Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

The Effects of Ketones on Metabolic Function 2.0

Special Issue Editors
Special Issue Information
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 63076

Share This Special Issue

Special Issue Editors

Dr. Benjamin T. Bikman

E-Mail Website
Guest Editor

Associate Professor, Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA
Interests: effects of insulin; ketones on cellular metabolism; mitochondrial function
Special Issues, Collections and Topics in MDPI journals

Dr. Kelsey Fisher-Wellman

E-Mail
Guest Editor

East Carolina Diabetes and Obesity Institute, the Brody School of Medicine, Department of Physiology, East Carolina University, Greenville, United States
Interests: mitochondrial physiology; ketone biochemistry

Special Issue Information

Dear Colleagues,

Once considered “metabolic garbage”, ketones have become the focus of significant efforts within the realm of cardiometabolic research. Recent discoveries have revealed that ketones, such as acetoacetate and its precursor β-hydroxybutyrate (β-HB), are not only viable fuel sources for all cells with mitochondria, including the brain, but are also legitimate signaling molecules, eliciting advantageous changes in inflammation, cognition, oxidative stress, and more. Beyond pathology, ketones may also be a relevant metabolic fuel in the context of physical activity, insofar as ketone-adapted athletes appear to outperform conventional glucose-adapted athletes. Whether through diets sufficiently low in carbohydrate consumption to induce hepatic ketogenesis or the consumption of exogenous ketones, limited evidence suggests a generally favorable metabolic milieu.

We invite authors to contribute original research articles, as well as review articles that will illustrate and stimulate the blossoming effort to understand the role of ketones in diverse metabolic models and conditions. The accepted papers will highlight to readers the metabolic relevance of ketones and, thus, potentially provide a new paradigm on the role of ketones in altering cellular function.

Dr. Benjamin T. Bikman

Dr.Kelsey Fisher-Wellman
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (5 papers)

Download All Papers

Editorial

Jump to: Research, Review

3 pages, 168 KiB

Open AccessEditorial

The Metabolic Effects of Ketones

by Benjamin T. Bikman and Kelsey H. Fisher-Wellman

Int. J. Mol. Sci. 2021, 22(15), 8292; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22158292 - 02 Aug 2021

Viewed by 2347

Abstract

The phrase “once trash, now a treasure” is an apt description of the evolving view of ketones in biomedical research [...] Full article

(This article belongs to the Special Issue The Effects of Ketones on Metabolic Function 2.0)

Research

Jump to: Editorial, Review

15 pages, 907 KiB

Open AccessArticle

The Role of GPR109a Signaling in Niacin Induced Effects on Fed and Fasted Hepatic Metabolism

by Caroline E. Geisler, Kendra E. Miller, Susma Ghimire and Benjamin J. Renquist

Int. J. Mol. Sci. 2021, 22(8), 4001; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084001 - 13 Apr 2021

Cited by 13 | Viewed by 3341

Abstract

Signaling through GPR109a, the putative receptor for the endogenous ligand β-OH butyrate, inhibits adipose tissue lipolysis. Niacin, an anti-atherosclerotic drug that can induce insulin resistance, activates GPR109a at nM concentrations. GPR109a is not essential for niacin to improve serum lipid profiles. To better understand the involvement of GPR109a signaling in regulating glucose and lipid metabolism, we treated GPR109a wild-type (+/+) and knockout (−/−) mice with repeated overnight injections of saline or niacin in physiological states characterized by low (ad libitum fed) or high (16 h fasted) concentrations of the endogenous ligand, β-OH butyrate. In the fed state, niacin increased expression of apolipoprotein-A1 mRNA and decreased sterol regulatory element-binding protein 1 mRNA independent of genotype, suggesting a possible GPR109a independent mechanism by which niacin increases high-density lipoprotein (HDL) production and limits transcriptional upregulation of lipogenic genes. Niacin decreased fasting serum non-esterified fatty acid concentrations in both GPR109a +/+ and −/− mice. Independent of GPR109a expression, niacin blunted fast-induced hepatic triglyceride accumulation and peroxisome proliferator-activated receptor α mRNA expression. Although unaffected by niacin treatment, fasting serum HDL concentrations were lower in GPR109a knockout mice. Surprisingly, GPR109a knockout did not affect glucose or lipid homeostasis or hepatic gene expression in either fed or fasted mice. In turn, GPR109a does not appear to be essential for the metabolic response to the fasting ketogenic state or the acute effects of niacin. Full article

