PPARs and the orchestration of metabolic fuel selection
Abstract
This contribution describes recent advances in our knowledge of the regulatory interactions between the two major oxidative fuels glucose and lipid. It also addresses how the metabolic abnormalities associated with insulin resistance and ischemic diseases impair the ability of skeletal muscle to switch between the use of alternative metabolic fuels and the ability of adipose tissue to function appropriately in relation to the body's requirements for triglyceride mobilisation or storage, as appropriate to nutritional status. We discuss how targeting PPARs might ameliorate metabolic inflexibility in muscle through altered expression of pyruvate dehydrogenase kinase (PDK) isoforms and impact the functions of the adipocyte in lipid buffering and energy homeostasis. Focus has been placed on the participation of the regulatory pyruvate dehydrogenase kinases, PPAR targets, both in the beneficial and the potentially adverse actions of the PPARs in metabolic control.
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Dysregulation of pyruvate metabolism contributes to the pathogenesis of numerous diseases, including diabetes and obesity, mitochondrial disorders, cardiac failure, neurodegenerative disorders, and cancer.
“Dysregulation of these processes contributes to the pathogenesis of numerous diseases, including diabetes and obesity (DeFronzo and Tripathy, 2009; Sugden et al., 2009), mitochondrial disorders (Kerr, 2013), cardiac failure (Fillmore and Lopaschuk, 2013), neurodegenerative disorders (Cunnane et al., 2011; Yao et al., 2011), and cancer (Currie et al., 2013; Tennant et al., 2010).”
From Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier (2014) · cites this paper as Sugden et al., 2009
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The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility
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- Authors
- Sugden, M. C., Zariwala, M. G., & Holness, M. J.
- Affiliations
- Queen Mary University of London (GB)
- ORCID
- Zariwala, M. Gulrez
- Venue
- Pharmacological Research
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 60
- Issue
- 3
- Pages
- 141-150
- ISSN
- 1043-6618 (ISSN-L)
- OpenAlex
- W2090782359
- Cited by
- 64
- References
- 130
- Citations by year
- 2025: 2 · 2024: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 10 · 2014: 6 · 2013: 7 · 2012: 6
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacological Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Diabetes UK
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- peroxisome proliferator-activated receptors, glycolipid metabolism, insulin resistance, adipose tissue, energy homeostasis, pyruvate dehydrogenase kinase, ischemic diseases
- MeSH terms
- Adipose Tissue, Animals, Energy Metabolism, Fatty Acids, Glucose, Humans, Insulin Resistance, Ischemia, Mitochondria, Muscle, Obesity, Stress, Physiological, Peroxisome Proliferator-Activated Receptors, Lipid Metabolism
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