Impaired Fat Oxidation After a Single High-Fat Meal in Insulin-Sensitive Nondiabetic Individuals With a Family History of Type 2 Diabetes
Open accessAbstract
Individuals with insulin resistance and type 2 diabetes have an impaired ability to switch appropriately between carbohydrate and fatty acid oxidation. However, whether this is a cause or consequence of insulin resistance is unclear, and the mechanism(s) involved in this response is not completely elucidated. Whole-body fat oxidation and transcriptional regulation of genes involved in lipid metabolism in skeletal muscle were measured after a prolonged fast and after consumption of either high-fat (76%) or high-carbohydrate (76%) meals in individuals with no family history of type 2 diabetes (control, n = 8) and in age- and fatness-matched individuals with a strong family history of type 2 diabetes (n = 9). Vastus lateralis muscle biopsies were performed before and 3 h after each meal. Insulin sensitivity and fasting measures of fat oxidation were not different between groups. However, subjects with a family history of type 2 diabetes had an impaired ability to increase fatty acid oxidation in response to the high-fat meal (P < 0.05). This was related to impaired activation of genes involved in lipid metabolism, including those for peroxisome proliferator–activated receptor coactivator-1α (PGC1α) and fatty acid translocase (FAT)/CD36 (P < 0.05). Of interest, adiponectin receptor-1 expression decreased 23% after the high-fat meal in both groups, but it was not changed after the high-carbohydrate meal. In conclusion, an impaired ability to increase fatty acid oxidation precedes the development of insulin resistance in genetically susceptible individuals. PGC1α and FAT/CD36 are likely candidates in mediating this response.
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Prior work indicates that in insulin-resistant states, lipid oxidation is impaired at a given circulating NEFA concentration, i.e., MetFlex-lip is impaired.
“Therefore, previous studies demonstrate that insulin-resistant states have impaired lipid oxidation for a certain circulating NEFA level, i.e., impaired MetFlex-lip.”
From Metabolic flexibility to lipid availability during exercise is enhanced in individuals with high insulin sensitivity (2018) · cites this paper as [15]
Likewise, healthy individuals with a family history of T2D had normal NEFA increases but lower lipid oxidation (15).
“Similarly, healthy subjects with a family history of T2D showed normal increases in circulating NEFA but reduced lipid oxidation (15).”
From Metabolic flexibility to lipid availability during exercise is enhanced in individuals with high insulin sensitivity (2018) · cites this paper as [15]
In response to a high-carbohydrate meal, individuals with a family history of diabetes had a higher plasma insulin concentration and a similar increase in RQ compared with control subjects.
“However, in response to a high-carbohydrate meal (1,000 kcal, 76% energy from carbohydrate), individuals with a family history of diabetes had a higher plasma insulin concentration and a similar increase in RQ compared with control subjects.”
From Metabolic flexibility and insulin resistance (2008) · cites this paper as [20]
The lower reliance on fat oxidation for energy supply in offspring from diabetic parents suggests that impaired fat oxidation might precede insulin resistance.
“The lower reliance on fat oxidation for energy supply in offspring from diabetic parents suggests that impaired fat oxidation might precede insulin resistance.”
From Metabolic flexibility and insulin resistance (2008) · cites this paper as [20]
After a high-fat meal, individuals without a family history of diabetes had a larger decrease in RQ compared with offspring from diabetic parents.
“In both groups, the changes in plasma glucose, FFA, and insulin concentrations were similar; however, individuals without a history of diabetes had larger decrease in RQ compared with offspring from diabetic parents.”
From Metabolic flexibility and insulin resistance (2008) · cites this paper as [20]
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Metabolic flexibility and insulin resistance
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- Authors
- Heilbronn, L. K., Gregersen, S., Shirkhedkar, D., Hu, D., & Campbell, L. V.
- Affiliations
- Garvan Institute of Medical Research (AU)
- Aarhus University Hospital (DK)
- Diabetes and Obesity Program, Garvan Institute of Medical Research, New South Wales, Australia
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2007-08-01
- Volume
- 56
- Issue
- 8
- Pages
- 2046-2053
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2115446050
- Cited by
- 70
- References
- 50
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 8 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 1 · 2015: 8 · 2014: 3 · 2013: 5 · 2012: 4
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- Medical Research Council
- National Health and Medical Research Council
- National Medical Research Council
- 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 › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- fat oxidation, high-fat meal, insulin sensitivity, type 2 diabetes risk, family history of type 2 diabetes, skeletal muscle lipid metabolism, PGC-1α, FAT/CD36, AdipoR1, insulin resistance, genetic susceptibility
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Adult, Biopsy, Diabetes Mellitus, Type 2, Dietary Fats, Fats, Female, Gene Expression Regulation, Health, Heat-Shock Proteins, Humans, Insulin, Male, Oxidation-Reduction, Pedigree, Transcription Factors, Muscle, Skeletal, CD36 Antigens, Thermogenesis
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