Abstract | BACKGROUND: METHODS: Rats raised in small litters (SLs, three pups/dam, n = 10) and normal litters (NLs, 10 pups/dam, n = 10) were used to model early postnatal overfeeding and act as controls, respectively. miR-221 and proteins related to the phosphoinositide 3-kinases (PI3K)/ protein kinase B (AKT) pathway were assessed in the liver. RESULTS: Early postnatal overfeeding significantly increased body weight, visceral fat index, blood glucose, serum triglycerides, and the homeostasis model assessment of insulin resistance at 9 weeks. Real-time polymerase chain reaction (PCR) and western blot analysis revealed that postnatal overfeeding induced insulin receptor and insulin receptor substrate 2 expression, but decreased PI3K and AKT phosphorylation in the liver. Quantitative real-time PCR showed that hepatic miR-221 was significantly overexpressed in the SL group. CONCLUSIONS: These results indicate that postnatal overfeeding induces hepatic miR-221 overexpression and impairs the PI3K/AKT signal pathway, which may cause insulin resistance. IMPACT: We first report postnatal overfeeding induces hepatic miR-221 expression. Postnatal overfeeding impairs PI3K/AKT pathway in the liver of adult rats. Postnatal overfeeding induces obesity and high blood glucose. Avoidance of overfeeding during early postnatal life may prevent obesity and T2DM.
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Authors | Fang Huang, Pingping Zhu, Jingwen Wang, Jie Chen, Wenting Lin |
Journal | Pediatric research
(Pediatr Res)
Vol. 89
Issue 1
Pg. 143-149
(01 2021)
ISSN: 1530-0447 [Electronic] United States |
PMID | 32305038
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Insr protein, rat
- Insulin Receptor Substrate Proteins
- Irs2 protein, rat
- MIRN221 microRNA, rat
- MicroRNAs
- Phosphatidylinositol 3-Kinase
- Receptor, Insulin
- Proto-Oncogene Proteins c-akt
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Topics |
- Adiposity
- Animals
- Disease Models, Animal
- Hyperphagia
(enzymology, genetics, pathology)
- Insulin Receptor Substrate Proteins
(genetics, metabolism)
- Insulin Resistance
(genetics)
- Liver
(enzymology, pathology)
- Male
- MicroRNAs
(genetics, metabolism)
- Obesity
(enzymology, genetics, pathology)
- Phosphatidylinositol 3-Kinase
(genetics, metabolism)
- Phosphorylation
- Proto-Oncogene Proteins c-akt
(metabolism)
- Rats, Sprague-Dawley
- Receptor, Insulin
(genetics, metabolism)
- Signal Transduction
- Weight Gain
- Rats
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