title: Neonatal overnutrition in mice exacerbates high-fat diet-induced metabolic perturbations.
abstract: Neonatal overnutrition results in accelerated development of high-fat diet (HFD)-induced metabolic defects in adulthood. To understand whether the increased susceptibility was associated with aggravated inflammation and dysregulated lipid metabolism, we studied metabolic changes and insulin signaling in a chronic postnatal overnutrition (CPO) mouse model. Male Swiss Webster pups were raised with either three pups per litter to induce CPO or ten pups per litter as control (CTR) and weaned to either low-fat diet (LFD) or HFD. All animals were killed on the postnatal day 150 (P150) except for a subset of mice killed on P15 for the measurement of stomach weight and milk composition. CPO mice exhibited accelerated body weight gain and increased body fat mass prior to weaning and the difference persisted into adulthood under conditions of both LFD and HFD. As adults, insulin signaling was more severely impaired in epididymal white adipose tissue (WAT) from HFD-fed CPO (CPO-HFD) mice. In addition, HFD-induced upregulation of pro-inflammatory cytokines was exaggerated in CPO-HFD mice. Consistent with greater inflammation, CPO-HFD mice showed more severe macrophage infiltration than HFD-fed CTR (CTR-HFD) mice. Furthermore, when compared with CTR-HFD mice, CPO-HFD mice exhibited reduced levels of several lipogenic enzymes in WAT and excess intramyocellular lipid accumulation. These data indicate that neonatal overnutrition accelerates the development of insulin resistance and exacerbates HFD-induced metabolic defects, possibly by worsening HFD-induced inflammatory response and impaired lipid metabolism.
authors: Laboratory of Lipid and Glucose Metabolism, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, People's Republic of China Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science Technology and Research (A*STAR), #02-02 Helios, 11 Biopolis Way, Singapore 138667, Singapore Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, Oregon 97006, USA Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119275, Singapore.
authors: Zhiguo
authors: Z
authors: Liu
authors: Chun Yan
authors: CY
authors: Lim
authors: Michelle Yu-Fah
authors: MY
authors: Su
authors: Stephanie Li Ying
authors: SL
authors: Soh
authors: Guanghou
authors: G
authors: Shui
authors: Markus R
authors: MR
authors: Wenk
authors: Kevin L
authors: KL
authors: Grove
authors: George K
authors: GK
authors: Radda
authors: Weiping
authors: W
authors: Han
authors: Xiaoqiu
authors: X
authors: Xiao
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology; D052439:Lipid Metabolism Disorders / Q000209:etiology / Q000378:metabolism; D008297:Male; D008659:Metabolic Diseases / Q000209:etiology* / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D044343:Overnutrition / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016207:Cytokines; D004041:Dietary Fats; D007328:Insulin
keywords: adipose tissue; fatty acids; glucose transport; insulin resistance; obesity