ArticleMolecular metabolism2021
Insulin and obesity transform hypothalamic-pituitary-adrenal axis stemness and function in a hyperactive state.
Article in Molecular metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Identification and characterization of the long non-coding RNA NFIA-AS2 as a novel locus for body mass index in American Indians.International journal of obesity (2005) · 2023Pooled it
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- Adverse Events Associated with Clascoterone: A Real-World Pharmacovigilance Study of the Food and Drug Administration Adverse Event Reporting System.Therapeutic innovation & regulatory science · 2026Article
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- Prevalence of obesity and its associated factors among healthcare workers in Malaysia: a scoping review.BMC public health · 2026Article
- Unmasking Hormonal Mechanisms of Hypertension in Obesity.JACC. Basic to translational science · 2026Article
- Association between CT-based adrenal gland volume and 10-year cardiovascular disease risk in patients with diabetes mellitus.Quantitative imaging in medicine and surgery · 2026Article
- Insulin Resistance in Bipolar Disorder: A Real-World Cross-Sectional Study.Journal of personalized medicine · 2026Article
- Sex differences in classic congenital adrenal hyperplasia: a multicenter, real-world analysis.Frontiers in endocrinology · 2026Article
- Metabolic dysfunction and insulin resistance in depression: mechanisms, evidence, and therapeutic implications.Frontiers in psychiatry · 2026Review
- Article
- Unmasking Hormonal Mechanisms of Hypertension in Obesity.medRxiv : the preprint server for health sciences · 2025Article
- Neuropsychiatric Abnormalities in Metabolic Disturbances: Interplay of Adipokines and Neurotransmission.Molecular neurobiology · 2025Review
- Exposure to Extreme Heat Increases Preterm Birth Risk: Hypothetical Pathophysiological Mechanisms.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- The Role of Neuroinflammation in the Comorbidity of Psychiatric Disorders and Internal Diseases.Healthcare (Basel, Switzerland) · 2025Review
- Somatization and Body Composition: Findings from a Cross-Sectional Study on Non-Clinical Young Adults.Healthcare (Basel, Switzerland) · 2025Article
- GLP-1R/NPY2R regulate gene expression, ovarian and adrenal morphology in HFD mice.The Journal of endocrinology · 2025Article
- Post stroke depression: pathogenesis and molecular mechanisms of natural product-based interventions.Frontiers in pharmacology · 2025Review
- Distribution, contribution and regulation of nestinJournal of advanced research · 2024Review
- Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveMetabolic 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.
methodsIn 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.
resultsInsulin 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.
conclusionsIt 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.
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