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Hypothalamic lesions and adiposity in the rat race: Effects of metabolic state on the regulation of melanocortin circuits

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William Thompson
Wednesday, August 7, 2019
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  • Psicothema 29, 61— Int J Obes Lond 41—

  • This article is also available for rental through DeepDyve. Hetherington, S.

  • Population-based transcriptional profiling Cell type-specific transcriptomics reveal that the expression of hundreds of genes in AgRP and POMC neurons are modified by energy state [ ].

  • He, Q.

B DBSI-derived axial diffusivity. Exercise offers many health benefits related to cardiovascular improvements, hunger control, and blood glucose homeostasis. D DBSI-derived fiber fraction. Marks, B. Mice were placed into a stereotaxic apparatus Stoelting, D and viral injections were performed as previously described [ 1 ], [ 58 ].

You do not currently have access to this article. The joint effects of clinically relevant depressive symptoms and cardiovascular risk factors on incident cardiovascular disease among older adults in the community. An appraisal of trials investigating the effects on macular pigment optical density of lutein and zeaxanthin dietary interventions: a narrative review. Do you have existing references in a PDF or Word document? Article PDF first page preview.

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Obesity-induced neuroinflammation: beyond the hypothalamus. Months 4—6. Pistell, P. Childhood obesity and eating behaviour. Anxa2 and N Endocrinology : — Thus, AgRP neuron subpopulations form parallel and redundant circuits which project to distinct regions and are sufficient to independently evoke food intake.

It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. HetheringtonS. Hypothalamic Lesions and Adiposity in the Rat A. Search Menu. Article PDF first page preview. View Metrics.

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Month 0. Taken together, it is reasonable to hypothesize that obesity-related neuroinflammation impacts the function and hypothakamic of the human brain and could be an underlying mechanism of obesity-associated cognitive impairment. Advanced Search. Randi E. Figure 2. Obesity-related microglial activation in rodents mediates the relationship between synaptic dysfunction and cognitive deficits, which are blocked by inhibition of microglial activation Erion et al.

Sklar CA Craniopharyngioma: endocrine sequalae of treatment. Neuroimaging studies have found both structural and functional abnormalities in obesity, but the mechanisms underlying these differences are not well understood Devoto lesion al. Octreotide was safe and well tolerated. Taken together, it is reasonable to hypothesize that obesity-related neuroinflammation impacts the function and structure of the human brain and could be an underlying mechanism of obesity-associated cognitive impairment. Boston, MA: Springer. Twenty subjects, age 8—18 yr, with intractable weight gain following therapy for tumors were recruited to take part in this study.

  • Most users should sign in with their email address. Reduced right frontal fractional anisotropy correlated with early elevated plasma LDL levels in obese young adults.

  • The effect of energy and fat content labeling on food consumption pattern: a systematic review and meta-analysis.

  • However, one African-American subject with acanthosis nigricans, originally assigned to the placebo group, and who exhibited impaired glucose tolerance at both month 0 and month 6, developed diabetes during the open-label extension, and octreotide was discontinued. A negative response is considered an improvement.

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Obesity is a disease of low-grade chronic systemic inflammation that affects many body organs Gregor and Hotamisligil, Neuroimage 31, — Wang, Q. Since obese individuals show impaired cognitive function relative to non-obese individuals Wright et al. Walker, J.

Sign in via your Institution Sign in. Brain Behav. These neurons impact on neurons expressing the melancortin-4 receptor to regulate energy balance Also, further histopathological studies in postmortem brain are necessary to confirm that the altered DBSI properties we observed in obese humans truly reflect neuroinflammatory processes.

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Hippocampal volumes and other DBSI-derived metrics were not different between obese and non-obese individuals in either cohort. Google Scholar. We also provide an overview on the effects znd physical exercise to induce biophysical changes in the melanocortin circuit which may regulate food intake, glucose metabolism and improve overall metabolic health. The rise in fasting glucose and increased glycemia was not clinically significant or deleterious to overall glucose tolerance. Ablation of arcuate POMC neurons reduces energy expenditure contributing to increased adiposity and metabolic dysfunction [ ].

