ABSTRACT
BACKGROUND: Increasing evidence suggests that overnutrition during the early postnatal period, a critical window of development, increases the risk of adult-onset obesity and insulin resistance. In this study, we investigated the impact of overnutrition during the suckling period on body weight, serum biochemistry and serum fatty acid metabolomics in male rats. METHODS: Rats raised in small litters (SL, 3 pups/dam) and normal litters (NL, 10 pups/dam) were used to model early postnatal overnutrition and control, respectively. Serum glucose, triglyceride, high-density lipoprotein-cholesterol, free fatty acid, insulin and leptin concentrations were assayed using standard biochemical techniques. Serum fatty acids were identified and quantified using a gas chromatography-mass spectrometry-based metabolomic approach. mRNA and protein levels of key components of the insulin receptor signaling pathway were measured in epididymal fat and gastrocnemius muscle by quantitative PCR and western blotting. RESULTS: SL rats were 37.3 % and 15.1 % heavier than NL rats at weaning and 16-weeks-old, respectively. They had increased visceral fat mass, adult-onset insulin resistance and glucose intolerance as well as elevated serum levels of free fatty acids and triglycerides. All detectable fatty acids were elevated in the serum of SL pups at weaning compared to NL controls, and significant increases in the levels of four fatty acids (palmitic acid, palmitoleic acid, oleic acid and arachidonic acid) persisted into adulthood. Moreover, a significantly positive correlation was identified between an insulin resistance index (HOMA-IR) and concentrations of myristic, palmitic, palmitoleic and oleic acid in serum at postnatal 16 weeks. Early postnatal overnutrition also resulted in a significant downregulation of insulin receptor substrate-1 (Irs-1), protein kinase B (Akt2) and glucose transporter 4 (Glut4) at the protein level in epididymal fat of SL rats at 16 weeks, accompanied by decreased mRNA levels for Irs-1 and Glut4. In gastrocnemius muscle, Akt2 and Glut4 mRNA and Glut4 protein levels were significantly decreased in SL rats. CONCLUSIONS: This study demonstrates that early postnatal overnutrition can have long-lasting effects on body weight and serum fatty acid profiles and can lead to impaired insulin signaling pathway in visceral white adipose tissue and skeletal muscle, which may play a major role in IR.
Subject(s)
Fatty Acids, Nonesterified/blood , Insulin Resistance , Obesity/genetics , Overnutrition/genetics , RNA, Messenger/blood , Adipose Tissue, White/metabolism , Animals , Blood Glucose/metabolism , Gene Expression Regulation , Glucose Transporter Type 4/blood , Glucose Transporter Type 4/genetics , Humans , Insulin/blood , Insulin/genetics , Insulin Receptor Substrate Proteins/blood , Insulin Receptor Substrate Proteins/genetics , Leptin/blood , Leptin/genetics , Lipoproteins, HDL/blood , Litter Size , Male , Obesity/blood , Overnutrition/blood , Proto-Oncogene Proteins c-akt/blood , Proto-Oncogene Proteins c-akt/genetics , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , Signal Transduction , Triglycerides/bloodABSTRACT
OBJECTIVE: To observe the effect of recipes replenishing qi and activating blood on cell proliferation and apoptosis in the liver of natural aging rats. METHODS: Natural aging rats were under administration of recipes replenishing qi or activating blood for 4 months. The liver of the rats was prepared into cell suspension for determination of cell proliferation and apoptosis with PI-staining and flow cytometer. RESULTS: (1) Compared with those of the young rats, the cells in G(0)-G1 phase in the liver tissue of aging rats were increased (P< 0.01), and apoptosis cells were increased (P< 0.01), while the cells in S and G2-M phases were decreased (P< 0.01). (2) Compared with those of the aging rats, the cells in G(0)-G1 phase in the liver tissue of aging rats administered recipes replenishing qi or activating blood were decreased (P< 0.01), and it was more obvious in activating blood group than in replenishing qi group (P< 0.01); the cells in S and G2-M phases were increased (P< 0.01) and there was no significant difference between the activating blood group and the replenishing qi group (P> 0.05). (3) The apoptosis cells in replenishing qi or activating blood group were decreased significantly (P< 0.01), and the effect of replenishing qi was better than that of activating blood (P< 0.01). CONCLUSION: (1) Cell proliferation is decreased and apoptosis is increased in the liver tissue of natural aging rats. (2) Recipes replenishing qi or activating blood can accelerate cell proliferation in the liver tissue of natural aging rats, and the effect of activating blood was slightly stronger than that of replenishing qi. (3) Recipes replenishing qi or activating blood can inhibit cell apoptosis in the liver tissue of natural aging rats, and the effect of replenishing qi was better than that of activating blood.