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Träfflista för sökning "WFRF:(Sheldon E.) srt2:(2005-2009)"

Sökning: WFRF:(Sheldon E.) > (2005-2009)

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  • Lelliott, Christopher J., et al. (författare)
  • Ablation of PGC-1beta results in defective mitochondrial activity, thermogenesis, hepatic function, and cardiac performance
  • 2006
  • Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 4:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1beta (PGC-1beta) has been implicated in important metabolic processes. A mouse lacking PGC-1beta (PGC1betaKO) was generated and phenotyped using physiological, molecular, and bioinformatic approaches. PGC1betaKO mice are generally viable and metabolically healthy. Using systems biology, we identified a general defect in the expression of genes involved in mitochondrial function and, specifically, the electron transport chain. This defect correlated with reduced mitochondrial volume fraction in soleus muscle and heart, but not brown adipose tissue (BAT). Under ambient temperature conditions, PGC-1beta ablation was partially compensated by up-regulation of PGC-1alpha in BAT and white adipose tissue (WAT) that lead to increased thermogenesis, reduced body weight, and reduced fat mass. Despite their decreased fat mass, PGC1betaKO mice had hypertrophic adipocytes in WAT. The thermogenic role of PGC-1beta was identified in thermoneutral and cold-adapted conditions by inadequate responses to norepinephrine injection. Furthermore, PGC1betaKO hearts showed a blunted chronotropic response to dobutamine stimulation, and isolated soleus muscle fibres from PGC1betaKO mice have impaired mitochondrial function. Lack of PGC-1beta also impaired hepatic lipid metabolism in response to acute high fat dietary loads, resulting in hepatic steatosis and reduced lipoprotein-associated triglyceride and cholesterol content. Altogether, our data suggest that PGC-1beta plays a general role in controlling basal mitochondrial function and also participates in tissue-specific adaptive responses during metabolic stress.
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  • Jones, Owen R., et al. (författare)
  • Senescence rates are determined by ranking on the fast-slow life-history continuum
  • 2008
  • Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 11:7, s. 664-673
  • Tidskriftsartikel (refereegranskat)abstract
    • Comparative analyses of survival senescence by using life tables have identified generalizations including the observation that mammals senesce faster than similar-sized birds. These generalizations have been challenged because of limitations of life-table approaches and the growing appreciation that senescence is more than an increasing probability of death. Without using life tables, we examine senescence rates in annual individual fitness using 20 individual-based data sets of terrestrial vertebrates with contrasting life histories and body size. We find that senescence is widespread in the wild and equally likely to occur in survival and reproduction. Additionally, mammals senesce faster than birds because they have a faster life history for a given body size. By allowing us to disentangle the effects of two major fitness components our methods allow an assessment of the robustness of the prevalent life-table approach. Focusing on one aspect of life history - survival or recruitment - can provide reliable information on overall senescence.
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