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Download all slides. Compromised white matter integrity in obesity. The readout of percentage of slices with signal drop-out and signal drop-out severity were 0 and 1, respectively, for every participant in both cohorts. Sue C. Obesity-related microglial activation in rodents mediates the relationship between synaptic dysfunction and cognitive deficits, which are blocked by inhibition of microglial activation Erion et al.

Receive exclusive offers and updates from Oxford Academic. Pediatr Ann 13 : — However, one African-American rhe with acanthosis nigricans, originally assigned to the placebo group, and who exhibited impaired glucose tolerance at both month 0 and month 6, developed diabetes during the open-label extension, and octreotide was discontinued. Yendiki, A. Diabetes 65, —

Interestingly, exercise intensity impacts the magnitude but not direction of calcium dynamics as the neural activity changes were greater with increasing running speeds Fig. Lauridsen, J. The bottom portion of the figure shows cell subtypes based on transcriptional profiling data in Campbell et al. Median, first and third quartiles, 1. For example, the 5-HT 2c R agonist, Lorcaserin [ ], and various GLP-1 analogues [ 61 ] are targeted therapies that have been marketed for blood glucose control and chronic weight management.

1. Introduction

Xu, J. Finally, the adaptive capacity of metabolically relevant circuits has largely focused on the plasticity of these circuits in lean subjects. In two independent cohorts, we showed that a DBSI-derived indicator of neuroinflammation is greater and axonal density is lower in obese compared to non-obese humans. While a direct trigger in the fasting induced plasticity of the melanocortin circuit has yet to be identified, it should be noted that leptin levels fall during a fast [ 342 ]. Peripheral inflammation as indicated by plasma fibrinogen related to alterations in DTI-measured apparent diffusivity in the amygdala Cazettes et al.

Damage to the VMH results in the inability to transduce these peripheral signals, with resultant lesins caloric intake and decreased energy expenditure, leading to incessant energy storage and intractable obesity. Diabetologia 28 : — J Clin Invest : — For example, the 5-HT 2c R agonist, Lorcaserin [ ], and various GLP-1 analogues [ 61 ] are targeted therapies that have been marketed for blood glucose control and chronic weight management. Acta Mol. All authors critically revised the manuscript, contributed to the interpretation of the results, and approved the final version. Weight kg

Increased body mass index is associated with a global and adipowity decrease in white matter microstructural integrity. Cohort 2: Magnetic resonance imaging scanning was performed on the same Siemens Trio 3T scanner with a 12 channel head coil. Issue Section:. View Metrics. DBSI resolves intra-voxel partial volume effects arising from anisotropic and isotropic diffusion signals, and models both simultaneously to obtain the best estimation of anisotropic and isotropic diffusion tensors. Finally, the results of the current study indicate that putative neuroinflammation and associated cognitive impairment occurs even in obese individuals without diabetes. This instrument was administered to both the patient and the parent simultaneously, separately, and in a double-blind fashion.

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Hypothalamic Lesions and Adiposity in the Rat A. Don't already have an Oxford Academic account? You can now search inside your bibliographies. Custom Shortlinks. Sign in with Apple. Read more.

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Don't have an account? Sign In. Class 3 obesity is not associated with same-day admission in obese patients undergoing parathyroidectomy. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.

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  • The joint effects of clinically relevant depressive symptoms and cardiovascular risk factors on incident cardiovascular disease among older adults in the community. Maybe in a tweet, a presentation, Linkedin post, or class?

  • Obesity-induced neuroinflammation: beyond the hypothalamus.

  • Haliloglu B, Bereket A.

  • In several rodent studies, obesity-induced microglia activation and other types of neuroinflammation were frequently observed in hypothalamus, hippocampus, amygdala, and other brain regions Erion et al. Benton, A.

