Increasing skeletal muscle fatty acid transport protein 1 (FATP1) targets fatty acids to oxidation and does not predispose mice to diet-induced insulin resistance
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Aims/hypothesis We examined in skeletal muscle (1) whether fatty acid transport protein (FATP) 1 channels long-chain fatty acid (LCFA) to specific metabolic fates in rats; and (2) whether FATP1-mediated increases in LCFA uptake exacerbate the development of diet-induced insulin resistance in mice. We also examined whether FATP1 is altered in insulin-resistant obese Zucker rats.Methods LCFA uptake, oxidation and triacylglycerol esterification rates were measured in control and Fatp1-transfected soleus muscles to determine FATP1-mediated lipid handling. The effects of FATP1 on insulin sensitivity and triacylglycerol accumulation were determined in high-fat diet-fed wild-type mice and in muscle-specific Fatp1 (also known as Slc27a1) overexpressing transgenic mice driven by the muscle creatine kinase (Mck [also known as Ckm]) promoter. We also examined the relationship between FATP1 and both fatty acid transport and metabolism in insulin-resistant obese Zucker rats.Results Transient Fatp1 overexpression in soleus muscle increased (p < 0.05) palmitate transport (24%) and oxidation (35%), without altering triacylglycerol esterification or the intrinsic rate of palmitate oxidation in isolated mitochondria. In Mck/Fatp1 animals, Fatp1 mRNA and 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid uptake in skeletal muscle were upregulated (75%). However, insulin sensitivity and intramuscular triacylglycerol content did not differ between wild-type and Mck/Fatp1 mice following a 16 week high-fat diet. In insulin-resistant obese Zucker rats, LCFA transport and triacylglycerol accumulation were increased (85% and 24%, respectively), but this was not attributable to Fatp1 expression, as neither total cellular nor sarcolemmal FATP1 content were altered.Conclusions/interpretation Overexpression of Fatp1 in skeletal muscle increased the rate of LCFA transport and channelled these lipids to oxidation, not to intramuscular lipid accumulation. Therefore, skeletal muscle FATP1 overabundance does not predispose animals to diet-induced insulin resistance.
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Besides hyperlipidaemia-induced ectopic lipid deposition, dysregulated lipid oxidation in mitochondria during ageing also predisposes individuals to muscle IR.
“Besides hyperlipidaemia‐induced ectopic lipid deposition, dysregulated lipid oxidation in mitochondria during ageing also predisposes individuals to muscle IR.[ 53 ]”
From Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review (2022) · cites this paper as [53]
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Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review
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- Authors
- Holloway, G. P., Chou, C. J., Lally, J., Stellingwerff, T., Maher, A. C., Gavrilova, O., Haluzik, M., Alkhateeb, H., Reitman, M. L., & Bonen, A.
- Affiliations
- University of Guelph (CA)
- National Institutes of Health (US)
- Nestlé (Switzerland) (CH)
- Hashemite University (JO)
- Corresponding author
- Holloway, G. P.
- Venue
- Diabetologia
- Published
- 2011-03-26
- Volume
- 54
- Issue
- 6
- Pages
- 1457-1467
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2026644276
- Cited by
- 54
- References
- 47
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 6 · 2013: 4 · 2012: 5
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- FATP1, SLC27A1, skeletal muscle, long-chain fatty acid transport, fatty acid oxidation, palmitate uptake, triacylglycerol esterification, insulin resistance, high-fat diet, Zucker fatty rats, mitochondrial fatty acid oxidation
- MeSH terms
- Animals, Dietary Fats, Disease Models, Animal, Fatty Acids, Female, Insulin Resistance, Mice, Transgenic, Mitochondria, Muscle, Obesity, Oxidation-Reduction, Palmitates, Rats, Zucker, Triglycerides, Rats, Sprague-Dawley, Muscle, Skeletal, Fatty Acid Transport Proteins, Mice, Rats
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