ArticleProceedings of the National Academy of Sciences of the United States of America2016
Central role for melanocortin-4 receptors in offspring hypertension arising from maternal obesity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- Maternal obesity and offspring cardiovascular remodelling - the effect of preconception and antenatal lifestyle interventions: a systematic review.International journal of obesity (2005) · 2024Pooled it
- Maternal overnutrition elevates offspring's blood pressure-A systematic review and meta-analysis.Paediatric and perinatal epidemiology · 2022Pooled it
- Lifestyle intervention in obese pregnancy and cardiac remodelling in 3-year olds: children of the UPBEAT RCT.International journal of obesity (2005) · 2022Trial
- Parental Obesity and Offspring Risk for Cardiorenal Diseases.Current hypertension reports · 2026Review
- Cardiometabolic regulation by adipocyte-derived leptin and the brain melanocortin system.Clinical science (London, England : 1979) · 2026Review
- Early-life programming of hypothalamic circuits by maternal obesity: implications for neuroendocrine disorders.Reviews in endocrine & metabolic disorders · 2026Review
- Maternal high-fat diet exposure is associated with altered hypothalamic microglial development and reduced early postnatal TGFβ1 signaling in male offspring.Frontiers in endocrinology · 2026Article
- Neonatal hyperoxia exposure does not exacerbate hypertension programmed by maternal obesity.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Article
- Neural and hormonal mechanisms of appetite regulation during eating.Frontiers in nutrition · 2025Review
- Sex differences in the sensitization of prenatally programmed hypertension.Frontiers in physiology · 2025Review
- Guidelines for in vivo models of developmental programming of cardiovascular disease risk.American journal of physiology. Heart and circulatory physiology · 2024Review
- Thyroid Hormone Clearance in the Paraventricular Nucleus of Male Mice Regulates Lean Mass and Physical Activity.Neuroendocrinology · 2024Article
- Sex differences in weight gain, blood pressure control, and responses to melanocortin-4 receptor antagonism in offspring from lean and obese parents.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- Nutrition and Developmental Origins of Kidney Disease.Nutrients · 2023Review
- Mechanisms mediating the impact of maternal obesity on offspring hypothalamic development and later function.Frontiers in endocrinology · 2022Review
- Hypothalamic MC4R regulates glucose homeostasis through adrenaline-mediated control of glucose reabsorption via renal GLUT2 in mice.Diabetologia · 2021Article
- Role of the Melanocortin System in the Central Regulation of Cardiovascular Functions.Frontiers in physiology · 2021Review
- Anomalous AMPK-regulated angiotensin ATJournal of biomedical science · 2020Article
- High-fat diet from parental generation exaggerates body and adipose tissue weights in pregnant offspring.PloS one · 2020Article
- Prenatal cold exposure causes hypertension in offspring by hyperactivity of the sympathetic nervous system.Clinical science (London, England : 1979) · 2019Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Melanocortin-4 receptor (Mc4r)-expressing neurons in the autonomic nervous system, particularly in the paraventricular nucleus of the hypothalamus (PVH), play an essential role in blood pressure (BP) control. Mc4r-deficient (Mc4rKO) mice are severely obese but lack obesity-related hypertension; they also show a reduced pressor response to salt loading. We have previously reported that lean juvenile offspring born to diet-induced obese rats (OffOb) exhibit sympathetic-mediated hypertension, and we proposed a role for postnatally raised leptin in its etiology. Here, we test the hypothesis that neonatal hyperleptinemia due to maternal obesity induces persistent changes in the central melanocortin system, thereby contributing to offspring hypertension. Working on the OffOb paradigm in both sexes and using transgenic technology to restore Mc4r in the PVH of Mc4rKO (Mc4rPVH) mice, we have now shown that these mice develop higher BP than Mc4rKO or WT mice. We have also found that experimental hyperleptinemia induced in the neonatal period in Mc4rPVH and WT mice, but not in the Mc4rKO mice, leads to heightened BP and severe renal dysfunction. Thus, Mc4r in the PVH appears to be required for early-life programming of hypertension arising from either maternal obesity or neonatal hyperleptinemia. Early-life exposure of the PVH to maternal obesity through postnatal elevation of leptin may have long-term consequences for cardiovascular health.
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