Insulin and obesity transform hypothalamic-pituitary-adrenal axis stemness and function in a hyperactive state.
Animals
Cell Differentiation
/ drug effects
Cell Proliferation
/ drug effects
Female
Hypothalamo-Hypophyseal System
/ metabolism
Insulin
/ metabolism
Leptin
/ metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Obese
Mice, Transgenic
Obesity
/ metabolism
Pituitary-Adrenal System
/ metabolism
Stem Cells
/ drug effects
Stress, Physiological
/ physiology
Adrenal
HPA axis
Metabolic stress
Obesity
Pituitary
Progenitors
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
28
08
2020
revised:
22
10
2020
accepted:
03
11
2020
pubmed:
7
11
2020
medline:
31
8
2021
entrez:
6
11
2020
Statut:
ppublish
Résumé
Metabolic diseases are an increasing problem in society with the brain-metabolic axis as a master regulator of the human body for sustaining homeostasis under metabolic stress. However, metabolic inflammation and disease will trigger sustained activation of the hypothalamic-pituitary-adrenal axis. In this study, we investigated the role of metabolic stress on progenitor cells in the hypothalamic-pituitary-adrenal axis. In vitro, we applied insulin and leptin to murine progenitor cells isolated from the pituitary and adrenal cortex and examined the role of these hormones on proliferation and differentiation. In vivo, we investigated two different mouse models of metabolic disease, obesity in leptin-deficient ob/ob mice and obesity achieved via feeding with a high-fat diet. Insulin was shown to lead to enhanced proliferation and differentiation of both pituitary and adrenocortical progenitors. No alterations in the progenitors were noted in our chronic metabolic stress models. However, hyperactivation of the hypothalamic-pituitary-adrenal axis was observed and the expression of the appetite-regulating genes Npy and Agrp changed in both the hypothalamus and adrenal. It is well-known that chronic stress and stress hormones such as glucocorticoids can induce metabolic changes including obesity and diabetes. In this article, we show for the first time that this might be based on an early sensitization of stem cells of the hypothalamic-pituitary-adrenal axis. Thus, pituitary and adrenal progenitor cells exposed to high levels of insulin are metabolically primed to a hyper-functional state leading to enhanced hormone production. Likewise, obese animals exhibit a hyperactive hypothalamic-pituitary-adrenal axis leading to adrenal hyperplasia. This might explain how stress in early life can increase the risk for developing metabolic syndrome in adulthood.
Identifiants
pubmed: 33157254
pii: S2212-8778(20)30186-1
doi: 10.1016/j.molmet.2020.101112
pmc: PMC7691554
pii:
doi:
Substances chimiques
Insulin
0
Leptin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101112Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.
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