Publication Date
6-13-2023
Journal
Scientific Reports
DOI
10.1038/s41598-023-36622-2
PMID
37311963
PMCID
PMC10264416
PubMedCentral® Posted Date
6-13-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Female, Humans, Pregnancy, Adipocytes, Adrenomedullin, Cytochromes b, Diabetes, Gestational, DNA, Mitochondrial, Glucose, Lipids, Mitochondria, RNA, Messenger
Abstract
Mitochondrial function in adipocyte is an important aspect in maintaining metabolic homeostasis. 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), 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. The present study demonstrated that: (1) Increasing doses of glucose and ADM inhibit human adipocyte mRNA expressions of mitochondrial DNA (mtDNA)-encoded subunits of electron transport chain, 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 generation and this increase is reversed by ADM antagonist, ADM22-52, but treatment with ADM does not significantly affect mitochondrial contents in the adipocytes; (3) Adipocyte basal and maximal oxygen consumption rate are dose-dependently suppressed by ADM, thus results in impaired mitochondrial respiratory capacity. We conclude that elevated ADM observed in diabetic pregnancy may be involved in glucose and lipid dysregulation through compromising adipocyte mitochondrial function, and blockade of ADM action may improve GDM-related glucose and adipose tissue dysfunction.