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Tsai, C. Conversely, males are more sensitive to the adiposty effects of centrally administered AgRP [ 85 ], an effect which might also be influenced by estrous cycle in females [ ]. In particular, leptin, serotonin via serotonin 2c and adiposity — 5-HT 2c Radiponectin, and glucagon-like peptide 1 GLP-1 serve to activate, while insulin inhibits POMC neurons via their cognate receptors [ 54852829899,,]. The arrows demonstrate the changes in the circuit depending on the state of the animal - sedentary or exercise. Figure 1. This information is then relayed onto secondary neurons in order to regulate physiological parameters, which promote proper energy and glucose balance.

ORIGINAL RESEARCH article

A Cohort 1: Obese individuals had lower white matter fractional anisotropy FA and axial diffusivity AD than non-obese individuals. Gameiro, F. However, these resources, combined with methods to validate and manipulate these pathways, provide an exciting framework for extensive metabolic circuit analysis. Complications and adverse events were mild and self-limited.

The joint effects of clinically relevant depressive symptoms and cardiovascular risk factors on incident cardiovascular disease among older adults in the community. Need to share your references with someone else? It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Click the new Plagiarism Checker tile on the home page to find out more. HetheringtonA.

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This is reminiscent of cellular properties that may underlie metabolic set points that contribute to homeostatic model systems including kesions weight and blood glucose regulation [ 47, ]. Cohort 1: Magnetic resonance imaging scanning was performed on a Siemens Trio 3T scanner with a 20 channel head coil. Shelly Y. Arch Pediatr Adolesc Med : — Cohort 1: Height and weight measurements were taken by a trained nurse.

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Patients and Methods

Also, to account for the effects of head motion, we also controlled for Adjposity motion measures volume-by-volume translation and rotation. Cohort 2: Magnetic resonance imaging scanning was performed on the same Siemens Trio 3T scanner with a 12 channel head coil. In our experience, anatomical boundaries of the hypothalamus are not clearly visible on MRIs, making it difficult to be certain whether measures are not affected by partial volume effects. This led to the concept that the hypothalamus was an important region of the brain necessary for proper control of energy balance however, the hypothalamic regions involved in regulating food intake and body weight, remained unclear at that time.

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You can now search inside your bibliographies. Twitter Facebook LinkedIn Email. Oxford University Press is a department of lesikns University of Oxford. In addition to the existing yearly pricing, we now have monthly pricing. The effect of energy and fat content labeling on food consumption pattern: a systematic review and meta-analysis. Download all slides. Gluten-free diet can ameliorate the symptoms of non-celiac autoimmune diseases.

Complications and adverse events were mild aviposity self-limited. Erion, J. Reduced right frontal fractional anisotropy correlated with early elevated plasma LDL levels in obese young adults. Cohort 2: Magnetic resonance imaging scanning was performed on the same Siemens Trio 3T scanner with a 12 channel head coil. Over the past 20—30 years, considerable progress has been made in the characterization of brain circuits in murine models leading to the identification of signaling pathways that regulate metabolism.

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This defines leptin as an important trophic factor responsible for the proper formation of hypothalamic circuits during development with ramifications for metabolic disorders. Zhan, J. Select Format Select format.

HetheringtonA. You can now search inside your bibliographies. Sign in via your Institution Sign in. Google Scholar. Some users were having problems with downloading their bibliographies as Word documents, but this should now be fixed.

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Amber Alhadeff Ph. Importantly, the physiological role of leptin receptors in POMC neurons is to improve insulin sensitivity and glucose hypothalamiic [ 121742 ]. This plasticity facilitates adaptations to various metabolic challenges. Eight subjects were receiving human GH therapy. The activity of melanocortin neurons rapidly adapts to interoceptive e. Figure 5. Functionally, the increased excitatory synaptic input has been suggested to be dependent upon NMDARs, which trigger the fasting-induced activation and dendritic spinogenesis [].

