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Atherogenic subfractions of lipoproteins in the treatment of metabolic syndrome by physical activity and diet – the RESOLVE trial

Frédéric Dutheil1234, Guillaume Walther5, Robert Chapier1, George Mnatzaganian6, Bruno Lesourd17, Geraldine Naughton2*, Julien Verney1, Anne Fogli8, Vincent Sapin8, Martine Duclos3, Agnès Vinet5, Philippe Obert5, Daniel Courteix12 and Gérard Lac1

Author Affiliations

1 Laboratory of Metabolic Adaptations to Exercise in Physiological and Pathological conditions (AME2P, EA3533), Blaise Pascal University, Clermont-Ferrand, France

2 School of Exercise Science, Australian Catholic University, East Melbourne, VIC, Australia

3 Sport Medicine and Functional Exploration, University Hospital CHU G. Montpied, Clermont-Ferrand, France

4 Occupational Medicine, University Hospital CHU G. Montpied, Clermont-Ferrand, France

5 Laboratory of Pharm-Ecology Cardiovascular (EA4278), Avignon, France

6 Faculty of Health Sciences, Australian Catholic University, East Melbourne, VIC, Australia

7 Geriatrics, Faculty of Medicine, Clermont-Ferrand, France

8 Biochemistry, University Hospital CHU G. Montpied, Clermont-Ferrand, France

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Lipids in Health and Disease 2014, 13:112  doi:10.1186/1476-511X-13-112

Published: 11 July 2014



We aimed to comprehensively evaluate lipoprotein profile including lipid particle size following a lifestyle intervention in metabolic syndrome (MetS) volunteers and to assess the associations between lipoprotein subfractions and carotid-intima-media-thickness (CIMT) – a surrogate indicator of atherogenesis.


100 participants (50–70 years) from the RESOLVE trial, underwent a one-year follow-up beginning with a three-week residential program combining high exercise volume (15-20 h/week), restrictive diet (-500 kcal/day), and education. For baseline references, 40 aged-matched healthy controls were recruited. Independent associations between subfractions of lipoproteins and CIMT were evaluated using a generalized estimating equations model accounting for variation in correlations between repeated measures. The lipoprotein subfractions profile was assessed using Lipoprint® electrophoresis allowing to separate: the very low-density lipoprotein (VLDL) fraction, then the intermediate-density lipoprotein (IDL) C, B and A, the low-density lipoprotein (LDL) with subfractions 1 and 2 as large LDL and subfractions 3 to 7 as small dense LDL (sdLDL), and the high density lipoprotein (HDL) subfractions categorized into large, intermediate, and small HDL. Apolipoproteins A1 and B were also measured.


78 participants completed the program. At baseline, apolipoproteins B/A1, VLDL, sdLDL and small HDL were higher in MetS than in healthy controls; IDL, LDL size, large and intermediate HDL were lower. Despite time-related regains during the follow-up, lipoprotein subfractions traditionally involved in cardiovascular risk, such as sdLDL, improved immediately after the residential program with values closest to those of healthy controls. CIMT improved throughout the lifestyle intervention. Using a generalized estimating equations model, none of the subfractions of lipoproteins nor apolipoproteins were linked to CIMT.


Lipoprotein subfractions traditionally involved in CVR, decreased after the 3-week residential program. During a 12 month follow-up, the time-related regains remained closer to the values of healthy controls than they were at baseline. CIMT improved throughout the lifestyle intervention. However, we failed to demonstrate a link between some lipoprotein subfractions and the atherogenicity directly measured from the wall thickness of arteries (CIMT). Further investigations are required to explore the atherogenicity of lipoprotein subfractions.

Trial registration


Metabolic syndrome; Obesity; Cardiovascular risk; Framingham; Physical activity; Diet; Nutrition; Apolipoproteins