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© 2019, MDPI AG. All rights reserved. Cardiotrophin-1 (CT-1) is a gp130 cytokine that was previously characterized for its e ects on cardiomyocytes and identified as a marker of heart failure. More recent studies reported elevated circulating levels of CT-1 in humans with obesity and metabolic syndrome (MetS). However, a subsequent rodent study implicated CT-1 as a potential therapeutic target for obesity and MetS. Adipose tissue (AT) is broadly acknowledged as an endocrine organ and is a substantial source of CT-1. However, no study has examined the expression of adipose-derived CT-1 in humans. We present the first analysis of CT-1 mRNA expression in subcutaneous AT and its association with clinical variables in 22 women with obesity and 15 men who were 40% overfed for 8-weeks. We observed that CT-1 expression was higher in the subcutaneous abdominal (scABD) than the femoral (scFEM) depot. Importantly, we reveal that scFEM but not scABD, CT-1 expression was negatively associated with visceral adiposity and intrahepatic lipid, while positively correlated with insulin sensitivity in obese women. Also, men with higher CT-1 levels at baseline had less of a decline in insulin sensitivity in response to overfeeding. Our data provide new knowledge on the regulation of adipose-derived CT-1 in obesity and during weight gain in response to overfeeding in humans and suggest that CT-1 may play a protective role in obesity and related disorders.

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