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Overproduction of large VLDL particles is driven by increased liver fat content in man
Open accessAbstract
Aims/hypothesis We determined whether hepatic fat content and plasma adiponectin concentration regulate VLDL(1) production.Methods A multicompartment model was used to simultaneously determine the kinetic parameters of triglycerides (TGs) and apolipoprotein B (ApoB) in VLDL(1) and VLDL(2) after a bolus of [(2)H(3)]leucine and [(2)H(5)]glycerol in ten men with type 2 diabetes and in 18 non-diabetic men. Liver fat content was determined by proton spectroscopy and intra-abdominal fat content by MRI.Results Univariate regression analysis showed that liver fat content, intra-abdominal fat volume, plasma glucose, insulin and HOMA-IR (homeostasis model assessment of insulin resistance) correlated with VLDL(1) TG and ApoB production. However, only liver fat and plasma glucose were significant in multiple regression models, emphasising the critical role of substrate fluxes and lipid availability in the liver as the driving force for overproduction of VLDL(1) in subjects with type 2 diabetes. Despite negative correlations with fasting TG levels, liver fat content, and VLDL(1) TG and ApoB pool sizes, adiponectin was not linked to VLDL(1) TG or ApoB production and thus was not a predictor of VLDL(1) production. However, adiponectin correlated negatively with the removal rates of VLDL(1) TG and ApoB.Conclusions/interpretation We propose that the metabolic effect of insulin resistance, partly mediated by depressed plasma adiponectin levels, increases fatty acid flux from adipose tissue to the liver and induces the accumulation of fat in the liver. Elevated plasma glucose can further increase hepatic fat content through multiple pathways, resulting in overproduction of VLDL(1) particles and leading to the characteristic dyslipidaemia associated with type 2 diabetes.
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“data from metabolic studies conducted on human subjects (3,4) indicate that an increase in VAT is associated with impaired glucose tolerance, insulin resistance, and increased very-low-density lipoproteintriglyceride (VLDL-TG) secretion.”
From Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity (2009) · cites this paper as [3]
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“and suggest the commonly observed relationship between increased VAT and metabolic disease (1-4) is because of the correlation between VAT and IHTG (8)(9)(10).”
From Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity (2009) · cites this paper as [3]
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Metadata
- Authors
- Adiels, M., Taskinen, M.-R., Packard, C., Caslake, M. J., Soro-Paavonen, A., Westerbacka, J., Vehkavaara, S., Häkkinen, A., Olofsson, S.-O., Yki-Järvinen, H., & Borén, J.
- Affiliations
- University of Gothenburg (SE)
- University of Helsinki (FI)
- Glasgow Royal Infirmary (GB)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Borén, J.
- Venue
- Diabetologia
- Published
- 2006-02-04
- Volume
- 49
- Issue
- 4
- Pages
- 755-765
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2051999166
- Cited by
- 690
- References
- 53
- Citations by year
- 2026: 15 · 2025: 26 · 2024: 29 · 2023: 21 · 2022: 35 · 2021: 29 · 2020: 40 · 2019: 31 · 2018: 27 · 2017: 27 · 2016: 37 · 2015: 41 · 2014: 41 · 2013: 45 · 2012: 38
- FWCI
- 26.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Chalmers Research (Chalmers University of Technology) (submittedVersion)
- Funders
- Helsingin ja Uudenmaan Sairaanhoitopiiri
- Göran Gustafssons Stiftelser
- Hjärt-Lungfonden
- Vetenskapsrådet
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- hepatic fat content, adiponectin, apolipoprotein B, triglyceride kinetics, type 2 diabetes, insulin resistance, intra-abdominal fat, dyslipidemia
- MeSH terms
- Adipose Tissue, Adult, Aged, Apolipoproteins B, Diabetes Mellitus, Type 2, Fatty Liver, Humans, Lipoproteins, VLDL, Male, Middle Aged
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