MRI measures of hypothalamic injury are associated with glucagon‐like peptide‐1 receptor agonist treatment response in people with hypothalamic obesity
Open accessAbstract
Aim: To evaluate whether neuroimaging‐delineated regions of hypothalamic injury are associated with a differential treatment response to a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) in patients with hypothalamic obesity (HO). Materials and Methods: We performed a prespecified secondary analysis of a randomized, multicentre, double‐blind, placebo‐controlled trial of people aged 10–25 years with hypothalamic injury and HO randomized to the GLP‐1RA exenatide once‐weekly (ExQW) or placebo for 36 weeks. Subjects underwent MRI prior to enrolment and the degree of hypothalamic damage was assessed using an integrative hypothalamic lesion score (HLS). Mammillary body (MB) damage was specifically determined. The main clinical endpoints were % change in body mass index (BMI) and change in % body fat. Nested ANCOVA models including a treatment × imaging measure interaction were compared using partial F‐tests to assess whether the effect of ExQW treatment differed by severity of hypothalamic damage. Results: Complete data were available in 35/42 randomized participants (placebo, n = 15; ExQW, n = 20). ExQW‐treated patients with worse HLS or bilateral MB damage had greater reductions in % body fat at 36 weeks (interaction coefficient estimates for HLS: −0.9%, 95% CI –1.6% to −0.2%, p = .02; for MB damage: −7.4%, 95% CI –10.1% to −4.7%, p < .001, respectively) but not for BMI % change. Similarly, patients with more damaged and smaller MB cross‐sectional areas had greater reductions in % body fat following ExQW (interaction coefficient estimate 0.3%, 95% CI 0.2%–0.4%, p < .001). Conclusions: In people with HO, greater hypothalamic damage as determined by MRI, in particular MB injury, is associated with greater reductions in adiposity following GLP‐1RA treatment.
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The composite score is predictive of response to antiobesity medication in at least one study.
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Ostrom, Q. T., Gittleman, H. R., Farah, P., Ondracek, A., Chen, Y., Wolinsky, Y., Stroup, N. E., Kruchko, C. A., & Barnholtz‐Sloan, J. S. (2013) · Neuro-Oncology · doi:10.1093/neuonc/not151 · Cited by 12,049 · see citing works
Dolecek, T. A., Propp, J. M., Stroup, N. E., & Kruchko, C. (2012) · Neuro-Oncology · doi:10.1093/neuonc/nos218 · Cited by 1,710 · see citing works
The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss
Secher, A., Jelsing, J., Baquero, A. F., Hecksher-Sørensen, J., Cowley, M. A., Dalbøge, L. S., Hansen, G., Grove, K. L., Pyke, C., Raun, K., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci75276 · Cited by 961 · see citing works
Glucagon-like peptide-1 receptor is involved in learning and neuroprotection
During, M. J., Cao, L., Zuzga, D. S., Francis, J. S., Fitzsimons, H. L., Jiao, X., Bland, R. J., Klugmann, M., Banks, W. A., Drucker, D. J., et al. (2003) · Nature Medicine · doi:10.1038/nm919 · Cited by 851 · see citing works
Puget, S., Garnett, M. R., Wray, A. C., Grill, J., Habrand, J., Boddaert, N., Zérah, M., Bezerra, M., Rénier, D., Pierre‐Kahn, A., et al. (2007) · Journal of Neurosurgery Pediatrics · doi:10.3171/ped.2007.106.1.3 · Cited by 496 · see citing works
GLP-1 Receptor Activation Modulates Appetite- and Reward-Related Brain Areas in Humans
van Bloemendaal, L., IJzerman, R. G., ten Kulve, J. S., Barkhof, F., Konrad, R. J., Drent, M. L., Veltman, D. J., & Diamant, M. (2014) · Diabetes · doi:10.2337/db14-0849 · Cited by 427 · see citing works
Muller, H. L., Gebhardt, U., Teske, C., Faldum, A., Zwiener, I., Warmuth‐Metz, M., Pietsch, T., Pöhl, F., Sørensen, N. S., & Calaminus, G. (2011) · European Journal of Endocrinology · doi:10.1530/eje-11-0158 · Cited by 303 · see citing works
Octreotide Therapy of Pediatric Hypothalamic Obesity: A Double-Blind, Placebo-Controlled Trial
Lustig, R. H., Hinds, P. S., Ringwald-Smith, K., Christensen, R. K., Kaste, S. C., Schreiber, R. E., Rai, S. N., Lensing, S., Wu, S., & Xiong, X. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-030003 · Cited by 299 · see citing works
