Role of Dietary Fats in Modulating Cardiometabolic Risk During Moderate Weight Gain: A Randomized Double‐Blind Overfeeding Trial (LIPOGAIN Study)

BACKGROUND: Whether the type of dietary fat could alter cardiometabolic responses to a hypercaloric diet is unknown. In addition, subclinical cardiometabolic consequences of moderate weight gain require further study. METHODS AND RESULTS: In a 7‐week, double‐blind, parallel‐group, randomized controlled trial, 39 healthy, lean individuals (mean age of 27±4) consumed muffins (51% of energy [%E] from fat and 44%E refined carbohydrates) providing 750 kcal/day added to their habitual diets. All muffins had identical contents, except for type of fat; sunflower oil rich in polyunsaturated fatty acids (PUFA diet) or palm oil rich in saturated fatty acids (SFA diet). Despite comparable weight gain in the 2 groups, total: high‐density lipoprotein (HDL) cholesterol, low‐density lipoprotein:HDL cholesterol, and apolipoprotein B:AI ratios decreased during the PUFA versus the SFA diet (−0.37±0.59 versus +0.07±0.29, −0.31±0.49 versus +0.05±0.28, and −0.07±0.11 versus +0.01±0.07, P=0.003, P=0.007, and P=0.01 for between‐group differences), whereas no significant differences were observed for other cardiometabolic risk markers. In the whole group (ie, independently of fat type), body weight increased (+2.2%, P<0.001) together with increased plasma proinsulin (+21%, P=0.007), insulin (+17%, P=0.003), proprotein convertase subtilisin/kexin type 9, (+9%, P=0.008) fibroblast growth factor‐21 (+31%, P=0.04), endothelial markers vascular cell adhesion molecule–1, intercellular adhesion molecule–1, and E‐selectin (+9, +5, and +10%, respectively, P<0.01 for all), whereas nonesterified fatty acids decreased (−28%, P=0.001). CONCLUSIONS: Excess energy from PUFA versus SFA reduces atherogenic lipoproteins. Modest weight gain in young individuals induces hyperproinsulinemia and increases biomarkers of endothelial dysfunction, effects that may be partly outweighed by the lipid‐lowering effects of PUFA. CLINICAL TRIAL REGISTRATION: URL: http://ClinicalTrials.gov. Unique identifier: NCT01427140.