Consistent evidence associates IGF-1 deficiency and metabolic syndrome. In this review, we will focus on the metabolic effects of IGF-1, the concept of metabolic syndrome and its clinical manifestations (impaired lipid profile, insulin resistance, increased glucose levels, obesity, and cardiovascular disease), discussing whether IGF-1 replacement therapy could be a beneficial strategy for these patients. The search plan was made in Medline for Pubmed with the following mesh terms: IGF-1 and “metabolism, carbohydrate, lipids, proteins, amino acids, metabolic syndrome, cardiovascular disease, diabetes” between the years 1963–2015. The search includes animal and human protocols. In this review we discuss the relevant actions of IGF-1 on metabolism and the implication of IGF-1 deficiency in the establishment of metabolic syndrome. Multiple studies (in vitro and in vivo) demonstrate the association between IGF-1 deficit and deregulated lipid metabolism, cardiovascular disease, diabetes, and an altered metabolic profile of diabetic patients. Based on the available data we propose IGF-1 as a key hormone in the pathophysiology of metabolic syndrome; due to its implications in the metabolism of carbohydrates and lipids. Previous data demonstrates how IGF-1 can be an effective option in the treatment of this worldwide increasing condition. It has to distinguished that the replacement therapy should be only undertaken to restore the physiological levels, never to exceed physiological ranges.

Rationale: Resolution mechanisms are central in both the maintenance of homeostasis and the return to catabasis following tissue injury and/or infections. Amongst the pro-resolving mediators, the essential fatty acid-derived specialized pro-resolving lipid mediators (SPM) govern immune responses to limit disease severity. Notably, little is known about the relationship between the expression and activity of SPM pathways, circulating phagocyte function and disease severity in patients infected with novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leading to coronavirus disease 2019 (COVID-19). Objective: Herein, we investigated the link between circulating SPM concentrations and phagocyte activation status and function in COVID-19 patients (n=39) compared to healthy (n=12) and post-COVID-19 (n=8) volunteers. Methods and Results: Lipid mediator profiling demonstrated that plasma SPM concentrations were upregulated in patients with mild COVID-19 and are downregulated in those with severe disease. SPM concentrations were correlated with both circulating phagocyte activation status and function. Perturbations in plasma SPM concentrations and phagocyte activation were retained after the resolution of COVID-19 clinical symptoms. Treatment of patients with dexamethasone upregulated both the expression of SPM biosynthetic enzymes in circulating phagocytes and plasma concentration of these mediators. Furthermore, incubation of phagocytes from COVID-19 patients with SPM rectified their phenotype and function. This included a downregulation in the expression of activation markers, a decrease in the Tissue Factor and inflammatory cytokine expression, and an upregulation of bacterial phagocytosis. Conclusions: The present findings suggest that downregulation of systemic SPM concentrations is linked with both increased disease severity and dysregulated phagocyte function. They also identify the upregulation of these mediators by dexamethasone as a potential mechanism in host protective activities elicited by this drug in COVID-19 patients. Taken together, our findings elucidate a role for altered resolution mechanisms in the disruption of phagocyte responses and the propagation of systemic inflammation in COVID-19.

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.

Parkinson's disease (PD) is a neurodegenerative disorder that results in the death of dopaminergic neurons within the substantia nigra pars compacta and the reduction in dopaminergic control over striatal output neurons, leading to a movement disorder most commonly characterized by akinesia or bradykinesia, rigidity and tremor. Also, PD is less frequently depicted by sensory symptoms (pain and tingling), hyposmia, sleep alterations, depression and anxiety, and abnormal executive and working memory related functions. On the other hand, insulin-like growth factor 1 (IGF-1) is an endocrine, paracrine and autocrine hormone with several functions including tissue growth and development, insulin-like activity, proliferation, pro-survival, anti-aging, antioxidant and neuroprotection, among others. Herein this review tries to summarize all experimental and clinical data to understand the pathophysiology and development of PD, as well as its clear association with IGF-1, supported by several lines of evidence: (1) IGF-1 decreases with age, while aging is the major risk for PD establishment and development; (2) numerous basic and translational data have appointed direct protective and homeostasis IGF-1 roles in all brain cells; (3) estrogens seem to confer women strong protection to PD via IGF-1; and (4) clinical correlations in PD cohorts have confirmed elevated IGF-1 levels at the onset of the disease, suggesting an ongoing compensatory or "fight-to-injury" mechanism.

Even though the liver synthesizes most of circulating IGF-1, it lacks its receptor under physiological conditions. However, according to previous studies, a damaged liver expresses the receptor. For this reason, herein, we examine hepatic histology and expression of genes encoding proteins of the cytoskeleton, extracellular matrix, and cell-cell molecules and inflammation-related proteins. A partial IGF-1 deficiency murine model was used to investigate IGF-1’s effects on liver by comparing wild-type controls, heterozygous igf1+/−, and heterozygous mice treated with IGF-1 for 10 days. Histology, microarray for mRNA gene expression, RT-qPCR, and lipid peroxidation were assessed. Microarray analyses revealed significant underexpression of igf1 in heterozygous mice compared to control mice, restoring normal liver expression after treatment, which then normalized its circulating levels. IGF-1 receptor mRNA was overexpressed in Hz mice liver, while treated mice displayed a similar expression to that of the controls. Heterozygous mice showed overexpression of several genes encoding proteins related to inflammatory and acute-phase proteins and underexpression or overexpression of genes which coded for extracellular matrix, cytoskeleton, and cell junction components. Histology revealed an altered hepatic architecture. In addition, liver oxidative damage was found increased in the heterozygous group. The mere IGF-1 partial deficiency is associated with relevant alterations of the hepatic architecture and expression of genes involved in cytoskeleton, hepatocyte polarity, cell junctions, and extracellular matrix proteins. Moreover, it induces hepatic expression of the IGF-1 receptor and elevated acute-phase and inflammation mediators, which all resulted in liver oxidative damage.Electronic supplementary materialThe online version of this article (doi:10.1007/s13105-016-0545-x) contains supplementary material, which is available to authorized users.