Muscle glycogen stores were maintained after a 5-wk high-fat diet period whereas IMCL content was more than doubled. Endurance performance capacity was maintained at moderate to high-exercise intensities with a significantly larger contribution of lipids to total energy turnover.
Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). While SPY has been shown to suppress gibberellin signaling and to promote cytokinin (CK) responses, its catalytic OGT activity was never demonstrated and its effect on protein fate is not known. We previously showed that SPY interacts physically and functionally with TCP14 and TCP15 to promote CK responses. Here, we aimed to identify how SPY regulates TCP14/15 activities and how these TCPs promote CK responses. We show that SPY activity is required for TCP14 stability. Mutation in the putative OGT domain of SPY (spy-3) stimulated TCP14 proteolysis by the 26S proteasome, which was reversed by mutation in CULLIN1 (CUL1), suggesting a role for SKP, CUL1, F-box E3 ubiquitin ligase in TCP14 proteolysis. TCP14 proteolysis in spy-3 suppressed all TCP14 misexpression phenotypes, including the enhanced CK responses. The increased CK activity in TCP14/ 15-overexpressing flowers resulted from increased sensitivity to the hormone and not from higher CK levels. TCP15 overexpression enhanced the response of the CK-induced synthetic promoter pTCS to CK, suggesting that TCP14/15 affect early steps in CK signaling. We propose that posttranslational modification of TCP14/15 by SPY inhibits their proteolysis and that the accumulated proteins promote the activity of the CK phosphorelay cascade in developing Arabidopsis leaves and flowers.O-linked GlcNAc (O-GlcNAc) modification of Ser and Thr residues by the nucleocytoplasmic O-GlcNAc transferases (OGTs) regulates the posttranslational fate and function of target proteins (Hart et al., 2007;Butkinaree et al., 2010). In mammalian cells, O-GlcNAcylation affects protein localization, phosphorylation, and stability and plays a role in signal transduction, transcription, and proteasomal degradation (Roos and Hanover,
ObjectivesWe compared androgen and gonadotropin values in HIV-infected men who did and did not develop lipoatrophy on combination antiretroviral therapy (cART). MethodsFrom a population of 136 treatment-naïve male Caucasians under successful zidovudine/ lamivudine-based cART, the 10 patients developing lipoatrophy (cases) were compared with 87 randomly chosen controls. Plasma levels of free testosterone (fT), dehydroepiandrosterone (DHEA), follicle-stimulating hormone and luteinizing hormone (LH) were measured at baseline and after 2 years of cART. ResultsAt baseline, 60% of the cases and 71% of the controls showed abnormally low fT values. LH levels were normal or low in 67 and 94% of the patients, respectively, indicating a disturbance of the hypothalamic-pituitary-gonadal axis. fT levels did not significantly change after 2 years of cART. Cases showed a significant increase in LH levels, while controls showed a significant increase in DHEA levels. In a multivariate logistic regression model, lipoatrophy was associated with higher baseline DHEA levels (P 5 0.04), an increase in LH levels during cART (P 5 0.001), a lower body mass index and greater age. ConclusionsHypogonadism is present in the majority of HIV-infected patients. The development of cART-related lipoatrophy is associated with an increase in LH and a lack of increase in DHEA levels. 427The lipodystrophy syndrome represents a well-known adverse effect of cART consisting of fat redistribution abnormalities, insulin resistance and dyslipidaemia [4,5]. Lipodystrophy includes central lipohypertrophy and peripheral lipoatrophy. The latter has been associated with the toxic effects of nucleoside reverse transcriptase inhibitors (NRTIs) on mitochondria [6][7][8] and cART-related dysregulation of the expression of cytokines and cytokine receptors, and there are some reports of genetic predispositions, based on single nucleotide polymorphisms, to cART-related lipoatrophy [6,[9][10][11][12]. We showed in a previous study that there is no association between changes in leptin levels and the development of lipoatrophy [13]. In this study, we evaluated the association between sex hormone levels and the development of lipoatrophy in HIV-infected men treated with cART. Materials and methodsThe Swiss HIV Cohort Study (SHCS; www.shcs.ch) prospectively follows HIV-infected adults. Every 6 months, clinical data are collected and blood plasma samples are drawn, analysed and stored at À 80 1C for future research. Study designWe performed a nested case-control study in HIV-infected, antiretroviral therapy-naïve Caucasian men who were successfully treated with zidovudine (ZDV)-and lamivudine (3TC)-based cART for a minimum of 2 years. Patients with acute opportunistic infections, uncontrolled AIDSdefining illnesses, diabetes mellitus, androgen treatment or a change in cART during the study period were excluded. Cases developing lipoatrophy and negative controls were identified and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), free testoste...
Objectives To assess the prevalence of abnormal testosterone and gonadotropin values in HIV-infected men before and after 2 years of combination antiretroviral therapy (cART). Design Multicentre cohort of HIV-infected adults. Methods We identified 139 Caucasian antiretroviral-naive male patients who started zidovudine/ lamivudine-based cART that was virologically successful over a 2 year period. Ninety-seven were randomly chosen and plasma hormone determinations of free testosterone (fT) and luteinizing hormone (LH) at baseline and after 2 years of cART were evaluated. Results At baseline 68 patients (70%) had subnormal fT levels. In these, LH levels were low in 44%, normal in 47% and high in 9%. There was a trend for an association between lower CD4+ T-cell counts and hypogonadism. Most participants had normal FSH levels. No significant changes of fT, LH and FSH levels were observed after 2 years of cART. Conclusions Low fT levels, mainly with normal or low LH levels and thus indicating secondary hypogonadism, are found in the majority of HIV-infected men and do not resolve during 2 years of successful cART.
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