Effects of n-3 PUFAs on postprandial variation of metalloproteinases, and inflammatory and insulin resistance parameters in dyslipidemic patients: Evaluation with euglycemic clamp and oral fat load Giuseppe Derosa, MD, PhD * , Arrigo F.G. Cicero, MD, PhD, Elena Fogari, MD, Angela D’Angelo, PhD, BD, Aldo Bonaventura, MD, Davide Romano, MD, Pamela Maffioli, MD Department of Internal Medicine and Therapeutics, University of Pavia, PAVIA, P.LE C. GOLGI, 2 – 27100 Pavia, Italy (Drs. Derosa, Fogari, D’Angelo, Bonaventura, Romano, and Maffioli); and ‘‘G. Descovich’’ Atherosclerosis Study Center, Department of Internal Medicine, Aging and Kidney Diseases, University of Bologna, Bologna, Italy (Dr. Cicero) KEYWORDS: Metalloproteinases; n-3 PUFAs; Oral fat load; Soluble intercellular adhesion molecule-1; Soluble vascular cell adhesion molecule-1; Tumor necrosis factor-a BACKGROUND: The oral fat load (OFL) is considered as one of the most accurate models of post- prandial lipoprotein metabolism and it has been widely used to evaluate the postprandial fat load effect on single markers of inflammation. OBJECTIVE: To evaluate the effects of n-3 PUFAs, primarily eicosapentaenoic acid (EPA) and do- cosahexaenoic acid (DHA), with a content of 400 mg of EPA and 450 mg of DHA in each capsule, on metalloproteinases and inflammatory biomarkers in patients affected by combined dyslipidemia both in a fasting state and after a standardized OFL in a randomized, placebo-controlled trial. METHODS: Placebo or n-3 PUFAs 3 g/day (1 g three times a day during the meals) was adminis- tered for 6 months. At the baseline, and after 2, 4, and 6 months we evaluated body mass index (BMI), body weight, fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assess- ment insulin resistance index (HOMA-IR), blood pressure, lipid profile, soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble vas- cular cell adhesion molecule-1 (sVCAM-1), sE-selectin, tumor necrosis factor-a (TNF-a), and metal- loproteinases 2 and 9 (MMP-2 and 9). Furthermore, at the baseline and at the end of the study, all patients underwent an euglycemic hyperinsulinemic clamp and an oral fat load. RESULTS: Tg levels were lower (254 mg/dL) and high-density lipoprotein cholesterol higher (16 mg/dL) with n-3 PUFAs compared with placebo; n-3 PUFAs gave lower levels of FPG (23 mg/dL), sICAM (225 ng/mL), IL-6 (20.3 pg/mL), hs-CRP (20.6 mg/L), sVCAM-1 (289 ng/mL), sE-selectin (25.8 ng/mL), TNF-a (20.3 ng/mL), MMP-2 (2185.1 ng/mL), and MMP-9 (291.5 ng/mL), and a greater M value (11.21 mmol/min/kg) compared with placebo. After the OFL, there was a decrease of Tg, MMPs, and all inflammatory parameters with n-3 PUFAs, but not with placebo. * Corresponding author. E-mail address: giuseppe.derosa@unipv.it Submitted September 2, 2011. Accepted for publication February 22, 2012. 1933-2874/$ - see front matter Ó 2012 National Lipid Association. All rights reserved. doi:10.1016/j.jacl.2012.02.010 Journal of Clinical Lipidology (2012) 6, 553–564