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Long-term effect of early postnatal overnutrition on insulin resistance and serum fatty acid profiles in male rats.

Bei F, Jia J, Jia YQ, Sun JH, Liang F, Yu ZY, Cai W - Lipids Health Dis (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China. fionabei@163.com.

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.

No MeSH data available.


Related in: MedlinePlus

mRNA expression of key insulin signaling components in epididymal fat at 16 weeks. mRNA level of Irs-1, Akt2 and Glut4 were assessed by quantitative PCR in the epididymal fat of rats from normal litter (NL, open bar) and small litter (SL, closed bar). Results are expressed as mean ± S.E.M (n = 6, 4 litters from each group). *P < 0.05
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Fig6: mRNA expression of key insulin signaling components in epididymal fat at 16 weeks. mRNA level of Irs-1, Akt2 and Glut4 were assessed by quantitative PCR in the epididymal fat of rats from normal litter (NL, open bar) and small litter (SL, closed bar). Results are expressed as mean ± S.E.M (n = 6, 4 litters from each group). *P < 0.05

Mentions: In order to evaluate whether the changes in protein content are associated with changes in the levels of mRNA, quantitative real-time PCR was performed on mRNA isolated from adult SL and NL rats. At 16 weeks of age, early postnatal overnutrition resulted in a significant decrease in mRNA levels of Irs-1 and Glut4 (P < 0.05) in epididymal fat, paralleling the results of protein measurement (Fig. 6). In muscle a significant decrease in Glut4 mRNA (P < 0.05) was observed (Fig. 7), consistent with the western blot data, in addition to a marked reduction in Akt2 mRNA expression (P < 0.05, Fig. 7) which did not reflect a significant change at the protein level. In contrast, the protein level of Akt2 in epididymal fat was significantly lower in SL rats compared to NL rats, unlike the mRNA expression levels (P > 0.05) (Fig. 6). In line with the protein comparison, there is no significant difference in Irs-1 mRNA expression between two groups in skeletal muscle (Fig. 7).Fig. 6


Long-term effect of early postnatal overnutrition on insulin resistance and serum fatty acid profiles in male rats.

Bei F, Jia J, Jia YQ, Sun JH, Liang F, Yu ZY, Cai W - Lipids Health Dis (2015)

mRNA expression of key insulin signaling components in epididymal fat at 16 weeks. mRNA level of Irs-1, Akt2 and Glut4 were assessed by quantitative PCR in the epididymal fat of rats from normal litter (NL, open bar) and small litter (SL, closed bar). Results are expressed as mean ± S.E.M (n = 6, 4 litters from each group). *P < 0.05
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4549095&req=5

Fig6: mRNA expression of key insulin signaling components in epididymal fat at 16 weeks. mRNA level of Irs-1, Akt2 and Glut4 were assessed by quantitative PCR in the epididymal fat of rats from normal litter (NL, open bar) and small litter (SL, closed bar). Results are expressed as mean ± S.E.M (n = 6, 4 litters from each group). *P < 0.05
Mentions: In order to evaluate whether the changes in protein content are associated with changes in the levels of mRNA, quantitative real-time PCR was performed on mRNA isolated from adult SL and NL rats. At 16 weeks of age, early postnatal overnutrition resulted in a significant decrease in mRNA levels of Irs-1 and Glut4 (P < 0.05) in epididymal fat, paralleling the results of protein measurement (Fig. 6). In muscle a significant decrease in Glut4 mRNA (P < 0.05) was observed (Fig. 7), consistent with the western blot data, in addition to a marked reduction in Akt2 mRNA expression (P < 0.05, Fig. 7) which did not reflect a significant change at the protein level. In contrast, the protein level of Akt2 in epididymal fat was significantly lower in SL rats compared to NL rats, unlike the mRNA expression levels (P > 0.05) (Fig. 6). In line with the protein comparison, there is no significant difference in Irs-1 mRNA expression between two groups in skeletal muscle (Fig. 7).Fig. 6

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China. fionabei@163.com.

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.

No MeSH data available.


Related in: MedlinePlus