer's disease independently of apolipoprotein e4 phenotype: cross sectional population based study , 1997, BMJ.

[20]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1994, Nature.

[21]  T. Sharma,et al.  The Relationship of Structural Alterations to Cognitive Deficits in Schizophrenia: A Voxel-Based Morphometry Study , 2005, Biological Psychiatry.

[22]  Suzanne Craft,et al.  Insulin and neurodegenerative disease: shared and specific mechanisms , 2004, The Lancet Neurology.

[23]  F Fazio,et al.  Brain abnormalities underlying altered activation in dyslexia: a voxel based morphometry study. , 2005, Brain : a journal of neurology.

[24]  Deborah Gustafson,et al.  An 18-year follow-up of overweight and risk of Alzheimer disease. , 2003, Archives of internal medicine.

[25]  Alan C. Evans,et al.  Changes in brain activity related to eating chocolate: from pleasure to aversion. , 2001, Brain : a journal of neurology.

[26]  Wenzhen Duan,et al.  Neuroprotective and neurorestorative signal transduction mechanisms in brain aging: modification by genes, diet and behavior , 2002, Neurobiology of Aging.

[27]  C. Björkelund,et al.  A 24-year follow-up of body mass index and cerebral atrophy , 2004, Neurology.

[28]  D. Bennett,et al.  Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. , 2004, Archives of neurology.

[29]  B. Jeanrenaud,et al.  Altered neuroanatomical organization in the central nervous system of the genetically obese (ob/ob) mouse , 1979, Brain Research.

[30]  Mark P Mattson,et al.  Dietary restriction enhances neurotrophin expression and neurogenesis in the hippocampus of adult mice , 2002, Journal of neurochemistry.

[31]  Richard J. Beninger,et al.  Microinjections of flupenthixol into the caudate putamen of rats produce intrasession declines in food-rewarded operant responding , 1993, Pharmacology Biochemistry and Behavior.

[32]  E M Reiman,et al.  Effect of satiation on brain activity in obese and lean women. , 2001, Obesity research.

[33]  Geraldo F. Busatto,et al.  Regional Gray Matter Abnormalities in Obsessive-Compulsive Disorder: A Voxel-Based Morphometry Study , 2005, Biological Psychiatry.

[34]  Rüdiger Klein,et al.  Role of Brain Insulin Receptor in Control of Body Weight and Reproduction , 2000 .

[35]  John A Matochik,et al.  Altered brain tissue composition in heavy marijuana users. , 2005, Drug and alcohol dependence.

[36]  Suk-Tak Chan,et al.  Neuroanatomy of adult strabismus: a voxel-based morphometric analysis of magnetic resonance structural scans , 2004, NeuroImage.

[37]  John A Matochik,et al.  Effect of leptin replacement on brain structure in genetically leptin-deficient adults. , 2005, The Journal of clinical endocrinology and metabolism.

[38]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[39]  Alain Dagher,et al.  Feeding-induced dopamine release in dorsal striatum correlates with meal pleasantness ratings in healthy human volunteers , 2003, NeuroImage.

[40]  E M Reiman,et al.  Differential brain responses to satiation in obese and lean men. , 2000, Diabetes.

[41]  John D. Salamone,et al.  Ventrolateral striatal dopamine depletions impair feeding and food handling in rats , 1993, Pharmacology Biochemistry and Behavior.

[42]  Kewei Chen,et al.  Sex differences in the human brain's response to hunger and satiation. , 2002, The American journal of clinical nutrition.

[43]  G. Glover,et al.  Error‐related brain activation during a Go/NoGo response inhibition task , 2001, Human brain mapping.