Catch-up growth following intra-uterine growth-restriction programmes an insulin-resistant phenotype in adipose tissue

Abstract

Background:It is now widely accepted that the early-life nutritional environment is important in determining susceptibility to metabolic diseases. In particular, intra-uterine growth restriction followed by accelerated postnatal growth is associated with an increased risk of obesity, type-2 diabetes and other features of the metabolic syndrome. The mechanisms underlying these observations are not fully understood.Aim:Using a well-established maternal protein-restriction rodent model, our aim was to determine if exposure to mismatched nutrition in early-life programmes adipose tissue structure and function, and expression of key components of the insulin-signalling pathway.Methods:Offspring of dams fed a low-protein (8%) diet during pregnancy were suckled by control (20%)-fed dams to drive catch-up growth. This ‘recuperated' group was compared with offspring of dams fed a 20% protein diet during pregnancy and lactation (control group). Epididymal adipose tissue from 22-day and 3-month-old control and recuperated male rats was studied using histological analysis. Expression and phosphorylation of insulin-signalling proteins and gene expression were assessed by western blotting and reverse-transcriptase PCR, respectively.Results:Recuperated offspring at both ages had larger adipocytes (P<0.001). Fasting serum glucose, insulin and leptin levels were comparable between groups but increased with age. Recuperated offspring had reduced expression of IRS-1 (P<0.01) and PI3K p110β (P<0.001) in adipose tissue. In adult recuperated rats, Akt phosphorylation (P<0.01) and protein levels of Akt-2 (P<0.01) were also reduced. Messenger RNA expression levels of these proteins were not different, indicating a post-transcriptional effect.Conclusion:Early-life nutrition programmes alterations in adipocyte cell size and impairs the protein expression of several insulin-signalling proteins through post-transcriptional mechanisms. These indices may represent early markers of insulin resistance and metabolic disease risk.

IUGR with infantile overnutrition programs an insulin-resistant phenotype through DNA methylation of peroxisome proliferator–activated receptor-γ coactivator-1α in rats

“…Numerous studies have concluded that IUGR individuals, especially those with postnatal accelerated growth, are prone to develop insulin resistance and T2DM in adulthood (11)(12)(13). Using a well-established rodent model, these experiments have found that CG-IUGR rats had higher methylation level of specific CpG sites of PGC-1α promoter, in contrast, reduced PGC-1α transcription activity, mitochondrial content as well as protein level of key components of insulin-signaling pathway in liver and muscle tissues.…”

“…Many intrauterine growth restriction (IUGR) infants experience postnatal accelerated growth (8), begetting shortterm (9) and long-term health benefits, especially in cognition and academic achievement (10). However, emerging evidence suggests that IUGR followed by postnatal accelerated growth (CG-IUGR) plays a role in the programing of adult metabolic disease risk (11)(12)(13), and the underlying molecular pathogenesis is unclear. Nevertheless, the epigenetic dysregulation has been implicated.…”

Maternal chromium restriction modulates miRNA profiles related to lipid metabolism disorder in mice offspring

“…Venu et al 28 reported that maternal Mg restriction increased pup body adipose percentage, and reduced lean body and fat-free mass at postnatal 90 days. Berends et al 29 found that pups from protein-restricted diet mothers had higher adipocytes at 22 days and 3 months. Maternal zinc deficiency increased body adipose ratio in offspring at six months of age.…”

Nutritional conditions in early life and risk of non-communicable diseases (NCDs) from the perspective of preemptive medicine in perinatal care

“…Since 'catch-up growth' has been reported to increase the risk of adult NCDs, 21,31,38,[69][70][71][72][73][74][75][76] nutritional interventions for nursing women and/or neonates may be another target for early interventions (Figure 8). However, Houk et al 102) demonstrated that children born small for gestational age without 'catch-up growth' were at high risk of short stature in adulthood and should be referred for growth hormone treatment.…”