Altered liver expression of genes involved in lipid and glucose metabolism in mice with partial IGF-1 deficiency: an experimental approach to metabolic syndrome

Abstract

BackgroundInsulin growth factor 1 (IGF-1) has multiple effects on metabolism. Much evidence suggests that the deficiency of this hormone increases insulin resistance, impairs lipid metabolism, augments oxidative damage and deregulates the neuro-hormonal axis. An inverse relationship between IGF-1 levels and the prevalence of Metabolic Syndrome (MetS) with its cardiovascular complications has been identified. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. In order to elucidate such mechanisms, the aim of this work was to study, in mice with partial IGF-1 deficiency, liver expression of genes involved in glucose and lipid metabolism as well as serum levels of glucose, triglycerides and cholesterol, as well as liver malondialdehyde (MDA) levels, as a marker for oxidative damage.MethodsThree experimental groups were studied in parallel: Controls (CO), wild type mice (igf-1+/+); untreated heterozygous mice (Hz, igf-1+/−) and Hz (igf-1+/−) mice treated with low doses of IGF-1 for 10 days (Hz + IGF-1).ResultsA reduction of IGF-1 serum levels in the Hz group was found, which was normalized by IGF-1 therapy. Serum levels of glucose, triglycerides and cholesterol were significantly increased in the untreated Hz group as compared to both controls and Hz + IGF-1 groups. The expression of genes involved in gluconeogenesis, glycogenolysis, lipid synthesis and transport, and catabolism were altered in untreated Hz animals and the expression of most of them was normalized by IGF-1 therapy; MDA was also significantly increased in the Hz untreated group.ConclusionsThe mere partial IGF-1 deficiency is responsible for the reduction in the expression of genes involved in glucose and lipid metabolism, resulting in dyslipidemia and hyperglycemia. Such genetic alterations may seriously contribute to the establishment of MetS.

Genetic risk variants for metabolic traits in Arab populations

“…Involvement of some of the identified gene loci (namely Chr15:40531386/ ZNF106 , Chr12:101494770/[ IGF1,PAH ], rs883431/ SLC28A3 , rs925530/ TMEM120B , and rs17716285/ KSR1 ) in processes relating to metabolic traits have been previously demonstrated in mice or cell lines1828495051 (see Table 5). Therefore, our study gives suggestive evidence for involvement of these gene loci in human too.…”

“…It plays an important role in cell growth and anabolism function. Recent study on IGF1 deficient mice showed elevated levels of triglyceride28; and another study on IGF1 treatment in healthy individuals showed reduced levels of fasting and postprandial triglyceride29. IGF1 deficiency has been reported to be involved in the development of diabetic retinopathy in Thalassemia major patients from Italy30 and in the development of metabolic syndrome in a British cohort31.…”

IGF-1 modulates gene expression of proteins involved in inflammation, cytoskeleton, and liver architecture

“…The preference for IGF-1 treatment at low doses was chosen following the experience acquired from previous studies belonging to the same model [4–6, 8, 9, 11, 13, 14, 18, 21, 24, 35, 39, 40, 45]. Briefly, such dosage is enough to restore normal circulating IGF-1 values without inducing hypoglycemia and any adverse effects.…”

Disparate Central and Peripheral Effects of Circulating IGF-1 Deficiency on Tissue Mitochondrial Function

“…IGF-1 stimulates preadipocyte differentiation but has a limited effect on mature adipocytes [56]. However, partial IGF-1 deficiency decreases expression of genes involved in lipid metabolism [57]. To determine the effect of reduced circulating IGF-1 on lipid metabolism, we measured both subcutaneous fat mass and epididymal fat mass and mitochondrial function.…”