OBJECTIVE: Lipocalin-2 (neutrophil gelatinase-associated lipocalin, NGAL) is an innate immune system protein that has been linked to insulin resistance and obesity, but the mechanisms behind these associations are poorly known. We hypothesized that endotoxin (lipopolysaccharide, LPS) and fat intake were in the background of these associations. DESIGN: We studied four cohorts: (1) a cross-sectional study in 194 subjects; (2) the changes in NGAL concentration induced by diet and weight loss in 36 obese women (with circadian rhythm in 8 of them); (3) the effects of acute fat intake on circulating NGAL concentration in 42 morbidly obese subjects; and (4) LPS-induced NGAL secretion ex vivo (whole blood and adipose tissue explants). RESULTS: Serum NGAL concentration was significantly associated with fasting triglycerides and LPS-binding protein in patients with type 2 diabetes. In obese subjects, the intake of saturated fatty acids was the factor that best explained the variance of NGAL changes after weight loss (contributing independently to 14% of NGAL variance). In fact, weight loss significantly changed the circadian rhythm of NGAL. The acute increase in circulating NGAL after fat overload was significantly associated with fasting insulin (r=0.52, P<0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (r=0.36, P=0.02) and post-load triglyceride concentrations (r=0.38, P=0.018). LPS-induced NGAL secretion from adipose tissue explants did not change significantly, but LPS led to a significant increase in NGAL concentration in the whole blood obtained from patients with type 2 diabetes. CONCLUSION: Metabolic endotoxemia and saturated fat might contribute to circulating NGAL concentration in patients with insulin resistance.
OBJECTIVE:Lipocalin-2 (neutrophil gelatinase-associated lipocalin, NGAL) is an innate immune system protein that has been linked to insulin resistance and obesity, but the mechanisms behind these associations are poorly known. We hypothesized that endotoxin (lipopolysaccharide, LPS) and fat intake were in the background of these associations. DESIGN: We studied four cohorts: (1) a cross-sectional study in 194 subjects; (2) the changes in NGAL concentration induced by diet and weight loss in 36 obesewomen (with circadian rhythm in 8 of them); (3) the effects of acute fat intake on circulating NGAL concentration in 42 morbidly obese subjects; and (4) LPS-induced NGAL secretion ex vivo (whole blood and adipose tissue explants). RESULTS: Serum NGAL concentration was significantly associated with fasting triglycerides and LPS-binding protein in patients with type 2 diabetes. In obese subjects, the intake of saturated fatty acids was the factor that best explained the variance of NGAL changes after weight loss (contributing independently to 14% of NGAL variance). In fact, weight loss significantly changed the circadian rhythm of NGAL. The acute increase in circulating NGAL after fat overload was significantly associated with fasting insulin (r=0.52, P<0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (r=0.36, P=0.02) and post-load triglyceride concentrations (r=0.38, P=0.018). LPS-induced NGAL secretion from adipose tissue explants did not change significantly, but LPS led to a significant increase in NGAL concentration in the whole blood obtained from patients with type 2 diabetes. CONCLUSION:Metabolic endotoxemia and saturated fat might contribute to circulating NGAL concentration in patients with insulin resistance.
Authors: Joseph R Stevens; Ryan P McMillan; Justin T Resendes; Shannon K Lloyd; Mostafa M Ali; Madlyn I Frisard; Stefan Hargett; Susanna R Keller; Matthew W Hulver Journal: Metabolism Date: 2016-12-16 Impact factor: 8.694
Authors: Jacky T C Liu; Erfei Song; Aimin Xu; Thorsten Berger; Tak W Mak; Hung-Fat Tse; Ivy K M Law; Bosheng Huang; Yan Liang; Paul M Vanhoutte; Yu Wang Journal: Br J Pharmacol Date: 2012-01 Impact factor: 8.739
Authors: José M Fernández-Real; Victoria Catalán; José M Moreno-Navarrete; Javier Gómez-Ambrosi; Francisco J Ortega; Jose I Rodriguez-Hermosa; Wifredo Ricart; Gema Frühbeck Journal: Nutr Metab (Lond) Date: 2010-03-12 Impact factor: 4.169
Authors: Aleix Gavaldà-Navarro; José M Moreno-Navarrete; Tania Quesada-López; Montserrat Cairó; Marta Giralt; José M Fernández-Real; Francesc Villarroya Journal: Diabetologia Date: 2016-06-25 Impact factor: 10.122