Abstract
BackgroundIncreasing 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.MethodsRats 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.ResultsSL 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.ConclusionsThis 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.
Highlights
The dramatic increase in the prevalence of obesity in recent years is a global health problem because it significantly increases the risk of adult-onset metabolic diseases such as glucose intolerance, insulin resistance (IR), Type 2 diabetes and cardiovascular disorders
Organ weights and metabolic parameters in the Normal litter (NL) and Small litter (SL) groups To further characterize the effects of early postnatal overnutrition in adulthood, rats were killed at 16 weeks and their livers, hindlimb gastrocnemius muscles, epididymal fat pads and perirenal fat pads were harvested and weighed
We focused on the consequences of overnutrition during early postnatal life on serum fatty acid profiles and alterations of insulin signaling cascades in skeletal muscle and visceral white adipose tissue in order to determine whether early nutritional experience may influence the levels of key components of the insulin signaling pathway which play an important role in IR
Summary
The dramatic increase in the prevalence of obesity in recent years is a global health problem because it significantly increases the risk of adult-onset metabolic diseases such as glucose intolerance, insulin resistance (IR), Type 2 diabetes and cardiovascular disorders. In addition to causing the excessive energy intake in developed countries, it has been recognized that nutrient availability during early postnatal life has an important influence on obesity, IR and resulting adult health [3,4,5]. 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. We investigated the impact of overnutrition during the suckling period on body weight, serum biochemistry and serum fatty acid metabolomics in male rats
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