Validity of the trail making test as an adipozity of organic brain damage. Fiber photometry 6. Changes in body mass index and prevalence of overweight in survivors of childhood acute lymphoblastic leukemia: role of cranial irradiation. Thus, the rapid changes occurring at the beginning of exercise might reflect compensatory counter-regulatory mechanisms to facilitate exercise performance. Hungry brains: A meta-analytical review of brain activation imaging studies on food perception and appetite in obese individuals. J Clin Invest 65 : — Karen Ringwald-Smith.

These critical questions will need to be answered in order to better understand metabolic disease and facilitate the development of targeted therapies. We postulated that octreotide suppression of early insulin secretion would attenuate the weight gain First, are the calcium dynamics observed after exercise a reversal of the effects observed during exercise? Indeed, the majority of the weight loss in the drug-treated group occurred between months 4 and 6.

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Xiaoping Xiong. Diabetes 65, — Through previous experimental analyses Wang et al.

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Lustig, M. Alterations in the activity of melanocortin neurons can be transient or sustained; lasting from hours to days. Lin, T. Octreotide was safe and well tolerated. Importantly, the hypothalamus was not included in our ROI analyses.

  • Interestingly, NPY released from AgRP terminals into the PBN can also suppress inflammatory pain during hunger [ 7 ], suggesting that different neurotransmitters released from the same AgRP projection subpopulation serve diverse functions that enable food seeking.

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  • Similarly, in humans with obesity, postmortem brain examination shows evidence of gliosis and abnormal microglia activation in the hypothalamus and altered mRNA expression of inflammatory markers in frontal cortex suggestive of neuroinflammation Baufeld et al. Octreotide suppressed insulin, and stabilized weight and BMI.

  • Gluten-free diet can ameliorate the symptoms of non-celiac autoimmune diseases. Try it out in one of your project or watch a video demonstration here.

  • Fiber photometry hiie experiment Ad libitum fed mice underwent the single ramp HIIE protocol as described above. Effect of vagotomy on serum insulin in rats with paraventricular or ventromedial hypothalamic lesions.

Close mobile search navigation Article Navigation. Public Reference Lists. An epidemiological study of externally determined and self-identified mental and physical disability across the spectrum of bipolar disorders. Article Navigation. Oxford Academic. Purchase Subscription prices and ordering Short-term Access To purchase short term access, please sign in to your Oxford Academic account above.

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Neuroimage 88, 79— Figure 1. Also, further histopathological studies in postmortem brain are necessary to confirm that the altered DBSI properties we observed in obese humans truly reflect neuroinflammatory processes. Characteristics of Pediatric vs Adult Pheochromocytomas and Paragangliomas.

In summary, there is increasing evidence that the melanocortin system rrace highly sensitive to metabolic state. Benedict, R. Karen Ringwald-Smith. Appl Physiol Nutr Metab 41 — The main weakness of this study is that data were not available to link DBSI metrics to alterations in inflammation-related behavior or proinflammatory cytokines in plasma or CSF.

Patients were excluded if: 1 they had previously demonstrated voluntary weight loss; 2 they were receiving any medications for weight loss; 3 they exhibited diabetes mellitus although impaired glucose tolerance was allowed ; 4 they had documented cardiac dysfunction precluding normal exercise tolerance, as demonstrated by a shortening fraction of less than 0. In addition, obesity has been associated with cranial insult. In each instance, measurements were negative, arguing against the possibility of fat malabsorption due to octreotide therapy. There are age, sex, and racial differences in adiposity and associated traits including systemic inflammation severity due to physiological, social and psychological factors Thorand et al.

Christensen, Sue C. The datasets generated and used to perform analyses for this study are available upon a request to the corresponding author. Shesh N. Schur, E. Overlap in white matter tracts with significant differences between obese and non-obese groups in both cohorts Cohort 1: Blue-purple ; Cohort 2: Red-yellow.

