BackgroundOxidative stress in adipocyte plays a central role in the pathogenesis of obesity as well as in the associated cardiovascular complications. The putative uremic toxin indoxyl sulfate induces oxidative stress and dramatically alters adipocyte phenotype in vitro. Mice that have undergone partial nephrectomy serve as an experimental model of uremic cardiomyopathy. This study examined the effects on adipocytes of administering a peptide that reduces oxidative stress to the mouse model.MethodsA lentivirus vector introduced the peptide NaKtide with an adiponectin promoter into the mouse model of experimental uremic cardiomyopathy, intraperitoneally. Then adipocyte-specific expression of the peptide was assessed for mice fed a standard diet compared with mice fed a western diet enriched in fat and fructose.ResultsPartial nephrectomy induced cardiomyopathy and anemia in the mice, introducing oxidant stress and an altered molecular phenotype of adipocytes that increased production of systemic inflammatory cytokines instead of accumulating lipids, within 4 weeks. Consumption of a western diet significantly worsened the adipocyte oxidant stress, but expression of NaKtide in adipocytes completely prevented the worsening. The peptide-carrying lentivirus achieved comparable expression in skeletal muscle, but did not ameliorate the disease phenotype.ConclusionsAdipocyte-specific expression of NaKtide, introduced with a lentiviral vector, significantly ameliorated adipocyte dysfunction and uremic cardiomyopathy in partially nephrectomized mice. These data suggest that the redox state of adipocytes controls the development of uremic cardiomyopathy in mice subjected to partial nephrectomy. If confirmed in humans, the oxidative state of adipocytes may be a therapeutic target in chronic renal failure.

Obesity has become a worldwide epidemic. We have previously reported that systemic administration of pNaKtide which targets the Na/K-ATPase oxidant amplification loop (NKAL) was able to decrease systemic oxidative stress and adiposity in mice fed a high fat and fructose supplemented western diet (WD). As adipocytes are believed to play a central role in the development of obesity and its related comorbidities, we examined whether lentiviral-mediated adipocyte-specific expression of NaKtide, a peptide derived from the N domain of the alpha1 Na/K-ATPase subunit, could ameliorate the effects of the WD. C57BL6 mice were fed a WD, which activated Na/K-ATPase signaling in the adipocytes and induced an obese phenotype and caused an increase in plasma levels of leptin, IL-6 and TNFα. WD also decreased locomotor activity, expression of the D2 receptor and tyrosine hydroxylase in brain tissue, while markers of neurodegeneration and neuronal apoptosis were increased following the WD. Selective adipocyte expression of NaKtide in these mice fed a WD attenuated all of these changes including the brain biochemical alterations and behavioral adaptations. These data suggest that adipocyte derived cytokines play an essential role in the development of obesity induced by a WD and that targeting the adipocyte NKAL loop may serve as an effective therapeutic strategy.

Reductions in the amount of haulm in peas would be of value to growers of vining peas and harvest peas. Two mutant forms of pea, the 'leafless pea' (afaf) and the 'reduced stipule pea' (stst), have been used in a breeding programme to develop lines with commercial potential. Four cultivars and 15 of these experimental lines have now been assessed for their agricultural potential in a yield trial.The results of the experiments indicate that these experimental phenotypes are at no disadvantage over conventional peas as regards their yield. A number of further possible advantages have become apparent during the process of crossing, selecting and evaluating these lines.

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Received i .vii.54 * Root tips for squash preparations were fixed in La Cour's 2 BD and after one hour an equal quantity of i per cent. chromic acid was added to this fixative. Next day the roots were thoroughly washed in distilled water and treated in s part 20 vol. hydrogen peroxide and 3 parts saturated solution of ammoniuxn oxalate for five minutes (Dr C. E. Ford, unpub.). The normal procedure for Feulgen squashes followed. OO5 per Cent. colchicine was used for the pre-treatment of root tips for some of the squash preparations. Roots for embedding were fixed in La Cour's 2 BD, embedded, sectioned at z6-i8 and stained with crystal violet. Pollen mother cells were treated as Feulgen squashes after fixation in acetic alcohol (s :