β-Hydroxybutyrate elevation as a compensatory response against oxidative stress in cardiomyocytes

Nagao, Manabu; Toh, Ryuji; Irino, Yasuhiro; Mori, Takeki; Nakajima, Hideto; Hara, Tetsuya; Honjo, Tomoyuki; Satomi‐Kobayashi, Seimi; Shinke, Toshiro; Tanaka, Hidekazu; Ishida, Tatsuro; Hirata, Ken‐ichi

doi:10.1016/j.bbrc.2016.05.097

Cited by 80 publications

(79 citation statements)

References 35 publications

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“…As most neurons do not effectively generate high-energy phosphates from fatty acids, but do oxidize ketone bodies when carbohydrates are in short supply, neuroprotective effects of ketone bodies are especially important (Cahill GF Jr, 2006; Edmond et al, 1987; Yang et al, 1987). In oxidative stress models, BDH1 induction and SCOT suppression suggest that ketone body metabolism can be reprogrammed to sustain diverse cell signaling, redox potential, or metabolic requirements (Nagao et al, 2016; Tieu et al, 2003). …”

Section: Ketone Bodies Oxidative Stress and Neuroprotectionmentioning

confidence: 99%

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Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

2017

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Ketone body metabolism is a central node in physiological homeostasis. In this review, we discuss how ketones serve discrete fine-tuning metabolic roles that optimize organ and organism performance in varying nutrient states, and protect from inflammation and injury in multiple organ systems. Traditionally viewed as metabolic substrates enlisted only in carbohydrate restriction, recent observations underscore the importance of ketone bodies as vital metabolic and signaling mediators when carbohydrates are abundant. Complementing a repertoire of known therapeutic options for diseases of the nervous system, prospective roles for ketone bodies in cancer have arisen, as have intriguing protective roles in heart and liver, opening therapeutic options in obesity-related and cardiovascular disease. Controversies in ketone metabolism and signaling are discussed to reconcile classical dogma with contemporary observations.

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Section: Ketone Bodies Oxidative Stress and Neuroprotectionmentioning

confidence: 99%

“…Ketone bodies decrease the grades of cellular damage, injury, death and lower apoptosis in neurons and cardiomyocytes (Haces et al, 2008; Maalouf et al, 2007; Nagao et al, 2016; Tieu et al, 2003). Invoked mechanisms are varied and not always linearly related to concentration.…”

Section: Ketone Bodies Oxidative Stress and Neuroprotectionmentioning

confidence: 99%

Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

2017

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“…2). Accordingly, incubation of cardiomyocytes with BHB increased FOXO3a, MnSOD, and catalase expression and protected against H 2 O 2 toxicity [125]. This supports the hypothesis that ketosis could be used in addition to modern RT techniques such as deep inspiration breath hold [126] to further reduce the risk of late cardiac toxicities from RT involving exposure of the heart.…”

Section: Protection Of Normal Cells During Radiotherapymentioning

confidence: 62%

Fasting, Fats, and Physics: Combining Ketogenic and Radiation Therapy against Cancer

Klement¹

2017

Complement Med Res

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Radiotherapy (RT) is a mainstay in the treatment of solid tumors and works by physicochemical reactions inducing oxidative stress in cells. Because in practice the efficacy of RT is limited by its toxicity to normal tissues, any strategy that selectively increases the radiosensitivity of tumor cells or boosts the radioresistance of normal cells is a valuable adjunct to RT. In this review, I summarize preclinical and clinical data supporting the hypothesis that ketogenic therapy through fasting and/or ketogenic diets can be utilized as such an adjunct in order to improve the outcome after RT, in terms of both higher tumor control and lower normal-tissue complication probability. The first effect relates to the metabolic shift from glycolysis towards mitochondrial metabolism, which selectively increases reactive oxygen species (ROS) production and impairs adenoside triphosphate (ATP) production in tumor cells. The second effect is based on the differential stress resistance phenomenon describing the reprogramming of normal cells, but not tumor cells, from proliferation towards maintenance and stress resistance when glucose and growth factor levels are decreased and ketone body levels are elevated. Underlying both effects are metabolic differences between normal and tumor cells. Ketogenic therapy is a non-toxic and cost-effective complementary treatment option that exploits these differences and deserves further clinical investigation.

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“…Interestingly, Nagao et al recently reported that in pressure-overloaded mice, the gene and protein expression levels of SCOT were decreased in failing hearts, causing βOHB accumulation because of the decline in its utilization. 5 Consequently, increased…”

Section: To the Editormentioning

confidence: 99%

Ketone Bodies Are an Alternative Energy Source and Exert Antioxidant Effects

Hattori¹

2018

Circ J

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β-Hydroxybutyrate elevation as a compensatory response against oxidative stress in cardiomyocytes

Cited by 80 publications

References 35 publications

Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

Fasting, Fats, and Physics: Combining Ketogenic and Radiation Therapy against Cancer

Ketone Bodies Are an Alternative Energy Source and Exert Antioxidant Effects

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