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Because the change of weight may be partially due to the change in height and due to the unequal ratios of males to females in the two groups, we performed these analyses using a mixed model 24 tat, 25 with the covariates of height, gender, and treatment octreotide and lesionwby which the effect of treatment was estimated and tested by separating from effects of height and gender. Neurotrauma 36, — Recent advances in transcriptomics have now made it possible to directly quantify gene expression of hundreds of individual cells in a population at a time, with the potential to elucidate pathways that counteract weight-loss and discover gene expression profiles of various neurons. Thus, it might be possible that there is an increase in leptin signaling contributing to plasticity of the melanocortin circuit, independent of falling leptin levels. Peripheral inflammation as indicated by plasma fibrinogen related to alterations in DTI-measured apparent diffusivity in the amygdala Cazettes et al.

  • Exclusion criteria included self-reported diabetic medication use or unknown diabetic medication status, current or past history of confounding neurological disorders, depression as assessed by the Beck Depression Inventory II BDI-II Beck et al.

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  • Miller, A. Also, further histopathological studies in postmortem brain are necessary to confirm that the altered DBSI properties we observed in obese humans truly reflect neuroinflammatory processes.

  • Implications for the changes in cellular activity observed during and after exercise The changes in calcium dynamics during exercise are different than the effects observed after exercise, raising several important questions. Future studies may determine whether putative neuroinflammation modulates the relationship between BMI and cognitive performance.

Try it out in one of your project or watch a video demonstration here. Read more. Download hypothalamc slides. The effect of energy and fat content labeling on food consumption pattern: a systematic review and meta-analysis. If you still run into a problem with downloading files, please email support citationsy. Purchase Subscription prices and ordering Short-term Access To purchase short term access, please sign in to your Oxford Academic account above.

Lustig, M. Oxford Academic. Thus, it might be hypothalakic that there is an increase in leptin signaling contributing to plasticity of the melanocortin circuit, independent of falling leptin levels. Past studies employing traditional immunohistochemistry IHC or in situ hybridization techniques were limited by their scope of transcripts or proteins assessed and have a bias towards known markers.

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Hypothalamic Lesions and Adiposity in the Rat A. Oxford University Press is a department of the University of Oxford. Advanced Search. Do you have existing references in a PDF or Word document?

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The green synaptic terminals boutons are meant hypothzlamic represent excitatory synaptic projections or inputs, while the red terminals are inhibitory inputs. Over the past 20—30 years, considerable progress has been made in the characterization of brain adiposity the in murine models leading to the identification of signaling pathways that regulate metabolism. Measuring specific processes related to neuroinflammation e. In the current study, octreotide treatment resulted in a stabilization of weight and BMI, whereas placebo treatment resulted in no change in the rate of weight or BMI gain. However, this GABAergic projection is necessary for food intake, as it suppresses the visceral malaise associated with overconsumption [ 37 ]. Neurotrauma 36, —

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Based on pharmacological blockade or rar deficiency of melanocortin signaling studies [ 635, ], the decreased POMC activity during exercise of ad-lib fed mice predicts a similar shift toward carbohydrate utilization. However, exercise has also been shown to increase leptin sensitivity [ 6375]. Craniopharyngioma: the St.

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  • The role of central dopamine and serotonin in human obesity: lessons learned from molecular neuroimaging studies.

  • The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. Pharmacol Biochem Behav 16 : —

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  • The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Introduction The concept that the brain influences energy balance arose more than century ago. Anxa2; Fig. Endocr Rev 2 : — Diabetologia 20 : —

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Adiposlty Preview. Stamatovic, S. While the plasticity of these metabolic circuits has been largely defined in males, detailed investigation into the cellular and systemic mechanisms involved in this process in females has been greatly understudied. We postulated that octreotide suppression of early insulin secretion would attenuate the weight gain Dual-wavelength fiber photometry Dual-wavelength fiber photometry FP was performed as we and others have previously described [ 97, ]. Most users should sign in with their email address.

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Changes in weight and BMI between bimonthly measurements in patients with hypothalamic obesity treated with either octreotide or placebo. Sex differences in the relation of body composition to markers of inflammation. Degree of fatness after treatment for acute lymphoblastic leukemia in childhood. Effect of vagotomy on serum insulin in rats with paraventricular or ventromedial hypothalamic lesions. Remarkably, this reorganization occurred within 6 h of leptin treatment.

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