(This article belongs to the Special Issue The Effects of Ketones on Metabolic Function 2.0)

► Show Figures

Figure 1

17 pages, 2321 KiB

Open AccessArticle

Ingested Ketone Ester Leads to a Rapid Rise of Acetyl-CoA and Competes with Glucose Metabolism in the Brain of Non-Fasted Mice

by Laurent Suissa, Pavel Kotchetkov, Jean-Marie Guigonis, Emilie Doche, Ophélie Osman, Thierry Pourcher and Sabine Lindenthal

Int. J. Mol. Sci. 2021, 22(2), 524; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020524 - 07 Jan 2021

Cited by 15 | Viewed by 4426

Abstract

The role of ketone bodies in the cerebral energy homeostasis of neurological diseases has begun to attract recent attention particularly in acute neurological diseases. In ketogenic therapies, ketosis is achieved by either a ketogenic diet or by the administration of exogenous ketone bodies. The oral ingestion of the ketone ester (KE), (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, is a new method to generate rapid and significant ketosis (i.e., above 6 mmol/L) in humans. KE is hydrolyzed into β-hydroxybutyrate (βHB) and its precursor 1,3-butanediol. Here, we investigate the effect of oral KE administration (3 mg KE/g of body weight) on brain metabolism of non-fasted mice using liquid chromatography in tandem with mass spectrometry. Ketosis (Cmax = 6.83 ± 0.19 mmol/L) was obtained at Tmax = 30 min after oral KE-gavage. We found that βHB uptake into the brain strongly correlated with the plasma βHB concentration and was preferentially distributed in the neocortex. We showed for the first time that oral KE led to an increase of acetyl-CoA and citric cycle intermediates in the brain of non-fasted mice. Furthermore, we found that the increased level of acetyl-CoA inhibited glycolysis by a feedback mechanism and thus competed with glucose under physiological conditions. The brain pharmacodynamics of this oral KE strongly suggest that this agent should be considered for acute neurological diseases. Full article

(This article belongs to the Special Issue The Effects of Ketones on Metabolic Function 2.0)

► Show Figures

Figure 1

14 pages, 1891 KiB

Open AccessArticle

Ketones Elicit Distinct Alterations in Adipose Mitochondrial Bioenergetics

by Chase M. Walton, Samuel M. Jacobsen, Blake W. Dallon, Erin R. Saito, Shantelle L. H. Bennett, Lance E. Davidson, David M. Thomson, Robert D. Hyldahl and Benjamin T. Bikman

Int. J. Mol. Sci. 2020, 21(17), 6255; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176255 - 29 Aug 2020

Cited by 15 | Viewed by 20515

Abstract

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. Full article

(This article belongs to the Special Issue The Effects of Ketones on Metabolic Function 2.0)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

17 pages, 1198 KiB

Open AccessReview

Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases

by Nicole Jacqueline Jensen, Helena Zander Wodschow, Malin Nilsson and Jørgen Rungby

Int. J. Mol. Sci. 2020, 21(22), 8767; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228767 - 20 Nov 2020

Cited by 183 | Viewed by 31187

Abstract

Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain’s utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain’s metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain’s glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer’s disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson’s disease and cognitive benefits in patients with—or at risk of—Alzheimer’s disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data. Full article

(This article belongs to the Special Issue The Effects of Ketones on Metabolic Function 2.0)

► Show Figures