Endocrine Abstracts

Background: Lipocalin 2 (NGAL) is considered a pro-inflammatory adipokine. Noting the conflicting reports as to the role of Lipocalin 2 in metabolic disease, it remains unclear whether an acute or chronic state affects its impact on adipocyte function. In an attempt to address this our current studies investigated for the first time in humans, whether Lipocalin 2 in abdominal subcutaneous adipose tissue (AT) may influence mitochondrial function and browning of adipocytes, as contributing mechanisms of obesity mediated type 2 diabetes mellitus (T2DM) disease.

Methods: Human abdominal subcutaneous (AbdSc) AT biopsies were collected (female; 31.6± 5.6 Yr, BMI: 27.8± 5.8 Kg/m², n = 125) in an ethically approved study. RNA was extracted from AbdScAT (lean: age: 32.3± 5.2Yr, BMI: 22.2± 1.9 Kg/m², n = 43; overweight: age: 31.06± 5.8Yr, BMI: 27.5± 1.3Kg/m², n = 46; Obese; age: 31.2± 5.8Yr, BMI: 35± 4.6Kg/m², n = 36) and gene expression quantified by qRT-PCR. Lipocalin 2, asprosin, mitochondrial, BRITE, and inflammatory genes were assessed.

Results: Lipocalin 2 mRNA expression in AbdScAT, increased mitochondrial biogenesis (PRC P < 0.05), but led to a reduction in mitochondrial function (COX4: P < 0.0001↓) and mitochondrial fusion (MFN2: P < 0.0001↓; OPA1: P < 0.05↓). Rising Lipocalin 2 mRNA expression also led to reduced browning gene expression (CIDEA: P < 0.05↓; ELOVL3: P = 0 .05↓; PLIN5: P < 0.05↓) in AbdScAT. Lipocalin 2 did not appear influenced by adiposity, insulin or HOMA-IR. Lipocalin 2 was also positively correlated with the adipokine asprosin (P < 0.0001).

Conclusions: In summary, Lipocalin 2 was associated with mitochondrial impairment, impacting mitochondrial dynamics, and a reduced browning phenotype in AbdScAT. These data therefore suggest that raised systemic lipocalin 2 levels in obese or T2DM subjects, may act as a secondary mediator or a biomarker of damage to critical adipocyte mitochondrial function, rather than the protagonist in inducing metabolic disease risk.