PCOS patients were frequently characterized by lower plasma vitamin D levels. The mechanisms involved in this dysfunction remains still debated, therefore we evaluated the role of androgen, insulin and body weight on the serum VitD levels in women with or without PCOS. Eighty one patients 18-42 yrs old were studied into "SUMMER" and "WINTER" seasonal period: thirty seven PCOS, seventeen no-ovarian hyperandrogenic (noPCOS), twelve functional hypothalamic amenorrhea (FHA) and finally fifteen healthy (Con). Patients were further divided into: lean (L), obese (O), normo- (nINS) and hyperinsulinemic (hINS). All hormonal and metabolic parameters were measured at 1-7 days of the menstrual cycle. Our results show that VitD levels were lower in PCOS and in noPCOS than in FHA and Con, in particular in (O) and (hINS) PCOSs. Both in summer and in winter, PCOSs had basal VitD levels significantly lower than FHA and Con, whereas they were similar to noPCOS. Yet, LhINS and OPCOS had VitD levels lower than Con and noPCOS. VitD levels were comparable in LnINS PCOS and Con. In conclusion, PCOSs had levels of VitD lower than controls. Weight and hyperinsulinemia had a significant influence on these values. Finally, over 70% of our healthy patients had VitD deficiency.
Insulin resistance and obesity are associated with a reduction of mitochondrial content in various tissues of mammals. Moreover, a reduced nitric oxide (NO) bioavailability impairs several cellular functions, including mitochondrial biogenesis and insulin-stimulated glucose uptake, two important mechanisms of body adaptation in response to physical exercise. Although these mechanisms have been thoroughly investigated in skeletal muscle and heart, few studies have focused on the effects of exercise on mitochondria and glucose metabolism in adipose tissue. In this study, we compared the in vivo effects of chronic exercise in subcutaneous adipose tissue of wild-type (WT) and endothelial NO synthase (eNOS) knockout (eNOS(-/-)) mice after a swim training period. We then investigated the in vitro effects of NO on mouse 3T3-L1 and human subcutaneous adipose tissue-derived adipocytes after a chronic treatment with an NO donor: diethylenetriamine-NO (DETA-NO). We observed that swim training increases mitochondrial biogenesis, mitochondrial DNA content, and glucose uptake in subcutaneous adipose tissue of WT but not eNOS(-/-) mice. Furthermore, we observed that DETA-NO promotes mitochondrial biogenesis and elongation, glucose uptake, and GLUT4 translocation in cultured murine and human adipocytes. These results point to the crucial role of the eNOS-derived NO in the metabolic adaptation of subcutaneous adipose tissue to exercise training.
Endurance exercise training increases cardiac energy metabolism through poorly understood mechanisms. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) in cardiomyocytes contributes to cardiac adaptation. Here we demonstrate that the NO donor diethylenetriamine-NO (DETA-NO) activated mitochondrial biogenesis and function, as assessed by upregulated peroxisome proliferator-activated receptor-? coactivator-1? (PGC-1?), nuclear respiratory factor 1, and mitochondrial transcription factor A (Tfam) expression, and by increased mitochondrial DNA content and citrate synthase activity in primary mouse cardiomyocytes. DETA-NO also induced mitochondrial biogenesis and function and enhanced both basal and insulin-stimulated glucose uptake in HL-1 cardiomyocytes. The DETA-NO-mediated effects were suppressed by either PGC-1? or Tfam small-interference RNA in HL-1 cardiomyocytes. Wild-type and eNOS(-/-) mice were subjected to 6 wk graduated swim training. We found that eNOS expression, mitochondrial biogenesis, mitochondrial volume density and number, and both basal and insulin-stimulated glucose uptake were increased in left ventricles of swim-trained wild-type mice. On the contrary, the genetic deletion of eNOS prevented all these adaptive phenomena. Our findings demonstrate that exercise training promotes eNOS-dependent mitochondrial biogenesis in heart, which behaves as an essential step in cardiac glucose transport.
Mammals possess two types of adipose tissue, white (WAT) and brown (BAT). The uncoupling protein 1 (UCP1) is a hallmark of BAT, being the pivotal player for cold-induced thermogenesis. WAT can acquire BAT characteristics with up-regulation of UCP1 after cold exposure or adrenergic stimulation. In the present study we demonstrated that human white adipocytes express the cold-sensing receptor TRPM8 which activation by menthol and icilin induced a rise in [Ca(2+)]i and UCP1 expression, increased mitochondrial membrane potential, glucose uptake and heat production. The induction of "brown-like" phenotype in human white adipocytes after TRPM8 activation was supported by ultrastructural morphological changes of mitochondrial morphology and of their intracellular localization, with no modifications of the genes regulating mitochondrial biogenesis. In conclusion human white adipocytes express the cold receptor TRPM8 which activation induces their "browning" supporting a possible role of this receptor in the control of adipose tissue metabolism and body energy balance.
The expression of insulin receptor (IR), together with that of glucose transporters 1 and 4 (GLUT1-4) and of Insulin Growth Factor-I and -II (IGF-I,-II) in the endometrium of healthy and young women in both phases of menstrual cycle was assessed. Sixteen out of 20 healthy and normal menstruating volunteers were studied. Endometrial samplings were performed in every subject, twice in the same cycle, during the follicular and luteal phase respectively. The mRNA expression of IR, GLUT1-4, IGF-I and -II were evaluated by real-time quantitative RT-PCR and immunostaining reactions. Our results indicate that IR, GLUT1-4, IGF-I and -II mRNAs were expressed in both phases of the endometrial cycle: GLUT4 and IGF-I mRNA expression were significantly higher in the follicular phase and localized at the epithelial and stromal cell level, respectively, whereas IR, GLUT1 and IGF-II mRNA expression were mostly present in the secretory phase and mainly localized at the stromal level. An inverse tendency of IR and GLUT4 mRNA expression was respectively observed from follicular to luteal phase. In conclusion our data suggest that IR, glucose transporters and IGFs are significantly and differently expressed at the endometrial level throughout the menstrual cycle and that human endometrium cyclically undergoes through a transitory condition from normal to an insulin-resistance state.
The low-grade chronic inflammation present in obesity has been recognized as a risk factor for thrombosis, atherosclerosis and cardiovascular complications. In this context, production by adipose organ of a number of inflammatory adipokines could play a crucial role. It has been reported that obesity represents a risk factor for acquired thrombotic thrombocytopenic purpura (TTP), a disease caused by ADAMTS13 deficiency because of anti-ADAMTS13 antibodies, but the pathophysiological link between obesity and TTP is still unknown. We aimed to investigate mechanisms linking obesity to risk of TTP.
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