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Fatty Acid Desaturase Activities in Metabolic Syndrome and Cardiovascular Disease: Special Reference to Stearoyl-CoA-Desaturase and Biomarkers of Dietary Fat
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The development of the metabolic syndrome (MetS) and cardiovascular diseases have been suggested to be influenced more by the quality than the amount of dietary fat. The FA composition of serum lipids may be used as biomarkers of dietary fat quality. FAs can, however, also be endogenously synthesized by lipogenic enzymes such as elongases and desaturases. Three desaturases are important in humans: Stearoyl-CoA-desaturase (SCD), ∆6-desaturase (D6D) and ∆5-desaturase (D5D) and surrogate measures of desaturase activities can be estimated as product-to-precursor FA ratios.

In this thesis, we demonstrated that high SCD, D6D and low D5D estimated activities predicted MetS 20 years later, as well as cardiovascular and total mortality during a maximum of 33.7 years. The relation between D5D and MetS was independent of lifestyle and BMI, while the relation between SCD, D6D and MetS was confounded by BMI. Serum proportions of palmitic (16:0), palmitoleic (16:1) and dihomo-γ-linoleic acids were higher and the serum proportion of linoleic acid (LA) lower at baseline in those individuals who developed MetS. Further, LA was inversely related to mortality, while palmitic, palmitoleic and dihomo-γ-linoleic acids were directly associated with mortality. We also demonstrated that a diet rich in saturated fat “induced” a similar serum FA pattern (including estimated desaturase activities) that was associated with MetS, cardiovascular disease and mortality. We also propose that the SCD ratio [16:1/16:0] might be a novel and useful marker of dietary saturated fat, at least in Western high-fat diets. Finally, genetic variations in the human SCD1 gene were linked to obesity and insulin sensitivity, results that agree with data in SCD1 deficient mice.

This thesis suggests that dietary fat quality and endogenous desaturation may play a role in the development of metabolic and cardiovascular diseases and the results support current dietary guidelines.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2007. , p. 77
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 292
Keywords [en]
Nutrition, Fatty acids, Dietary fat, Biomarker, Metabolic Syndrome, Mortality, Obesity, Insulin Sensitivity, Epidemiology, Estimated desaturase activities, Stearoyl-CoA-desaturase, delta-6-desaturase, delta-5-desaturase, Single Nucleotide Polymorphism, Dietary Intervention, Rapeseed oil, Saturated fat, SCD1
Keywords [sv]
Näringslära
Identifiers
URN: urn:nbn:se:uu:diva-8312ISBN: 978-91-554-7025-8 (print)OAI: oai:DiVA.org:uu-8312DiVA, id: diva2:171034
Public defence
2007-12-07, IV, Universitetshuset, Uppsala, 09:15
Opponent
Supervisors
Available from: 2007-11-16 Created: 2007-11-16Bibliographically approved
List of papers
1. Fatty acid composition of serum lipids predicts the development of the metabolic syndrome in men
Open this publication in new window or tab >>Fatty acid composition of serum lipids predicts the development of the metabolic syndrome in men
2005 In: Diabetologia, ISSN 0012-186X (Print), Vol. 48, no 10, p. 1999-2005Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-96453 (URN)
Available from: 2007-11-16 Created: 2007-11-16Bibliographically approved
2. Serum Fatty Acid Composition as a Predictor of Total and Cardiovascular Mortality: A Population-Based Prospective Study in Men
Open this publication in new window or tab >>Serum Fatty Acid Composition as a Predictor of Total and Cardiovascular Mortality: A Population-Based Prospective Study in Men
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Article in journal (Refereed) Submitted
Identifiers
urn:nbn:se:uu:diva-96454 (URN)
Available from: 2007-11-16 Created: 2007-11-16Bibliographically approved
3. Polymorphisms in the SCD1 gene: associations with body fat distribution and insulin sensitivity
Open this publication in new window or tab >>Polymorphisms in the SCD1 gene: associations with body fat distribution and insulin sensitivity
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2007 (English)In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 15, no 7, p. 1732-1740Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE:

Obesity and insulin resistance are major risk factors for metabolic diseases and are influenced by lifestyle and genetics. The lipogenic enzyme, stearoyl-coenzyme A-desaturase (SCD), is related to obesity. Further, SCD1-deficent mice are protected against obesity and insulin resistance. We hypothesized that genetic polymorphisms in the SCD1 gene would be associated with obesity, insulin sensitivity, and estimated SCD activity in humans.

