ArticleEndocrinology2018
Dietary Manipulations That Induce Ketosis Activate the HPA Axis in Male Rats and Mice: A Potential Role for Fibroblast Growth Factor-21.
Article in Endocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Effects of Rapid Weight Loss on the Immune System in Combat Sports Athletes: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Glucose Dysregulation as a Driver of Autoimmune Mimicry, Inflammation, and Psychiatric Symptoms: A Narrative Review.Biology · 2026Review
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- The allostatic triage model of psychopathology (ATP Model): How reallocation of brain energetic resources under stress elicits psychiatric symptoms.Neuroscience and biobehavioral reviews · 2025Review
- "Feeding the Rhythm"-Effects of Food and Nutrients on Daily Cortisol Secretion: From Molecular Mechanisms to Clinical Impact.International journal of molecular sciences · 2025Review
- Chronic stress inhibits weight gain and decreases beta-hydroxybutyrate levels and glucose tolerance in female BALB/c fed a high-fat ketogenic diet.BMC nutrition · 2025Article
- The Impact of Human Liver Transplantation on the Concentration of Fibroblast Growth Factors: FGF19 and FGF21.International journal of molecular sciences · 2025Article
- The Effects of Eating a Traditional High Fat/High Carbohydrate or a Ketogenic Diet on Sensitivity of Female Rats to Morphine.The Journal of pharmacology and experimental therapeutics · 2024Article
- FGF21 mediating the Sex-dependent Response to Dietary Macronutrients.The Journal of clinical endocrinology and metabolism · 2024Review
- Review
- Dietary Influence on Drug Efficacy: A Comprehensive Review of Ketogenic Diet-Pharmacotherapy Interactions.Nutrients · 2024Review
- FGF21 Induces Skeletal Muscle Atrophy and Increases Amino Acids in Female Mice: A Potential Role for Glucocorticoids.Endocrinology · 2024Article
- Ketogenic diet and behavior: insights from experimental studies.Frontiers in nutrition · 2024Review
- Ketogenic diet for mood disorders from animal models to clinical application.Journal of neural transmission (Vienna, Austria : 1996) · 2023Review
- Effects of very low-calorie ketogenic diet on hypothalamic-pituitary-adrenal axis and renin-angiotensin-aldosterone system.Journal of endocrinological investigation · 2023Review
- Short- and long-term cognitive and metabolic effects of medium-chain triglyceride supplementation in rats.Heliyon · 2023Article
- Circulating FGF21 vs. Stress Markers in Girls during Childhood and Adolescence, and in Their Caregivers: Intriguing Inter-Relations between Overweight/Obesity, Emotions, Behavior, and the Cared-Caregiver Relationship.Children (Basel, Switzerland) · 2022Article
- Effects of an interdisciplinary weight loss program on fibroblast growth factor 21 and inflammatory biomarkers in women with overweight and obesity.Archives of endocrinology and metabolism · 2021Article
- Heart failure-emerging roles for the mitochondrial pyruvate carrier.Cell death and differentiation · 2021Review
- The Nuanced Metabolic Functions of Endogenous FGF21 Depend on the Nature of the Stimulus, Tissue Source, and Experimental Model.Frontiers in endocrinology · 2021Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
In response to an acute threat to homeostasis or well-being, the hypothalamic-pituitary-adrenocortical (HPA) axis is engaged. A major outcome of this HPA axis activation is the mobilization of stored energy, to fuel an appropriate behavioral and/or physiological response to the perceived threat. Importantly, the extent of HPA axis activity is thought to be modulated by an individual's nutritional environment. In this study, we report that nutritional manipulations signaling a relative depletion of dietary carbohydrates, thereby inducing nutritional ketosis, acutely and chronically activate the HPA axis. Male rats and mice maintained on a low-carbohydrate high-fat ketogenic diet (KD) exhibited canonical markers of chronic stress, including increased basal and stress-evoked plasma corticosterone, increased adrenal sensitivity to adrenocorticotropin hormone, increased stress-evoked c-Fos immunolabeling in the paraventricular nucleus of the hypothalamus, and thymic atrophy, an indicator of chronic glucocorticoid exposure. Moreover, acutely feeding medium-chain triglycerides (MCTs) to rapidly induce ketosis among chow-fed male rats and mice also acutely increased HPA axis activity. Lastly, and consistent with a growing literature that characterizes the hepatokine fibroblast growth factor-21 (FGF21) as both a marker of the ketotic state and as a key metabolic stress hormone, the HPA response to both KD and MCTs was significantly blunted among mice lacking FGF21. We conclude that dietary manipulations that induce ketosis lead to increased HPA axis tone, and that the hepatokine FGF21 may play an important role to facilitate this effect.
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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.