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Open AccessArticle

Ketones Elicit Distinct Alterations in Adipose Mitochondrial Bioenergetics

by 1, 1, 1, 1, 1, 2, 1, 2 and 1,*
1
Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA
2
Department of Exercise Sciences, Brigham Young University, Provo, UT 84602, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(17), 6255;
Received: 6 August 2020 / Revised: 26 August 2020 / Accepted: 27 August 2020 / Published: 29 August 2020
(This article belongs to the Special Issue The Effects of Ketones on Metabolic Function 2.0)
Objective: The rampant growth of obesity worldwide has stimulated explosive research into human metabolism. Energy expenditure has been shown to be altered by diets differing in macronutrient composition, with low-carbohydrate, ketogenic diets eliciting a significant increase over other interventions. The central aim of this study was to explore the effects of the ketone β-hydroxybutyrate (βHB) on mitochondrial bioenergetics in adipose tissue. Methods: We employed three distinct systems—namely, cell, rodent, and human models. Following exposure to elevated βHB, we obtained adipose tissue to quantify mitochondrial function. Results: In every model, βHB robustly increased mitochondrial respiration, including an increase of roughly 91% in cultured adipocytes, 113% in rodent subcutaneous adipose tissue (SAT), and 128% in human SAT. However, this occurred without a commensurate increase in adipose ATP production. Furthermore, in cultured adipocytes and rodent adipose, we quantified and observed an increase in the gene expression involved in mitochondrial biogenesis and uncoupling status following βHB exposure. Conclusions: In conclusion, βHB increases mitochondrial respiration, but not ATP production, in mammalian adipocytes, indicating altered mitochondrial coupling. These findings may partly explain the increased metabolic rate evident in states of elevated ketones, and may facilitate the development of novel anti-obesity interventions. View Full-Text
Keywords: mitochondria; uncoupling; ketones; adipocyte mitochondria; uncoupling; ketones; adipocyte
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Walton, C.M.; Jacobsen, S.M.; Dallon, B.W.; Saito, E.R.; Bennett, S.L.H.; Davidson, L.E.; Thomson, D.M.; Hyldahl, R.D.; Bikman, B.T. Ketones Elicit Distinct Alterations in Adipose Mitochondrial Bioenergetics. Int. J. Mol. Sci. 2020, 21, 6255.

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