Activation of brown adipocytes by placental growth factor

Gestational diabetes mellitus (GDM) is a type of diabetes and occurs during pregnancy. Brown adipose tissue (BAT) improves glucose homeostasis and mitigates insulin resistance, however, its activity is reduced in GDM. Placenta growth factor (PIGF) is an angiogenic factor produced by placental trophoblasts. Nevertheless, whether and how PIGF could affect BAT function in GDM are not defined. To investigate this question, 91 non-diabetic pregnant participants and 73 GDM patients were recruited to Gynaecology and Obstetrics Centre in Lu He hospital. Serum levels of PIGF were quantified by ELISA. Skin temperature was measured by far infrared thermography in the supraclavicular region where classical BATs were located. The direct effect of PIGF on BAT function was explored using the established human preadipocyte differentiation system. Thereby, we demonstrated that serum levels of PIGF were lower in GDM patients compared with controls, which was accompanied by decreased skin temperature in the supraclavicular region. By qPCR and western blot, mRNA and protein expression of UCP1 and OXPHOS were elevated in differentiated adipocytes treated with PIGF. PIGF stimulated mitochondrion transcription and increased copy number of mitochondrial. When subjected for respirometry, PIGF-treated differentiated adipocytes showed higher oxygen consumption rates than controls. PIGF induced AMPK phosphorylation and blockade of AMPK phosphorylation blunted UCP1 and OXPHOS expression in differentiated adipocytes. PIGF administration reduced cholesterol and triglyceride content in the liver and improved insulin sensitivity in db mice compared with control. In Conclusion, PIGF could activate BAT function. Downregulation of PIGF might contribute to the reduced BAT activity in GDM. (C) 2018 Published by Elsevier Inc.