Maternal obesity leads to increased proliferation and numbers of astrocytes in the developing fetal and neonatal mouse hypothalamus.
Maternal obesity during pregnancy is associated with chronic maternal, placental, and fetal inflammation; and it elevates the risk for offspring obesity. Changes in the development of the hypothalamus, a brain region that regulates body weight and energy balance, are emerging as important determinants of offspring risk, but such changes are only beginning to be defined. Here we focused on the hypothesis that the pathological exposure of developing hypothalamic astrocytes to cytokines would alter their development. A maternal high-fat diet (mHFD) mouse model was used to investigate changes in hypothalamic astrocytes in the fetus during late gestation and in early neonates by using immunochemistry, confocal microscopy, and qPCR. The number of astrocytes and the proportion of proliferating astrocytes was significantly higher in the arcuate nucleus (ARC) and the supraoptic nucleus (SON) of the hypothalamus at both ages compared to control offspring from normal weight pregnancies. Supplemental to this we found that cultured fetal hypothalamic astrocytes proliferated significantly in response to IL6 (10ng/ml), one of the cytokines significantly elevated in fetuses of obese dams, via the JAK/STAT3 signaling pathway. Thus, maternal obesity during pregnancy stimulated the proliferation and thereby increased numbers of astrocytes in the fetal as well as early neonatal hypothalamus, which may be driven, during fetal life, by IL6.
Centre for Neuroendocrinology, Department of Anatomy, University of Otago School of Medical Sciences, Dunedin, New Zealand.
Dong Won
DW
Kim
Centre for Neuroendocrinology, Department of Anatomy, University of Otago School of Medical Sciences, Dunedin, New Zealand.
Kelly A
KA
Glendining
Centre for Neuroendocrinology, Department of Anatomy, University of Otago School of Medical Sciences, Dunedin, New Zealand.
David R
DR
Grattan
Centre for Neuroendocrinology, Department of Anatomy, University of Otago School of Medical Sciences, Dunedin, New Zealand. Electronic address: christine.jasoni@anatomy.otago.ac.nz.
Christine L
CL
Jasoni
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001835:Body Weight; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D047109:Fetal Development / Q000187:drug effects / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007031:Hypothalamus / Q000196:embryology* / Q000473:pathology*; D015850:Interleukin-6 / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D051058:Oncogene Protein v-akt; D001973:Bromodeoxyuridine
Arcuate nucleus; Developmental programming; Inflammation; Neurodevelopment; pSTAT3