GLP-1 and weight loss: unraveling the diverse neural circuitry
Kanoski, S. E., Hayes, M. R., & Skibicka, K. P. (2016) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00520.2015 · Cited by 290 · see citing works
Muller, H. L., Emser, A., Faldum, A., Bruhnken, G., Etavard-Gorris, N., Gebhardt, U., Oeverink, R., Kolb, R., & Sørensen, N. S. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031751 · Cited by 288 · see citing works
Farr, O. M., Sofopoulos, M., Tsoukas, M. A., Dincer, F., Thakkar, B., Sahin-Efe, A., Filippaios, A., Bowers, J., Srnka, A., Gavrieli, A., et al. (2016) · Diabetologia · doi:10.1007/s00125-016-3874-y · Cited by 287 · see citing works
Kanoski, S. E., & Grill, H. J. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.09.011 · Cited by 278 · see citing works
Olsson, D. S., Andersson, E., Bryngelsson, I., Nilsson, A. G., & Johannsson, G. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-3525 · Cited by 196 · see citing works
Vile, C. D., Grant, D., Hayward, R. D., Kendall, B. E., Neville, B. G. R., & Stanhope, R. G. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.7.8675604 · Cited by 192 · see citing works
The mammillary bodies and memory
Vann, S. D., & Nelson, A. J. D. (2015) · Progress in brain research · doi:10.1016/bs.pbr.2015.03.006 · Cited by 126 · see citing works
Hamilton, J., Conwell, L., Syme, C., Ahmet, A., Jeffery, A., & Daneman, D. (2011) · International Journal of Pediatric Endocrinology · doi:10.1155/2011/417949 · Cited by 109 · see citing works
GLP‐1 agonists for obesity and type 2 diabetes in children: Systematic review and meta‐analysis
Chadda, K. R., Cheng, T. S., & Ong, K. K. (2020) · Obesity Reviews · doi:10.1111/obr.13177 · Cited by 103 · see citing works
Roth, C. L., Eslamy, H., Werny, D., Elfers, C., Shaffer, M. L., Pihoker, C., Ojemann, J., & Dobyns, W. B. (2015) · Obesity · doi:10.1002/oby.21067 · Cited by 96 · see citing works
Self-citationMEMORY AND THE REGION OF THE MAMMILLARY BODIES
Sziklas, V. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(97)00064-6 · Cited by 88 · see citing works
Roth, C. L., Perez, F. A., Whitlock, K. B., Elfers, C., Yanovski, J. A., Shoemaker, A. H., & Abuzzahab, M. J. (2021) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14224 · Cited by 87 · see citing works
Self-citationVogel, H., Wolf, S., Rabasa, C., Rodriguez-Pacheco, F., Babaei, C. S., Stöber, F., Goldschmidt, J., DiMarchi, R. D., Finan, B., Tschöp, M. H., et al. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.07.039 · Cited by 86 · see citing works
Danielsson, P., Janson, A., Norgren, S., & Marcus, C. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0826 · Cited by 84 · see citing works
Projections from the hippocampal region to the mammillary bodies in macaque monkeys
Aggleton, J. P., Vann, S. D., & Saunders, R. C. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04450.x · Cited by 83 · see citing works
Dexamphetamine Use for Management of Obesity and Hypersomnolence Following Hypothalamic Injury
Ismail, D., O’Connell, M. A., & Zacharin, M. (2006) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2006.19.2.129 · Cited by 80 · see citing works
Perioperative Dexamethasone Treatment in Childhood Craniopharyngioma
Muller, H. L., Heinrich, M., Bueb, K., Etavard-Gorris, N., Gebhardt, U., Kolb, R., & Sörensen, N. (2003) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2003-42722 · Cited by 63 · see citing works
Bojanowska, E. (2005) · PubMed · Cited by 58 · see citing works
López‐Ferreras, L., Eerola, K., Mishra, D., Shevchouk, O. T., Richard, J. E., Nilsson, F. H., Hayes, M. R., & Skibicka, K. P. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.11.005 · Cited by 57 · see citing works
Roth, C. L. (2011) · Frontiers in Endocrinology · doi:10.3389/fendo.2011.00049 · Cited by 54 · see citing works
Self-citationTreatment of Hypothalamic Obesity with Caffeine and Ephedrine
Greenway, F. L., & Bray, G. A. (2008) · Endocrine Practice · doi:10.4158/ep.14.6.697 · Cited by 52 · see citing works
Obesity following combination of rostrolaterial to VMH cut and contralateral mammillary area lesion.
