J Clin Lipidol. 2014 Jul-Aug;8(4):408-17.

Effects of bariatric surgery on HDL structure and functionality: results from a prospective trial.

Zvintzou E, Skroubis G, Chroni A, Petropoulou PI, Gkolfinopoulou C, Sakellaropoulos G, Gantz D, Mihou I, Kalfarentzos F, Kypreos KE.

Pharmacology Department, University of Patras Medical School, Rio Achaias, TK26500, Greece




In addition to high-density lipoprotein cholesterol (HDL-C) levels, HDL quality appears also very important for atheroprotection. Obese patients with metabolic syndrome have significantly reduced HDL-C levels and are usually at increased risk for coronary heart disease. Despite that weight loss benefits these patients, its effects on HDL quality and functionality is currently poorly studied.


We investigated how rapid weight loss affects HDL structure and its antioxidant potential in patients undergoing a malabsorptive bariatric procedure.


Fasting plasma samples were collected the day before and 6 months after the bariatric procedure from 20 morbidly obese patients with body mass index >50, then HDL was isolated and analyzed by biochemical techniques.


We report a dramatic alteration in the apolipoprotein ratio of HDL that was accompanied by the presence of more mature HDL subspecies and a concomitant increase in the antioxidant potential of HDL. Interestingly, our obese cohort could be distinguished into 2 subgroups. In 35% of patients (n = 7), HDL before surgery had barely detectable apolipoprotein (apo) A-I and apoCIII, and the vast majority of their HDL cholesterol was packed in apoE-containing HDL particles. In the remaining 65% of patients (n = 13), HDL before surgery contained high levels of apoA-I and apoCIII, in addition to apoE. In both subgroups, surgical weight loss resulted in a switch from apoE to apoA-I-containing HDL.


Rapid weight loss exerts a significant improvement in HDL structure and functionality that may contribute to the documented beneficial effect of malabsorptive bariatric procedures on cardiovascular health.

PMID: 25110222



It is customary in the literature to refer to HDL as cholesterol rather than what it really is: a population of lipoprotein particles that are heterogeneous in size and apolipoprotein composition, where variations in apolipoprotein content of these particles sets the basis for functional heterogeneity of HDL between individuals (1). The inverse correlation between HDL-cholesterol (HDL-C) levels and coronary risk, initially reported by John Gofman (2) and Richard Havel (3), and later confirmed in the Framingham Heart Study (4), led to the principle that high HDL-C levels in plasma protect from atherosclerosis. However, more recent data reinforced the principle of “HDL quality” in atherosclerosis, that refers to the functionality of HDL particle, as defined by its protein and lipid content (5) rather than plasma HDL-C levels alone. Based on this modern principle, to assess the beneficial impact of HDL to a single individual, it is very important to first understand how genes, proteins, and lipids affect HDL functions.

To this date there is only very limited information on how HDL composition affects its functionality. To better understand this relationship, recently we turned our attention to relevant clinical examples. One such example is rapid weight loss following bariatric surgery that is associated with a reduced risk for coronary heart disease later on in life (6). Following analysis of HDL particle composition we found that rapid weight loss was associated with a significant switch from a primarily apolipoprotein E (apoE)- and apoliporpotein CIII (apoCIII)-containing HDL to a primarily apolipoprotein A-I (apoA-I)-containing HDL. This compositional change was associated with a significant improvement of the antioxidant properties of HDL. Concomitantly, we observed a significant improvement of the plasma enzymatic activity signature of lecithin:cholesterol acyltransferase and cholesterylester transfer protein. Our data may also explain a puzzling observation associated with malabsorptive bariatric interventions that is, patient’s HDL-C levels show a decline immediately after the operation and then start rising to preoperative levels within the first six months (7;8). Our data show that this initial drop in HDL-C levels reflects a gradual qualitative switch of HDL from apoE- and apoCIII-containing HDL to apoA-I-containing HDL, with a parallel increase in HDL particle functionality.




Figure 1. The ApoE/ApoA-I and ApoCIII/apoA-I ratios of HDL are surrogate biomarkers of HDL functionality. Only low ratios allow HDL to be functional and turn the HDL-mobile into healthy town. High ratios set HDL dysfunctional and send HDL-mobile to CHD town.


Importance of the study:

Our data indicate that the apoA-I/apoE and apoA-I/apoCIII concentration ratios of HDL are surrogate biomarkers of HDL functionality in atheroprotection and should have a far more powerful predictive value than plasma HDL-C levels alone. However, no clinical recommendation can be made before this statement is further validated in a prospective clinical trial and the physiological values for these ratios are defined in the general healthy population.



This work was executed within the framework of the Action «Excellence» (Project No. 241) of the Operational Program “Education and Lifelong Learning” (Action’s Beneficiary: General Secretariat for Research and Technology), and is co-financed by the European Social Fund (ESF) and the Greek State. The Morbid Obesity Unit of the Department of Surgery at the University of Patras has been accredited as a Center of Excellence from the European Chapter of the International Federation for the Surgery of Obesity (IFSO).



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 Kyriakos_Kypreos copy Contact: Kyriakos E. Kypreos

Professor of Pharmacology and Chairman

University of Patras

School of Health Sciences

Department of Medicine

Pharmacology Laboratory


TK. 26500, Rio Achaias





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