Upregulation of Lipocalin 2 in Adipose Tissues of Severely Obese Women: Positive Relationship With Proinflammatory Cytokines

Abstract

Because the role of lipocalin 2 (LCN2) in morbid obesity is still not well defined, the aim of this study was to evaluate the circulating levels and the expression of LCN2 in visceral (VAT) and subcutaneous adipose tissue (SAT) in severely obese (SO) women. We also analyzed its relationship with inflammatory cytokines in the same subjects. The study comprised 90 white women, 39 of whom were lean controls (BMI ≤25 kg/m2) and 51 SO (BMI ≥40 kg/m2). Both circulating and adipose tissue levels of LCN2 were quantified by enzyme‐linked immunosorbent assays. LCN2 mRNA levels from VAT and SAT were assessed by real‐time reverse transcriptase‐PCR (n = 60). LCN2 serum levels were significantly higher in the SO women than in the lean controls (P = 0.042), and were found to be strongly correlated with tumor necrosis factor receptor I (TNFR1) circulating levels. In the SO cohort, LCN2 serum levels were also associated with higher BMI values, but not with the homeostasis model assessments of insulin resistance (HOMA2‐IR). LCN2 mRNA expression was markedly higher in SO women than in lean women in both VAT (P = 0.043) and SAT (P = 0.031). In SAT, LCN2 was negatively correlated with adiponectin and adiponectin receptor‐2 expression, and positively with interleukin‐6 (IL‐6) expression. A strong positive correlation was also found between LCN2 expression and the mean diameter of adipocytes in VAT. Our results revealed that the circulating level of LCN2 is associated with obesity and BMI. LCN2 mRNA is over‐expressed in adipose tissue from SO subjects. Finally, the expression of LCN2 is strongly related to an expression profile of proinflammatory cytokines but not to insulin resistance in nondiabetic SO women.

Podwyższone stężenia lipokaliny-2 w surowicy krwi są związane ze wskaźnikami metabolizmu glukozy i metabolizmu kostnego w przebiegu cukrzycy typu 2

“…Since BMI and sex have been shown to be related to serum LCN2 levels in human, the subjects in the NGT group who had no statistical differences in those parameters compared to T2DM group were chosen as controls in this study [14,20]. A number of factors correlating to serum LCN2 levels have been identified in the past decade, including lung injury, kidney injury, pancreatic injury, and cardiovascular disease [3,5,21,22].…”

“…A recent study also indicated that LCN2 levels were elevated in obese women and could be used as an early predictor of T2DM [13]. Nevertheless, no significant association of LCN2 with HOMA-IR was indicated in non-diabetic obese women [14].…”

Neutrophil Gelatinase–Associated Lipocalin, a Novel Mineralocorticoid Biotarget, Mediates Vascular Profibrotic Effects of Mineralocorticoids

“…7 At difference to rodents, human Lcn2/NGAL has a cysteine residue at position 87 allowing a dissulfide bond with matrix metalloproteinase 9 (MMP-9) 8 that stabilizes MMP-9, increasing its activity. 9,10 In clinical studies, increased Lcn2/NGAL concentrations have been reported in obese patients [11][12][13] a population prone to develop both hyperaldosteronism and HF. [14][15][16] We took advantage of a previously characterized human cohort of asymptomatic obese subjects but as such prone to develop CVDs, including HF, to question whether Lcn2/ NGAL is correlated with plasma aldosterone levels and markers of extracellular matrix (ECM) remodeling.…”

Adipokines – Toward the Molecular Dissection of Interactions Between Stromal Adipocytes and Breast Cancer Cells

“…This protein structurally belongs to the lipocalin superfamily that shares the highly conserved structure of an 8-stranded antiparallel beta-barrel . Circulating level of lipocalin-2 is elevated in obese animals and humans (Auguet et al 2011;Hoo et al 2008;Wang et al 2007a;Yan et al 2007;Zhang et al 2008). Clinical, animal and cellular studies demonstrate the causal involvement of lipocalin-2 in obesity-associated medical complications (Auguet et al 2011;Catalan et al 2009;Esteve et al 2009;Jin et al 2010;Kanaka-Gantenbein et al 2008;Law et al 2010;Moreno-Navarrete et al 2010;Sommer et al 2009;van Dam and Hu 2007;Yan et al 2007;Zhang et al 2008).…”

“…Circulating level of lipocalin-2 is elevated in obese animals and humans (Auguet et al 2011;Hoo et al 2008;Wang et al 2007a;Yan et al 2007;Zhang et al 2008). Clinical, animal and cellular studies demonstrate the causal involvement of lipocalin-2 in obesity-associated medical complications (Auguet et al 2011;Catalan et al 2009;Esteve et al 2009;Jin et al 2010;Kanaka-Gantenbein et al 2008;Law et al 2010;Moreno-Navarrete et al 2010;Sommer et al 2009;van Dam and Hu 2007;Yan et al 2007;Zhang et al 2008). In humans, the serum concentration of lipocalin-2 is associated closely with obesity-related anthropometric and biochemical variables, and represents an independent risk factor for metabolic and cardiovascular disorders (Catalan et al 2009;Choi et al 2008;Ding et al 2010;Esteve et al 2009;Hemdahl et al 2006;Lee et al 2010;Wang et al 2007a;Yndestad et al 2009).…”