ArticleAmerican journal of physiology. Endocrinology and metabolism2010
Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level.
Article in American journal of physiology. Endocrinology and metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 79 citations in OpenAlex.
- Triiodothyronine and leptin repletion in humans similarly reverse weight-loss-induced changes in skeletal muscle.American journal of physiology. Endocrinology and metabolism · 2018Trial
- Thyroid hormone acts independently of the thyroid hormone receptor beta in hepatocytes to improve systemic insulin sensitivity.Hepatology communications · 2026Article
- Overnutrition in mice impairs thyroid hormone biosynthesis and utilization, causing hypothyroidism, despite remarkable thyroidal adaptations.The Journal of clinical investigation · 2026Article
- Differential response of the thyroid axis to high-fat diet-induced inflammation and energy balance deregulation in juvenile and adult rats.Frontiers in endocrinology · 2025Article
- Anorexigenic neuropeptides as anti-obesity and neuroprotective agents: exploring the neuroprotective effects of anorexigenic neuropeptides.Bioscience reports · 2024Review
- Maternal pre-pregnancy obesity modifies the association between first-trimester thyroid hormone sensitivity and gestational Diabetes Mellitus: a retrospective study from Northern China.Diabetology & metabolic syndrome · 2023Article
- Leptin Increases: Physiological Roles in the Control of Sympathetic Nerve Activity, Energy Balance, and the Hypothalamic-Pituitary-Thyroid Axis.International journal of molecular sciences · 2023Review
- The pattern of TSH and fT4 levels across different BMI ranges in a large cohort of euthyroid patients with obesity.Frontiers in endocrinology · 2022Article
- Obesity and Thyroid Axis.International journal of environmental research and public health · 2021Review
- Effect of Thyroid Hormones on Adipose Tissue Flexibility.European thyroid journal · 2021Review
- Sex Dimorphic Responses of the Hypothalamus-Pituitary-Thyroid Axis to Energy Demands and Stress.Frontiers in endocrinology · 2021Review
- Gonadotropin Inhibitory Hormone and Its Receptor: Potential Key to the Integration and Coordination of Metabolic Status and Reproduction.Frontiers in endocrinology · 2021Review
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- Article
- Leptin Receptor Signaling in Sim1-Expressing Neurons Regulates Body Temperature and Adaptive Thermogenesis.Endocrinology · 2019Article
- Sex Dimorphic Responses of the Hypothalamus-Pituitary-Thyroid Axis to Maternal Separation and Palatable Diet.Frontiers in endocrinology · 2019Article
- Tanycytes and the Control of Thyrotropin-Releasing Hormone Flux Into Portal Capillaries.Frontiers in endocrinology · 2019Review
- Article
- Deletion of p22JCI insight · 2017Article
- Advances in TRH signaling.Reviews in endocrine & metabolic disorders · 2016Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The hypothalamic-pituitary-thyroid (HPT) axis is a major contributor in maintaining energy expenditure and body weight, and the adipocyte hormone leptin regulates this axis by increasing TRH levels in the fed state. Leptin stimulates TRH directly in the hypothalamic paraventricular nucleus (PVN; direct pathway) and indirectly by regulating proopiomelnocortin neurons in the hypothalamic arcuate nucleus (ARC; indirect pathway). Whereas the indirect pathway is fully functional in lean animals, it is inactive during diet-induced obesity (DIO) because of the establishment of leptin resistance. Despite this, the HPT axis activity in obese humans and rodents remains within the normal levels or slightly higher. Therefore, in this study, we aimed to determine the mechanism(s) by which the HPT axis is still active despite leptin resistance. With a combination of using the Sprague-Dawley rat physiological model and the Zuker rat that bears a mutation in the leptin receptor, we were able to demonstrate that under DIO conditions the HPT axis is regulated at the central level, but only through the direct pathway of leptin action on TRH neurons. Deiodinase enzymes, which are present in many tissues and responsible for converting thyroid hormones, were not statistically different between lean and DIO animals. These data suggest that the increase in T(4/3) seen in obese animals is due mostly to central leptin action. We also found that T(3) feedback inhibition on the prepro-TRH gene is controlled partially by leptin-induced pSTAT3 signaling via the TRH promoter. This interactive relationship between T(3) and pSTAT3 signaling appears essential to maintain the HPT axis at normal levels in conditions such as obesity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.