Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150μM or 400μM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when evaluated in an in vitro model of DN. Altogether, our findings suggest that DFX preconditioning of AD-MSCs improves their therapeutic potential and should be considered as a potential strategy for the generation of new alternatives for DN treatment.
Introduction: Ballet dancers (BDs) have a negative energy balance related to physical training that results in alterations in body composition, sexual development, and adipokine secretion. Our aims were to study anthropometric parameters, body composition, and their relationship with adipokines throughout pubertal development. Subjects and methods: We carried out a prospective follow-up study of 22 female Caucasian BDs (Tanner II stage) followed throughout puberty. Nutritional status was determined by measurement of height, weight, and body mass index (BMI). We calculated growth velocity, bone maturity, and body composition at Tanner stages II, III, and V by dual energy X-ray absorptiometry. Circulating leptin, adiponectin, and soluble leptin receptor (sObR) levels were determined. Results: BDs presented a delay in skeletal maturation during puberty, without affectation of final height. Energy intake was deficient according to their physical exercise, and they had a delay of 1 year in the mean age of menarche. Leptin levels were decreased, whereas sObR and adiponectin levels were increased throughout puberty. The percentage of trunk fat, total fat mass, and fat of the extremities was decreased throughout the study period (P!0.01). Lean mass was increased in the lower extremities, and bone mineral density was normal. Conclusion: A negative energy balance together with maintained physical exercise induced modifications in body composition in BDs. Changes in leptin and adiponectin levels appear to be more related to total fat content than to BMI. Furthermore, the onset and delayed progress of puberty may be related with an inadequate energy balance due to increased exercise.
Background: Modifications in body fat in obese patients during puberty determine changes in adipokines that affect insulin sensitivity. Aims: We hypothesized that the leptin/adiponectin (L/A) ratio and free leptin index (FLI) are good markers of insulin resistance (IR) and total body fat (TBF) during pubertal development. Methods: A prospective study of 32 obese girls (OG) and age-matched control girls (CG) was performed. OG were divided into those that maintained a weight loss (WL) of >1 SD of initial body mass index (BMI) (WL group, n = 25) and those without WL (NWL group, n = 7). Oral glucose tolerance tests (OGTT) were performed to evaluate IR. Correlations of adipokines, L/A, and FLI with BMI, waist circumference, percentage of TBF (%TBF) and IR were performed over pubertal development. Results: The L/A ratio and FLI were increased in OG at baseline. Both indexes decreased in the WL group as puberty progressed, with no change in CG or NWL. In the WL group, a correlation between L/A and FLI with OGTT and %TBF, and L/A and homeostasis model assessment (HOMA) was found throughout the study. Conclusion: The L/A ratio and FLI are good markers to follow changes in IR and %TBF after WL during puberty. Insulin more accurately reflects the changes in IR than HOMA.
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