Plasma Lactoferrin Levels Positively Correlate with Insulin Resistance despite an Inverse Association with Total Adiposity in Lean and Severely Obese Patients

CONTEXT: Lactoferrin (Lf) is an important protein found on mucosal surfaces, within neutrophils and various cells, and in biological fluids. It displays multiple functions, including iron-binding as well as antimicrobial, immunomodulatory and anti-inflammatory activities. Although Lf ingestion has been suggested to cause adiposity reduction in murine models and humans, its relationship with insulin resistance (IR) has not been studied thoroughly. OBJECTIVE: To establish the association between circulating Lf levels, glucose status and blood lipid/lipoprotein profile. METHODS: Two independent cohorts were examined: lean to moderately obese women admitted for gynecological surgery (n = 53) and severely obese subjects undergoing biliopancreatic diversion (n = 62). RESULTS: Although body mass index (BMI) and total body fat mass were negatively associated with Lf, IR (assessed by the HOMA-IR index) was positively and independently associated with plasma Lf concentrations of the first cohort of lean to moderately obese women. These observations were validated in the second cohort in view of the positive correlation between plasma Lf concentrations and the HOMA-IR index, but without a significant association with the body mass index (BMI) of severely obese subjects. In subsamples of severely obese subjects matched for sex, age and BMI, but with either relatively low (1.89 ± 0.73) or high (13.77 ± 8.81) IR states (according to HOMA-IR), higher plasma Lf levels were noted in insulin-resistant vs insulin-sensitive subjects (P<0.05). Finally, Lf levels were significantly higher in lean to moderately obese women than in severely obese subjects (P<0.05). CONCLUSION: Our findings revealed that plasma Lf levels are strongly associated with IR independently of total adiposity, which suggests an intriguing Lf regulation mechanism in conditions of obesity and IR.