Endocrine Abstracts

Background: In an obese state, pro-inflammatory adipokines can lead to mitochondrial dysfunction and reduced brown adipocytes properties in white adipocytes (BRITE adipocytes), all of which contribute to the pathogenesis of obesity and type 2 diabetes mellitus (T2DM). A recent novel adipokine, asprosin, that influences appetite and glucose homeostasis, appears to drive inflammation in obesity. However, asprosin expression in human adipose tissue (AT) depots, its impact on mitochondria, and the browning process is unknown, which this study sought to investigate.

Methods: Human abdominal (Abd) subcutaneous (Sc) and Abd omental (Om) AT paired biopsies were collected (female; age: 31.6±6.1Yr; BMI: 27.9±5.9Kg/m²; n = 126) in an ethically approved study. RNA was extracted from AbdAT (lean: n = 43 lean, overweight: n = 47, obese: n = 36, subjects) and asprosin, mitochondrial, BRITE and inflammatory gene expression was quantified by qRT-PCR. Mitochondrial function analysis was undertaken using Seahorse Analyzer to measure oxygen consumption rate (OCR).

Results: Asprosin was readily expressed in both abdominal depots. Obesity reduced asprosin mRNA expression in AbdScAT (obese: 11.4%↓P < 0.01) but not in AbdOmAT (obese; P = N.S). In AbdScAT, increased asprosin expression positively correlated with mitochondrial biogenesis (PRC: P < 0.001; NRF1: P < 0.05), but led to a reduction in mitochondria function (COX4: P < 0.0001↓), mitochondrial fusion (MFN2: P < 0.0001↓), and a rise in oxidative damage (SOD2: P = 0 .0287↑) and inflammation (MCP1: P < 0.05↑). Rising asprosin mRNA expression also led to BRITE gene reduction (CIDEA: P < 0.01↓; ELOVL3: P = 0 .0144↓; PLIN5: P < 0.01↓). In AbdOmAT, asprosin had less impact on mitochondrial and browning genes. Asprosin treatment also influenced AbdSc adipocyte OCR.

Conclusions: In summary, asprosin was predominately associated with mitochondrial dysfunction and reduced BRITE phenotype in AbdScAT, whilst the influence on AbdOmAT was minimal. Taken together, these data suggest that raised systemic asprosin levels in obese subjects would further damage critical AbdSc (rather than AbdOm) adipocyte function, to increase their metabolic disease risk.