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Variation in the promoter of the human hormone sensitive lipase gene shows gender specific effects on insulin and lipid levels: results from the Ely study

Variation in the promoter of the human hormone sensitive lipase gene shows gender specific effects on insulin and lipid levels: results from the Ely study
Variation in the promoter of the human hormone sensitive lipase gene shows gender specific effects on insulin and lipid levels: results from the Ely study
We previously identified a hormone sensitive lipase (HSL) promoter variant, ?60C>G, which in vitro exhibits 40% reduced promoter activity. In this study we examined the effect of the ?60C>G on glycemic and lipid measures in the population based Ely study of metabolic function and insulin resistance in 218 middle-aged men and 276 middle-aged women. Adipose tissue HSL is the rate-limiting step in triglyceride lipolysis, generating free fatty acids for energy utilization. HSL is also expressed in pancreatic ?-cells where its activity therefore may affect insulin secretion. In the women, carriers of the HSL ?60G allele had significantly lower fasting insulin levels (P=0.0005) and a lower total area under the curve for insulin during the oral glucose tolerance test (P=0.005). There was no demonstrable association in men with these measures of insulin sensitivity but carriers of the ?60G allele had significantly lower fasting non-esterified fatty acid (NEFA) levels (P=0.025) and higher low density lipoprotein cholesterol levels (P=0.02) than men who were non-carriers. This study provides additional evidence for a role for HSL in the development of insulin resistance, from which carriers of the ?60G allele, associated here with markers of insulin sensitivity in women, and with lower NEFA levels in men, might be protected.
hormone sensitive lipase, insulin resistance, fasting insulin levels, genetic polymorphism
0925-4439
239-244
Talmud, Philippa J.
6beee2db-2839-4ea3-8f1f-7b08c8d7b550
Palmen, Jutta
76470af3-40ed-4d3f-afb4-2c8c1d712ae1
Luan, Jian'an
c6f1b3b4-947f-4ac5-9fef-63dfe2b1bbdd
Flavell, Dave
4566cc2d-6d2a-459c-a593-b84193933387
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Waterworth, Dawn M.
1a110a48-1069-4678-a67e-f8f6ea24a662
Wareham, Nicholas J.
bbc18cd9-3512-4ca6-806c-75c9a01e5adf
Talmud, Philippa J.
6beee2db-2839-4ea3-8f1f-7b08c8d7b550
Palmen, Jutta
76470af3-40ed-4d3f-afb4-2c8c1d712ae1
Luan, Jian'an
c6f1b3b4-947f-4ac5-9fef-63dfe2b1bbdd
Flavell, Dave
4566cc2d-6d2a-459c-a593-b84193933387
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Waterworth, Dawn M.
1a110a48-1069-4678-a67e-f8f6ea24a662
Wareham, Nicholas J.
bbc18cd9-3512-4ca6-806c-75c9a01e5adf

Talmud, Philippa J., Palmen, Jutta, Luan, Jian'an, Flavell, Dave, Byrne, Christopher D., Waterworth, Dawn M. and Wareham, Nicholas J. (2001) Variation in the promoter of the human hormone sensitive lipase gene shows gender specific effects on insulin and lipid levels: results from the Ely study. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1537 (3), 239-244. (doi:10.1016/S0925-4439(01)00076-X).

Record type: Article

Abstract

We previously identified a hormone sensitive lipase (HSL) promoter variant, ?60C>G, which in vitro exhibits 40% reduced promoter activity. In this study we examined the effect of the ?60C>G on glycemic and lipid measures in the population based Ely study of metabolic function and insulin resistance in 218 middle-aged men and 276 middle-aged women. Adipose tissue HSL is the rate-limiting step in triglyceride lipolysis, generating free fatty acids for energy utilization. HSL is also expressed in pancreatic ?-cells where its activity therefore may affect insulin secretion. In the women, carriers of the HSL ?60G allele had significantly lower fasting insulin levels (P=0.0005) and a lower total area under the curve for insulin during the oral glucose tolerance test (P=0.005). There was no demonstrable association in men with these measures of insulin sensitivity but carriers of the ?60G allele had significantly lower fasting non-esterified fatty acid (NEFA) levels (P=0.025) and higher low density lipoprotein cholesterol levels (P=0.02) than men who were non-carriers. This study provides additional evidence for a role for HSL in the development of insulin resistance, from which carriers of the ?60G allele, associated here with markers of insulin sensitivity in women, and with lower NEFA levels in men, might be protected.

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More information

Published date: 2001
Keywords: hormone sensitive lipase, insulin resistance, fasting insulin levels, genetic polymorphism

Identifiers

Local EPrints ID: 26011
URI: http://eprints.soton.ac.uk/id/eprint/26011
ISSN: 0925-4439
PURE UUID: c25ea886-8be0-4a59-a2d8-a05f9273c8ea
ORCID for Christopher D. Byrne: ORCID iD orcid.org/0000-0001-6322-7753

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Date deposited: 21 Apr 2006
Last modified: 16 Mar 2024 03:07

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Contributors

Author: Philippa J. Talmud
Author: Jutta Palmen
Author: Jian'an Luan
Author: Dave Flavell
Author: Dawn M. Waterworth
Author: Nicholas J. Wareham

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