Impact of Adrenomedullin on Mitochondrial Respiratory Capacity in Human Adipocyte

Abstract

Abstract For metabolic homeostasis adequate mitochondrial function in adipocytes is essential. Our previous observation showed that circulating levels of adrenomedullin (ADM) and mRNA and protein for ADM in omental adipose tissue were higher in patients with gestational diabetes mellitus (GDM) compared with normal pregnancy, and these alterations are accompanied by glucose and lipid metabolic dysregulation, but the impact of ADM on mitochondrial biogenesis and respiration in human adipocyte remain elusive. In this study we demonstrated that: (1) Increasing doses of glucose and ADM inhibit human adipocyte mRNA expressions of mitochondrial DNA (mtDNA)-encoded subunits of electron transport chain (ETC), including nicotinamide adenine dinucleotide dehydrogenase (ND) 1 and 2, cytochrome (CYT) b, as well as ATPase 6; (2) ADM significantly increases human adipocyte mitochondrial reactive oxygen species (ROS) generation and this increase is reversed by ADM antagonist, ADM22-52, but does not significantly affect adipocyte mitochondrial contents; (3) Adipocyte basal and maximal oxygen consumption rate (OCR) are dose-dependently suppressed by ADM, and results in impaired mitochondrial respiratory capacity. We conclude that elevatedADM observed in diabetic pregnancy may be involved in glucose and lipid dysregulation through compromising adipocyte mitochondrial function, and blockade of ADM actions in adipocytes may improve GDM-related metabolic complications.