Short-Term Ketogenic Diet Induces a Molecular Response That Is Distinct From Dietary Protein Restriction
dc.contributor.author
Kalafut, Krystle C.
dc.contributor.author
Mitchell, Sarah J.
dc.contributor.author
MacArthur, Michael R.
dc.contributor.author
Mitchell, James R.
dc.date.accessioned
2022-05-04T17:48:41Z
dc.date.available
2022-04-27T03:21:27Z
dc.date.available
2022-05-04T17:48:41Z
dc.date.issued
2022-03-30
dc.identifier.issn
2296-861X
dc.identifier.other
10.3389/fnut.2022.839341
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/543978
dc.identifier.doi
10.3929/ethz-b-000543978
dc.description.abstract
There is increasing interest in utilizing short-term dietary interventions in the contexts of cancer, surgical stress and metabolic disease. These short-term diets may be more feasible than extended interventions and may be designed to complement existing therapies. In particular, the high-fat, low-carbohydrate ketogenic diet (KD), traditionally used to treat epilepsy, has gained popularity as a potential strategy for weight loss and improved metabolic health. In mice, long-term KD improves insulin sensitivity and may extend lifespan and healthspan. Dietary protein restriction (PR) causes increased energy expenditure, weight loss and improved glucose homeostasis. Since KD is inherently a low-protein diet (10% of calories from protein vs. >18% in control diet), here we evaluated the potential for mechanistic overlap between PR and KD via activation of a PR response. Mice were fed control, protein-free (PF), or one of four ketogenic diets with varying protein content for 8 days. PF and KD both decreased body weight, fat mass, and liver weights, and reduced fasting glucose and insulin levels, compared to mice fed the control diet. However, PF-fed animals had significantly improved insulin tolerance compared to KD. Furthermore, contrary to the PF-fed mice, mice fed ketogenic diets containing more than 5% of energy from protein did not increase hepatic Fgf21 or brown adipose Ucp1 expression. Interestingly, mice fed KD lacking protein demonstrated greater elevations in hepatic Fgf21 than mice fed a low-fat PF diet. To further elucidate potential mechanistic differences between PF and KD and the interplay between dietary protein and carbohydrate restriction, we conducted RNA-seq analysis on livers from mice fed each of the six diets and identified distinct gene sets which respond to dietary protein content, dietary fat content, and ketogenesis. We conclude that KD with 10% of energy from protein does not induce a protein restriction response, and that the overlapping metabolic benefits of KD and PF diets may occur via distinct underlying mechanisms.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Frontiers Media
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
ketogenic
en_US
dc.subject
dietary restriction
en_US
dc.subject
protein restriction
en_US
dc.subject
carbohydrate
en_US
dc.subject
protein
en_US
dc.subject
RNA seq
en_US
dc.subject
low protein
en_US
dc.subject
carbohydrate restriction
en_US
dc.title
Short-Term Ketogenic Diet Induces a Molecular Response That Is Distinct From Dietary Protein Restriction
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
Frontiers in Nutrition
ethz.journal.volume
9
en_US
ethz.journal.abbreviated
Front. Nutr.
ethz.pages.start
839341
en_US
ethz.size
12 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Lausanne
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02540 - Institut für Translationale Medizin / Institute of Translational Medicine::09690 - Mitchell, James (ehemalig) / Mitchell, James (former)
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02540 - Institut für Translationale Medizin / Institute of Translational Medicine::09690 - Mitchell, James (ehemalig) / Mitchell, James (former)
ethz.date.deposited
2022-04-27T03:21:39Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2022-05-04T17:48:56Z
ethz.rosetta.lastUpdated
2024-02-02T16:47:57Z
ethz.rosetta.versionExported
true
ethz.COinS
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