Serum secreted EMC10 (scEMC10) levels are inversely associated with metabolically active brown adipose tissue in humans

Abstract

Background/Objectives: Secreted endoplasmic reticulum membrane complex subunit 10 (scEMC10) has been implicated in obesity in mice and humans. In this study, the associations of serum scEMC10 levels with thermoneutrality-modulated brown adipose tissue (BAT) activity and thyroid hormone (TH)-dependent thermogenesis were investigated in humans. Subjects/Methods: Serum scEMC10 levels were measured in participants from manifold cohorts using enzyme-linked immunosorbent assay, including participants with or without active BAT determined by PET-CT scanning, BAT-positive participants before and after thermoneutrality, and patients with hyperthyroidism before and after an anti-thyroid drug treatment. The difference in serum scEMC10 between BAT-positive and -negative participants, and the changes of serum scEMC10 in BAT-positive participants before and after thermoneutrality and in patients with Grave’s disease-caused hyperthyroidism before and after an anti-thyroid drug (ATD) treatment were determined. Results: ¹⁸F-FDG PET–CT scanning indicated BAT-positive participants were significantly younger and leaner than BAT-negative ones. There was, however, no significant difference in serum scEMC10 between the two groups. Serum scEMC10 levels in BAT-positive participants were significantly elevated by 2-hour thermoneutrality (P = 0.0017), concomitant with disappearance of active BAT. No significant association of serum scEMC10 with serum levels of either TSH, FT3, or FT4 was observed in participants from both Chinese and White cohorts. ATD treatment normalized thyroid function and reduced the uptake of ¹⁸F-FDG in skeletal muscle of patients with hyperthyroidism. Serum scEMC10 concentration, however, remained unchanged in these patients before and after ATD treatment. Conclusions: Serum scEMC10 levels are inversely associated with metabolically active BAT, suggesting scEMC10 a suppressive role in facultative thermogenesis in humans. This finding implicates inhibition of scEMC10 in the treatment of obesity and its associated cardiometabolic diseases.