title: Multiparity leads to obesity and inflammation in mothers and obesity in male offspring.
abstract: Multiparity is an independent risk factor for obesity in parous females. In addition to being a health issue for the mother, offspring of multiparous females may also be at risk for obesity later in life. The aim of the current study was to establish a mouse model that mimics the human pathology of multiparity and determine the effects of multiparity-induced obesity (MIO) on offspring in adulthood. C57BL/6 mice were mated and studied when primiparous (1st pregnancy) or multiparous (4th pregnancy). Dams became obese with multiparity, an effect that was independent of the age of the dam. Multiparous dams also had increased markers of inflammation (JNK activation, cytokine expression) in adipose tissue and liver that was greater than inflammation in nulliparous females made obese with a high-fat diet. Placental inflammation was prevalent in multiparous vs. primiparous dams as well. Male offspring of the multiparous dams developed increased adiposity by 24 wk of age relative to the progeny of primiparous dams, although food consumption was similar in both groups. Lipid metabolism was altered in liver and fat in that mRNA levels of regulatory genes (PGC-1α) as well as metabolic genes (CPT I) and Akt phosphorylation were decreased in offspring of multiparous dams. Thus, in mice, as in humans, multiparity increases adiposity and is associated with hepatic and placental inflammation and abnormal glucose tolerance. Importantly, MIO leads to increased body fat and metabolic dysfunction in the offspring, suggesting a role in the propagation of obesity.
authors: Department of Pathology and Laboratory Medicine, University of Cincinnati Medical School, Cincinnati, OH 45237-0507, USA.
authors: Sandra L
authors: SL
authors: Rebholz
authors: Thomas
authors: T
authors: Jones
authors: Katie T
authors: KT
authors: Burke
authors: Anja
authors: A
authors: Jaeschke
authors: Patrick
authors: P
authors: Tso
authors: David A
authors: DA
authors: D'Alessio
authors: Laura A
authors: LA
authors: Woollett
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D050154:Adiposity; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D059305:Diet, High-Fat; D004435:Eating; D005260:Female; D007249:Inflammation / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009765:Obesity / Q000378:metabolism*; D010298:Parity; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis; D014157:Transcription Factors
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D002334:Carnitine O-Palmitoyltransferase; D051057:Proto-Oncogene Proteins c-akt