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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

Protein expression of key insulin signaling components in epididymal fat at 16 weeks. Protein levels of insulin receptor substrate-1 (Irs-1), protein kinase B (Akt2) and glucose transporter 4 (Glut4) in the epididymal fat of rats from normal litters (NL) and small litters (SL) were assessed by western blotting. Representative blots are shown in (a). Relative protein levels were quantified by scanning densitometry of the bands (b). Results are expressed as mean ± S.E.M (n = 6, 4 litters from each group). **P < 0.01, ***P < 0.001
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Fig4: Protein expression of key insulin signaling components in epididymal fat at 16 weeks. Protein levels of insulin receptor substrate-1 (Irs-1), protein kinase B (Akt2) and glucose transporter 4 (Glut4) in the epididymal fat of rats from normal litters (NL) and small litters (SL) were assessed by western blotting. Representative blots are shown in (a). Relative protein levels were quantified by scanning densitometry of the bands (b). Results are expressed as mean ± S.E.M (n = 6, 4 litters from each group). **P < 0.01, ***P < 0.001

Mentions: Insulin resistance may arise from downregulation of key components of the insulin signaling pathway. To investigate whether this was the case following postnatal overnutrition, the levels of three such proteins, Irs-1, Akt2 and Glut4, were measured by western blotting in lysates from epididymal fat and gastrocnemius muscle isolated from SL and NL rats at 16 weeks of age. A significant decrease in expression of all of the above proteins was observed in the epididymal fat of SL rats compared to NL controls (P < 0.05) (Fig. 4). In skeletal muscle, the protein content of Glut4 was found to be significantly decreased in SL rats compared to NL, but no significant differences were observed in the protein levels of Irs-1 and Akt2 between the two groups (Fig. 5).Fig. 4


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)

Protein expression of key insulin signaling components in epididymal fat at 16 weeks. Protein levels of insulin receptor substrate-1 (Irs-1), protein kinase B (Akt2) and glucose transporter 4 (Glut4) in the epididymal fat of rats from normal litters (NL) and small litters (SL) were assessed by western blotting. Representative blots are shown in (a). Relative protein levels were quantified by scanning densitometry of the bands (b). Results are expressed as mean ± S.E.M (n = 6, 4 litters from each group). **P < 0.01, ***P < 0.001
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4549095&req=5

Fig4: Protein expression of key insulin signaling components in epididymal fat at 16 weeks. Protein levels of insulin receptor substrate-1 (Irs-1), protein kinase B (Akt2) and glucose transporter 4 (Glut4) in the epididymal fat of rats from normal litters (NL) and small litters (SL) were assessed by western blotting. Representative blots are shown in (a). Relative protein levels were quantified by scanning densitometry of the bands (b). Results are expressed as mean ± S.E.M (n = 6, 4 litters from each group). **P < 0.01, ***P < 0.001
Mentions: Insulin resistance may arise from downregulation of key components of the insulin signaling pathway. To investigate whether this was the case following postnatal overnutrition, the levels of three such proteins, Irs-1, Akt2 and Glut4, were measured by western blotting in lysates from epididymal fat and gastrocnemius muscle isolated from SL and NL rats at 16 weeks of age. A significant decrease in expression of all of the above proteins was observed in the epididymal fat of SL rats compared to NL controls (P < 0.05) (Fig. 4). In skeletal muscle, the protein content of Glut4 was found to be significantly decreased in SL rats compared to NL, but no significant differences were observed in the protein levels of Irs-1 and Akt2 between the two groups (Fig. 5).Fig. 4

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