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Obesity and Hyperphagia With Increased Defective ACTH: A Novel POMC Variant
OBJECTIVE: Patients with pro-opiomelanocortin (POMC) defects generally present with early-onset obesity, hyperphagia, hypopigmentation and adrenocorticotropin (ACTH) deficiency. Rodent models suggest that adequate cleavage of ACTH to α-melanocortin–stimulating hormone (α-MSH) and desacetyl-α-melanoc...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9797039/ https://www.ncbi.nlm.nih.gov/pubmed/35737586 http://dx.doi.org/10.1210/clinem/dgac342 |
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author | van der Valk, Eline S Kleinendorst, Lotte Delhanty, Patric J D van der Voorn, Bibian Visser, Jenny A van Haelst, M M de Graaff, Laura C G Huisman, Martin White, Anne Ito, Shosuke Wakamatsu, Kazumasa de Rijke, Yolanda B van den Akker, Erica L T Iyer, Anand M van Rossum, Elisabeth F C |
author_facet | van der Valk, Eline S Kleinendorst, Lotte Delhanty, Patric J D van der Voorn, Bibian Visser, Jenny A van Haelst, M M de Graaff, Laura C G Huisman, Martin White, Anne Ito, Shosuke Wakamatsu, Kazumasa de Rijke, Yolanda B van den Akker, Erica L T Iyer, Anand M van Rossum, Elisabeth F C |
author_sort | van der Valk, Eline S |
collection | PubMed |
description | OBJECTIVE: Patients with pro-opiomelanocortin (POMC) defects generally present with early-onset obesity, hyperphagia, hypopigmentation and adrenocorticotropin (ACTH) deficiency. Rodent models suggest that adequate cleavage of ACTH to α-melanocortin–stimulating hormone (α-MSH) and desacetyl-α-melanocortin–stimulating hormone (d-α-MSH) by prohormone convertase 2 at the KKRR region is required for regulating food intake and energy balance. METHODS: We present 2 sisters with a novel POMC gene variant, leading to an ACTH defect at the prohormone convertase 2 cleavage site, and performed functional studies of this variant. RESULTS: The patients had obesity, hyperphagia and hypocortisolism, with markerly raised levels of ACTH but unaffected pigmentation. Their ACTH has reduced potency to stimulate the melanocortin (MC) 2 receptor, explaining their hypocortisolism. CONCLUSION: The hyperphagia and obesity support evidence that adequate cleavage of ACTH to α-MSH and d-α-MSH is also required in humans for feeding control. |
format | Online Article Text |
id | pubmed-9797039 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-97970392023-01-03 Obesity and Hyperphagia With Increased Defective ACTH: A Novel POMC Variant van der Valk, Eline S Kleinendorst, Lotte Delhanty, Patric J D van der Voorn, Bibian Visser, Jenny A van Haelst, M M de Graaff, Laura C G Huisman, Martin White, Anne Ito, Shosuke Wakamatsu, Kazumasa de Rijke, Yolanda B van den Akker, Erica L T Iyer, Anand M van Rossum, Elisabeth F C J Clin Endocrinol Metab Online Only Articles OBJECTIVE: Patients with pro-opiomelanocortin (POMC) defects generally present with early-onset obesity, hyperphagia, hypopigmentation and adrenocorticotropin (ACTH) deficiency. Rodent models suggest that adequate cleavage of ACTH to α-melanocortin–stimulating hormone (α-MSH) and desacetyl-α-melanocortin–stimulating hormone (d-α-MSH) by prohormone convertase 2 at the KKRR region is required for regulating food intake and energy balance. METHODS: We present 2 sisters with a novel POMC gene variant, leading to an ACTH defect at the prohormone convertase 2 cleavage site, and performed functional studies of this variant. RESULTS: The patients had obesity, hyperphagia and hypocortisolism, with markerly raised levels of ACTH but unaffected pigmentation. Their ACTH has reduced potency to stimulate the melanocortin (MC) 2 receptor, explaining their hypocortisolism. CONCLUSION: The hyperphagia and obesity support evidence that adequate cleavage of ACTH to α-MSH and d-α-MSH is also required in humans for feeding control. Oxford University Press 2022-06-23 /pmc/articles/PMC9797039/ /pubmed/35737586 http://dx.doi.org/10.1210/clinem/dgac342 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Online Only Articles van der Valk, Eline S Kleinendorst, Lotte Delhanty, Patric J D van der Voorn, Bibian Visser, Jenny A van Haelst, M M de Graaff, Laura C G Huisman, Martin White, Anne Ito, Shosuke Wakamatsu, Kazumasa de Rijke, Yolanda B van den Akker, Erica L T Iyer, Anand M van Rossum, Elisabeth F C Obesity and Hyperphagia With Increased Defective ACTH: A Novel POMC Variant |
title | Obesity and Hyperphagia With Increased Defective ACTH: A Novel POMC Variant |
title_full | Obesity and Hyperphagia With Increased Defective ACTH: A Novel POMC Variant |
title_fullStr | Obesity and Hyperphagia With Increased Defective ACTH: A Novel POMC Variant |
title_full_unstemmed | Obesity and Hyperphagia With Increased Defective ACTH: A Novel POMC Variant |
title_short | Obesity and Hyperphagia With Increased Defective ACTH: A Novel POMC Variant |
title_sort | obesity and hyperphagia with increased defective acth: a novel pomc variant |
topic | Online Only Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9797039/ https://www.ncbi.nlm.nih.gov/pubmed/35737586 http://dx.doi.org/10.1210/clinem/dgac342 |
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