RESEARCH METHODS AND PROCEDURES:

The study population was 1143 elderly Swedish men taking part of a population-based cohort study, the Uppsala Longitudinal Study of Adult Men. Associations between single nucleotide polymorphisms and obesity (waist circumference and BMI), insulin sensitivity (assessed by hyperinsulinemic euglycemic clamp), and estimated SCD activity (fatty acid ratios) were analyzed using linear regression analysis.

RESULTS:

Subjects homozygous for the rare alleles of rs10883463, rs7849, rs2167444, and rs508384 had decreased BMI and waist circumference and improved insulin sensitivity. The rare allele of rs7849 demonstrated the strongest effect on both insulin sensitivity [regression coefficient (beta)=1.19, p=0.007] and waist circumference (beta=-4.4, p=0.028), corresponding to 23% higher insulin sensitivity and 4 cm less waist circumference.

CONCLUSION:

This study indicates that genetic variations in the SCD1 gene are associated with body fat distribution and insulin sensitivity, results that accord well with animal data. These results need confirmation in other populations with a larger sample size.

Keywords
stearoyl-coenzyme A-desaturase, waist circumference, insulin sensitivity, single-nucleotide polymorphism
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-96455 (URN)10.1038/oby.2007.206 (DOI)000248242900014 ()
Available from: 2007-11-16 Created: 2007-11-16 Last updated: 2017-12-14Bibliographically approved
4. Effects of saturated and unsaturated fatty acids on estimated desaturase activities during a controlled dietary intervention
Open this publication in new window or tab >>Effects of saturated and unsaturated fatty acids on estimated desaturase activities during a controlled dietary intervention
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2008 (English)In: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 18, no 10, p. 683-690Article in journal (Refereed) Published
Abstract [en]

Background and aims

Direct measurement of desaturase activities are difficult to obtain in humans. Consequently, surrogate measures of desaturase activity (estimated desaturase activities) have been frequently used in observational studies, and estimated Δ9- (or stearoyl-CoA-desaturase (SCD)), Δ6- and Δ5-desaturase activities have been associated with cardiometabolic disease. Data on how the markers of desaturase activities are modified by changes in dietary fat quality are lacking and therefore warrant examination.

Methods and results

In a two-period (three weeks) strictly controlled cross-over study, 20 subjects (six women and 14 men) consumed a diet high in saturated fat (SAT-diet) and a rapeseed oil diet (RO-diet), rich in oleic acid (OA), linoleic acid (LA) and α-linolenic acid (ALA). Estimated desaturase activities were calculated as precursor to product FA ratios in serum cholesteryl esters and phospholipids. The estimated SCD [16:1 n-7/16:0] and Δ6-desaturase [20:3 n-6/18:2 n-6] was significantly higher while Δ5-desaturase [20:4 n-6/20:3 n-6] was significantly lower in the SAT-diet (P<0.001 for all), compared to the RO-diet. The serum proportions of palmitic, stearic, palmitoleic and dihomo-γ-linolenic acids were significantly higher in the SAT-diet while the proportions of LA and ALA were significantly higher in the RO-diet.

Conclusion

This is the first study to demonstrate that surrogate measures of desaturase activities change as a consequence of an alteration in dietary fat quality. Both the [16:1/16:0]-ratio and 16:1 seem to reflect changes in saturated fat intake and may be useful markers of saturated fat intake in Western countries.

Keywords
Fatty acid composition, Stearoyl-CoA-desaturase, Δ6-Desaturase, Δ5-Desaturase, Dietary fat quality, Estimated desaturase activities
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-96456 (URN)10.1016/j.numecd.2007.11.002 (DOI)000262609500007 ()18367385 (PubMedID)
Available from: 2007-11-16 Created: 2007-11-16 Last updated: 2017-12-14Bibliographically approved

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