title: Postnatal overfeeding promotes early onset and exaggeration of high-fat diet-induced nonalcoholic fatty liver disease through disordered hepatic lipid metabolism in rats.
abstract: Exposure to overnutrition in critical or sensitive developmental periods may increase the risk of developing obesity and metabolic syndrome in adults. Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, but the relationship among postnatal nutrition, lipid metabolism, and NAFLD progression during development remains poorly understood. Here we investigated in a rat model whether postnatal overfeeding increases susceptibility to NAFLD in response to a high-fat diet. Litters from Sprague-Dawley dams were culled to three (small litters) or ten (normal litters) pups and then weaned onto a standard or high-fat diet at postnatal day 21 to generate normal-litter, small-litter, normal-litter/high-fat, and small-litter/high-fat groups. At age 16 weeks, the small-litter and both high-fat groups showed obesity, dyslipidemia, and insulin resistance. Hepatic disorders appeared earlier in the small-litter/high-fat rats with greater liver mass gain and higher hepatic triglycerides and steatosis score versus normal-litter/high-fat rats. Hepatic acetyl-CoA carboxylase activity and mRNA expression were increased in small-litter rats and aggravated in small-litter/high-fat rats but not in normal-litter/high-fat rats. The high expression in small-litter/high-fat rats coincided with high sterol regulatory element-binding protein-1c mRNA and protein expression. However, mRNA expression of enzymes involved in hepatic fatty acid oxidation (carnitine palmitoyltransferase 1) and output (microsomal triglyceride transfer protein) was decreased under a high-fat diet regardless of litter size. In conclusion, overfeeding related to small-litter rearing during lactation contributes to the NAFLD phenotype when combined with a high-fat diet, possibly through up-regulated hepatic lipogenesis.
authors.affiliation: Department of Children Health Care, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Chenlin
authors.initials: C
authors.lastname: Ji
authors.affiliation: Department of Children Health Care, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Neonatal Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Children Health Care, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Children Health Care, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Hou
authors.affiliation: Department of Clinical Laboratory, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Junle
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Burén
authors.affiliation: Department of Children Health Care, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China; Institute of Pediatric Research, Nanjing Medical University, Nanjing, China. Electronic address: xnli@njmu.edu.cn.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D001835:Body Weight; D017931:DNA Primers; D059305:Diet, High-Fat; D050356:Lipid Metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology*; D009929:Organ Size; D044343:Overnutrition; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers
keywords: Early overfeeding; High-fat diet; Lipid metabolism; Liver; Nonalcoholic fatty liver disease; Rat