Gold, R. M., Quackenbush, P. M., & Kapatos, G. (1972) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0032523 · Cited by 45 · see citing works
Glucagon-like peptide 1 (GLP-1) and eating
Gutzwiller, J., Degen, L. P., Heuss, L. T., & Beglinger, C. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.04.019 · Cited by 44 · see citing works
Dillingham, C. M., Milczarek, M. M., Perry, J. C., Frost, B. E., Parker, G. D., Assaf, Y., Sengpiel, F., O’Mara, S. M., & Vann, S. D. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.0827-19.2019 · Cited by 37 · see citing works
Time to put the mammillothalamic pathway into context
Dillingham, C. M., Milczarek, M. M., Perry, J. C., & Vann, S. D. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.11.031 · Cited by 37 · see citing works
Shoemaker, A. H., Proietto, J., Abuzzahab, M. J., Markovic, T., Malloy, J. L., & Kim, D. D. H. (2017) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12928 · Cited by 32 · see citing works
Self-citationGut feeling – the secret of satiety?
Bloom, S. R., Wynne, K., & Chaudhri, O. B. (2005) · Clinical Medicine · doi:10.7861/clinmedicine.5-2-147 · Cited by 14 · see citing works
Grewal, S. S., Gupta, V., Vibhute, P. G., Shih, J. J., Tatum, W. O., & Wharen, R. E. (2018) · Epilepsy Research · doi:10.1016/j.eplepsyres.2018.01.021 · Cited by 14 · see citing works
Li, D., Pan, J., Peng, J., Zhang, S., Huang, G., Zhang, X., Bao, Y., & Qi, S. (2017) · Pediatric Research · doi:10.1038/pr.2017.289 · Cited by 11 · see citing works
Morishita, Y., Mugikura, S., Mori, N., Tamura, H., Sato, S., Akashi, T., Jin, K., Nakasato, N., & Takase, K. (2019) · Neuroradiology · doi:10.1007/s00234-019-02158-4 · Cited by 11 · see citing works
Whelan, R., Prince, E. W., Mirsky, D. M., Naftel, R. P., Bhatia, A., Pettorini, B. L., Avula, S., Staulcup, S. J., Alexander, A., Meier, M. R., et al. (2019) · Journal of Neurosurgery Pediatrics · doi:10.3171/2019.8.peds19295 · Cited by 7 · see citing works
Merchenthaler (1999) · doi:10.1002/(sici)1096-9861(19990111)403:2
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Apps, J. R., Muller, H. L., Hankinson, T. C., Yock, T. I., & Martı́nez-Barberá, J. P. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnac035 · Cited by 85 · see citing works
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Diene, G., Angulo, M., Hale, P. M., Jepsen, C. H., Hofman, P. L., Hokken‐Koelega, A. C. S., Ramesh, C. K., Turan, S., & Tauber, M. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac549 · Cited by 77 · see citing works
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Roth, C. L., & McCormack, S. E. (2024) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.15530 · Cited by 42 · see citing works
Self-citationShoemaker, A. H., Silver, H. J., Buchowski, M., Slaughter, J. C., Yanovski, J. A., Elfers, C., Roth, C. L., & Abuzzahab, M. J. (2022) · International Journal of Obesity · doi:10.1038/s41366-021-01043-6 · Cited by 44 · see citing works
Self-citationMcCormack, S. E., Wang, Z., Wade, K., Dedio, A., Cilenti, N. A., Crowley, J., Plessow, F., Bamba, V., Roizen, J. D., Jiang, Y., et al. (2023) · Journal of the Endocrine Society · doi:10.1210/jendso/bvad037 · Cited by 33 · see citing works
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Ng, V. W. W., Gerard, G., Koh, J. J. K., Loke, K. Y., Lee, Y. S., & Ng, N. B. H. (2024) · Clinical Obesity · doi:10.1111/cob.12642 · Cited by 22 · see citing works
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- Authors
- Perez, F. A., Elfers, C., Yanovski, J. A., Shoemaker, A. H., Abuzzahab, M. J., & Roth, C. L.
- Affiliations
- Seattle Children's Hospital (US)
- Seattle Children's Research Institute (US)
- National Institutes of Health (US)
- Vanderbilt University Medical Center (US)
- Children’s Minnesota - St. Paul Hospital (US)
- University of Washington (US)
- Corresponding author
- Roth, Christian L.
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2021-03-29
- Volume
- 23
- Issue
- 7
- Pages
- 1532-1541
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- PMC
- PMC8353597
- OpenAlex
- W3135477176
- Cited by
- 29
- References
- 40
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 10 · 2023: 3 · 2022: 7
- FWCI
- 2.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- hypothalamic obesity, hypothalamic injury, GLP-1 receptor agonists, exenatide once weekly, treatment response, fat loss, childhood obesity
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Exenatide, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Magnetic Resonance Imaging, Obesity
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