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Regulation of Ketone Body Metabolism and the Role of PPARα
Open accessAbstract
Ketogenesis and ketolysis are central metabolic processes activated during the response to fasting. Ketogenesis is regulated in multiple stages, and a nuclear receptor peroxisome proliferator activated receptor α (PPARα) is one of the key transcription factors taking part in this regulation. PPARα is an important element in the metabolic network, where it participates in signaling driven by the main nutrient sensors, such as AMP-activated protein kinase (AMPK), PPARγ coactivator 1α (PGC-1α), and mammalian (mechanistic) target of rapamycin (mTOR) and induces hormonal mediators, such as fibroblast growth factor 21 (FGF21). This work describes the regulation of ketogenesis and ketolysis in normal and malignant cells and briefly summarizes the positive effects of ketone bodies in various neuropathologic conditions.
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“This adaptation spares glucose, facilitating sustained fat loss without the loss of lean mass.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [75]
In the citing paper
“Ketone body production (ketogenesis) is crucial for energy provision during caloric restriction, as it reduces glucose demand and muscle breakdown.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [75]
In the citing paper
“Individuals with high PPAR-α expression or activity adapt more readily to fat oxidation, entering ketosis more efficiently.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [75]
In the citing paper
“PPAR-α is a transcription factor that upregulates enzymes involved in ketogenesis, such as HMG-CoA synthase.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [75]
In the citing paper
“Polymorphisms in the PPARA gene can affect the degree of ketogenic adaptation, influencing fat oxidation rates during caloric deficit [75,76].”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [75]
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Physiology and Health Effect of Ketogenic Diet
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Metadata
- Authors
- Grabacka, M., Pierzchalska, M., Dean, M., & Reiss, K.
- Affiliations
- University of Agriculture in Krakow (PL)
- Department of Food Biotechnology, Faculty of Food Technology, University of Agriculture, ul. Balicka 122, 30-149 Kraków, Poland
- Louisiana State University (US)
- Neurological Cancer Research, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, 1700 Tulane Ave, New Orleans, LA 70112, USA
- Corresponding author
- Grabacka, Maja
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2016-12-13
- Volume
- 17
- Issue
- 12
- Pages
- 2093
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC5187893
- OpenAlex
- W2562858475
- Cited by
- 305
- References
- 209
- Citations by year
- 2026: 19 · 2025: 34 · 2024: 26 · 2023: 22 · 2022: 54 · 2021: 42 · 2020: 44 · 2019: 34 · 2018: 25 · 2017: 4
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health, USA (P20-GM103501)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- ketone body metabolism, ketogenesis, ketolysis, PPARα, fasting, AMPK, PGC-1α, mTOR, FGF21, cancer metabolism, neuropathology, nuclear receptors
- MeSH terms
- Animals, Brain, Humans, Ketone Bodies, Neoplasms, Signal Transduction, Neuroprotective Agents, PPAR alpha
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