Impact of adrenomedullin on mitochondrial respiratory capacity in human adipocyte.

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.

Impact of Adrenomedullin on Mitochondrial Respiratory Capacity in Human Adipocyte.

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.

Maternal low protein diet and fetal programming of lean type 2 diabetes.

Maternal nutrition is found to be the key factor that determines fetal health and metabolic health during adulthood. Metabolic diseases have been primarily attributed to impaired maternal nutrition during pregnancy, and impaired nutrition has been an immense issue across the globe. In recent years, type 2 diabetes (T2D) has reached epidemic proportion and is a severe public health problem in many countries.

In utero low-protein-diet-programmed type 2 diabetes in adult offspring is mediated by sex hormones in rats†.

Sex steroids regulate insulin sensitivity and glucose metabolism. We had characterized a lean type 2 diabetes (T2D) rat model using gestational low-protein (LP) diet programming. Our objective was to identify if endocrine dysfunction leading to decreased sex hormone levels will precede the development of T2D and if steroid replacement will prevent the onset of the disease.