Fat Overload Induces Changes in Circulating Lactoferrin That Are Associated With Postprandial Lipemia and Oxidative Stress in Severely Obese Subjects

Lactoferrin is an innate immune system protein with anti-inflammatory and antioxidant activities. We aimed to evaluate circulating lactoferrin levels in association with lipid concentrations, and parameters of oxidative stress and inflammation in subjects with morbid obesity after an acute fat intake. The effects of a 60 g fat overload on circulating lactoferrin and antioxidant activities were evaluated in 45 severely obese patients (15 men and 30 women, BMI 53.4 +/- 7.2 kg/m(2)). The change in circulating lactoferrin after fat overload was significantly and inversely associated with the free fatty acid (FFA) change. In those subjects with the highest increase in lactoferrin (in the highest quartile), high-density lipoprotein (HDL)-cholesterol decreased after fat overload to a lesser extent (P = 0.03). In parallel to lipid changes, circulating lactoferrin concentrations were inversely linked to the variations in catalase (CAT) and glutathione reductase (GSH-Rd). Baseline circulating lactoferrin concentration was also inversely associated with the absolute change in antioxidant activity after fat overload, and with the change in C-reactive protein (CRP). Furthermore, those subjects with higher than the median value of homeostasis model assessment of insulin secretion (HOMA(IS)) had significantly increased lactoferrin concentration after fat load (885 +/- 262 vs. 700 +/- 286 ng/ml, P = 0.03). Finally, we further explored the action of lactoferrin in vitro. Lactoferrin (10 mu mol/l) led to significantly lower triglyceride (TG) concentrations and lactate dehydrogenase activity (as expression of cell viability) in the media from adipose explants obtained from severely obese subjects. In conclusion, circulating lactoferrin concentrations, both at baseline and fat-stimulated, were inversely associated with postprandial lipemia, and parameters of oxidative stress and fat-induced inflammation in severely obese subjects.