Lipocalin-2 increases fat oxidation in vitro and is correlated with energy expenditure in normal weight but not obese women.

Abstract

The role of lipocalin-2 (Lcn2) was determined in regulating metabolism in cell, animal, and human models. Adipocytes were treated with recombinant lipocalin-2 (rLcn2) to determine the effect on lipid metabolism. rLcn2 was injected into mice to determine the effect on metabolism in vivo. To assess the relationship between Lcn2 and fat oxidation (FatOx) in humans, normal weight (NW) and obese (OB) women were given three separate high fat (HF) meals followed by indirect calorimetry. The relationship between postprandial Lcn2 with macronutrient metabolism and total energy expenditure (TEE) using Pearson correlations was determined. Lcn2 increased expression of genes involved in β-oxidation including peroxisome proliferator-activated receptor-δ in adipocytes, as well as (3) H labeled oleate β-oxidation. Lcn2 injected into chow-fed mice directly increased TEE by 18% after the first dark cycle (232 ± 1.4 cal vs. 341 ± 1.4 cal; PBS vs. Lcn2) and remained significantly elevated by 10% after the second dark cycle (296 ± 1.4 cal vs. 326 ± 1.4 cal; PBS vs. Lcn2). Lcn2 was correlated with TEE in all three HF meal challenges in NW but not OB females. Lipocalin-2 is a novel adipokine that promotes FatOx and TEE and its function may be impaired in obesity.