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Tissue-specific stable isotope measurements of postprandial lipid metabolism in familial combined hyperlipidaemia

Tissue-specific stable isotope measurements of postprandial lipid metabolism in familial combined hyperlipidaemia
Tissue-specific stable isotope measurements of postprandial lipid metabolism in familial combined hyperlipidaemia
Objective: The metabolic defects underlying familial combined hyperlipidaemia (FCHL) are not clearly understood. We used stable isotope techniques combined with tissue-specific measurements in adipose tissue and forearm muscle to investigate fatty acid handling by these tissues in the fasting and postprandial states.

Results: Patients were insulin resistant as shown by higher glucose and insulin concentrations and lower muscle glucose extraction than controls. Plasma triacylglycerol (TAG) concentrations were higher in patients. Adipose tissue TAG extraction was not lower in patients than controls, although TAG clearance was lower, probably representing saturation. Following a test meal, patients showed a greater increase in chylomicron-TAG concentrations. There were no differences between FCHL patients and controls in postprandial suppression of non-esterified fatty acid (NEFA) concentrations or postprandial NEFA release, but patients had greater trapping of exogenous fatty acids in adipose tissue. 3-Hydroxybutyrate concentrations were lower in patients indicative of decreased hepatic fatty acid oxidation.

Conclusions: In this group of patients with FCHL, the major defect appeared to be overproduction of TAG by the liver due to decreased fatty acid oxidation, with fatty acids directed to TAG synthesis. We found no evidence of decreased lipoprotein lipase action or impaired fatty acid re-esterification in adipose tissue
adipose-tissue, vldl, middle aged, cholesterol, insulin, humans, fatty acids, female, blood glucose, research, diagnostic use, liver, esterification, fasting, apolipoproteins b, male, adult, glucose, nonesterified, diagnosis, regional blood flow, muscle, fatty acid, chemistry, lipid metabolism, chylomicrons, metabolism, 3-hydroxybutyric acid, postprandial period, adipose tissue, plasma, hyperlipidemia, carbon isotopes, familial combined, blood, acid
0021-9150
164-170
Evans, Kevin
5a8ae844-c282-45fc-9def-dd52db4a8eb1
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Wootton, Stephen A.
bf47ef35-0b33-4edb-a2b0-ceda5c475c0c
Collins, Jenny M.
f5409ea6-69cf-40bc-ab56-0474b7b97cc8
Clark, Mo L.
58267bbc-37c4-4eae-8026-7ef83a59113f
Tan, Garry D.
1c089c08-9ef2-484e-b12b-3c9ba28e479b
Karpe, Frederik
bf68a56d-a95c-4159-85fc-e0d7e2b1d627
Frayn, Keith N.
43ece647-8996-45ba-a004-2c921f2d3ca4
Evans, Kevin
5a8ae844-c282-45fc-9def-dd52db4a8eb1
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Wootton, Stephen A.
bf47ef35-0b33-4edb-a2b0-ceda5c475c0c
Collins, Jenny M.
f5409ea6-69cf-40bc-ab56-0474b7b97cc8
Clark, Mo L.
58267bbc-37c4-4eae-8026-7ef83a59113f
Tan, Garry D.
1c089c08-9ef2-484e-b12b-3c9ba28e479b
Karpe, Frederik
bf68a56d-a95c-4159-85fc-e0d7e2b1d627
Frayn, Keith N.
43ece647-8996-45ba-a004-2c921f2d3ca4

Evans, Kevin, Burdge, Graham C., Wootton, Stephen A., Collins, Jenny M., Clark, Mo L., Tan, Garry D., Karpe, Frederik and Frayn, Keith N. (2008) Tissue-specific stable isotope measurements of postprandial lipid metabolism in familial combined hyperlipidaemia. Atherosclerosis, 197 (1), 164-170. (doi:10.1016/j.atherosclerosis.2007.03.009). (PMID:17466309)

Record type: Article

Abstract

Objective: The metabolic defects underlying familial combined hyperlipidaemia (FCHL) are not clearly understood. We used stable isotope techniques combined with tissue-specific measurements in adipose tissue and forearm muscle to investigate fatty acid handling by these tissues in the fasting and postprandial states.

Results: Patients were insulin resistant as shown by higher glucose and insulin concentrations and lower muscle glucose extraction than controls. Plasma triacylglycerol (TAG) concentrations were higher in patients. Adipose tissue TAG extraction was not lower in patients than controls, although TAG clearance was lower, probably representing saturation. Following a test meal, patients showed a greater increase in chylomicron-TAG concentrations. There were no differences between FCHL patients and controls in postprandial suppression of non-esterified fatty acid (NEFA) concentrations or postprandial NEFA release, but patients had greater trapping of exogenous fatty acids in adipose tissue. 3-Hydroxybutyrate concentrations were lower in patients indicative of decreased hepatic fatty acid oxidation.

Conclusions: In this group of patients with FCHL, the major defect appeared to be overproduction of TAG by the liver due to decreased fatty acid oxidation, with fatty acids directed to TAG synthesis. We found no evidence of decreased lipoprotein lipase action or impaired fatty acid re-esterification in adipose tissue

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More information

e-pub ahead of print date: 26 April 2007
Published date: March 2008
Keywords: adipose-tissue, vldl, middle aged, cholesterol, insulin, humans, fatty acids, female, blood glucose, research, diagnostic use, liver, esterification, fasting, apolipoproteins b, male, adult, glucose, nonesterified, diagnosis, regional blood flow, muscle, fatty acid, chemistry, lipid metabolism, chylomicrons, metabolism, 3-hydroxybutyric acid, postprandial period, adipose tissue, plasma, hyperlipidemia, carbon isotopes, familial combined, blood, acid

Identifiers

Local EPrints ID: 61105
URI: http://eprints.soton.ac.uk/id/eprint/61105
ISSN: 0021-9150
PURE UUID: cab1bed0-bfe8-4401-9f62-6409b8135d6f
ORCID for Graham C. Burdge: ORCID iD orcid.org/0000-0002-7665-2967

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Date deposited: 02 Sep 2008
Last modified: 15 Mar 2024 11:22

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Contributors

Author: Kevin Evans
Author: Jenny M. Collins
Author: Mo L. Clark
Author: Garry D. Tan
Author: Frederik Karpe
Author: Keith N. Frayn

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