title: Perinatal overnutrition exacerbates adipose tissue inflammation caused by high-fat feeding in C57BL/6J mice.
abstract: Obesity causes white adipose tissue (WAT) inflammation and insulin resistance in some, but not all individuals. Here, we used a mouse model of early postnatal overfeeding to determine the role of neonatal nutrition in lifelong WAT inflammation and metabolic dysfunction. C57BL/6J mice were reared in small litters of 3 (SL) or normal litters of 7 pups (NL) and fed either regular chow or a 60% high fat diet (HFD) from 5 to 17 weeks. At weaning, SL mice did not develop WAT inflammation despite increased fat mass, although there was an up-regulation of WAT Arg1 and Tlr4 expression. On HFD, adult SL mice had greater inguinal fat mass compared to NL mice, however both groups showed similar increases in visceral fat depots and adipocyte hypertrophy. Despite the similar levels of visceral adiposity, SL-HFD mice displayed greater impairments in glucose homeostasis and more pronounced hepatic steatosis compared to NL-HFD mice. In addition, WAT from SL mice fed a HFD displayed greater crown-like structure formation, increased M1 macrophages, and higher cytokine gene expression. Together, these data suggest that early postnatal overnutrition may be a critical determinant of fatty liver and insulin resistance in obese adults by programming the inflammatory capacity of adipose tissue.
authors.affiliation: Human and Evolutionary Biology Program, Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California, United States of America; Department of Preventive Medicine, Keck School of Medicine, Childhood Obesity Research Center, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Brandon D
authors.initials: BD
authors.lastname: Kayser
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, Childhood Obesity Research Center, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Goran
authors.affiliation: Developmental Neuroscience Program, The Saban Research Institute, Children's Hospital Los Angeles, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Sebastien G
authors.initials: SG
authors.lastname: Bouret
mesh_terms: D050154:Adiposity; D000818:Animals; D001835:Body Weight; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism; D044343:Overnutrition; D050177:Overweight; D015434:Panniculitis / Q000209:etiology* / Q000378:metabolism
chemical_list: D005947:Glucose
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