A low fat diet ameliorates pathology but retains beneficial effects associated with CPT1b knockout in skeletal muscle
Open accessAbstract
Inhibiting fatty acid oxidation is one approach to lowering glucose levels in diabetes. Skeletal muscle specific Carnitine Palmitoyltransferase 1b knockout mice (Cpt1bm-/-) comprise a model of impaired fat oxidation; and have decreased fat mass and enhanced glucose disposal and muscle oxidative capacity compared to controls. However, unfavorable effects occur relative to controls when Cpt1bm-/- mice are fed a 25% fat diet, including decreased activity and fat free mass and increased intramuscular lipid and serum myoglobin. In this study we explore if a low fat, high carbohydrate diet can ablate the unfavorable effects while maintaining the favorable phenotype in Cpt1bm-/- mice. Mice were fed either 10% fat (low fat) or 25% fat (chow) diet. Body composition was measured biweekly and indirect calorimetry was performed. Low fat diet abolishes the decreased activity, fat, and fat free mass seen in Cpt1bm-/- mice fed chow diet. Low fat diet also reduces serum myoglobin levels in Cpt1bm-/- mice and diminishes differences in IGF-1 seen between Cpt1bm-/- mice and control mice fed chow diet. Glucose tolerance tests reveal that glucose clearance is improved in Cpt1bm-/- mice relative to controls regardless of diet, and serum analysis shows increased levels of muscle derived FGF21. Electron microscopic analyses and measurements of mRNA transcripts show increased intramuscular lipids, FGF21, mitochondrial and oxidative capacity markers regardless of diet. The favorable metabolic phenotype of Cpt1bm-/- mice therefore remains consistent regardless of diet; and a combination of a low fat diet and pharmacological inhibition of CPT1b may offer remedies to reduce blood glucose.
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In carnitine palmitoyltransferase 1B knockout mice, intramyocellular lipid accumulation may not directly induce insulin resistance, but the animals exhibited muscle injury, disrupted metabolism and functional impairment that were partially ameliorated by a low-fat diet.
“A set of interesting experiments in transgenic mice (carnitine palmitoyltransferase 1B knockout) have suggested that IMCL accumulation may not directly induce insulin-resistance, but even these animals’ exhibited markers of muscle injury, disrupted metabolism and functional impairment, which were partially ameliorated by a low-fat diet [67–69].”
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [68]
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Targeting Intramyocellular Lipids to Improve Aging Muscle Function
Russ, D. W., Manickam, R., & Tipparaju, S. M. (2025) · Lipids in Health and Disease · doi:10.1186/s12944-025-02622-6 · Cited by 15 · see citing works
- Authors
- Warfel, J. D., Vandanmagsar, B., Wicks, S. E., Zhang, J., Noland, R. C., & Mynatt, R. L.
- Affiliations
- Pennington Biomedical Research Center (US)
- Corresponding author
- Mynatt, Randall L.
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-12-14
- Volume
- 12
- Issue
- 12
- Pages
- e0188850
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5730174
- OpenAlex
- W2775204416
- Cited by
- 15
- References
- 22
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 4
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK-089641, T32DK-6458413, 2P30-DK-072476-11A1)
- National Institute of General Medical Sciences (8P20GM-103528)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- carnitine palmitoyltransferase 1b, skeletal muscle, low-fat diet, high-carbohydrate diet, fat oxidation, glucose tolerance, glucose disposal, FGF21, intramuscular fat, serum myoglobin, insulin-like growth factor I, mitochondrial oxidative capacity, body composition, diabetes mellitus
- MeSH terms
- Animals, Energy Intake, Carnitine O-Palmitoyltransferase, Fatty Acids, Nonesterified, Insulin-Like Growth Factor I, Ketones, Myoglobin, Weight Gain, Mice, Knockout, Muscle, Skeletal, Diet, Fat-Restricted, Mice
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