Corin Deficiency Alters Adipose Tissue Phenotype and Impairs Thermogenesis in Mice

SIMPLE SUMMARY: Thermoregulation is of fundamental significance for all endothermic animals. Corin is a protease that activates atrial natriuretic peptide (ANP), a cardiac hormone critical in cardiovascular homeostasis and adipose tissue function. In this study, we report that in mice, corin deficiency increased the weight and cell size in white adipose tissue, decreased thermogenic gene profiles in brown adipose tissue, and impaired thermogenic responses upon cold exposure, leading to hypothermia. In brown adipose tissue from corin-deficient mice, the ANP-mediated p38 mitogen-activated protein kinase and uncoupling protein 1 signaling mechanism is compromised. These findings indicate a crucial role of corin in modulating adipose tissue function and thermogenesis upon cold exposure in mice. ABSTRACT: Atrial natriuretic peptide (ANP) is a key regulator in body fluid balance and cardiovascular biology. In addition to its role in enhancing natriuresis and vasodilation, ANP increases lipolysis and thermogenesis in adipose tissue. Corin is a protease responsible for ANP activation. It remains unknown if corin has a role in regulating adipose tissue function. Here, we examined adipose tissue morphology and function in corin knockout (KO) mice. We observed increased weights and cell sizes in white adipose tissue (WAT), decreased levels of uncoupling protein 1 (Ucp1), a brown adipocyte marker in WAT and brown adipose tissue (BAT), and suppressed thermogenic gene expression in BAT from corin KO mice. At regular room temperature, corin KO and wild-type mice had similar metabolic rates. Upon cold exposure at 4 °C, corin KO mice exhibited impaired thermogenic responses and developed hypothermia. In BAT from corin KO mice, the signaling pathway of p38 mitogen-activated protein kinase, peroxisome proliferator-activated receptor c coactivator 1a, and Ucp1 was impaired. In cell culture, ANP treatment increased Ucp1 expression in BAT-derived adipocytes from corin KO mice. These data indicate that corin mediated-ANP activation is an important hormonal mechanism in regulating adipose tissue function and body temperature upon cold exposure in mice.