Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptome analysis in calorie-restricted rats implicates epigenetic and post-translational mechanisms in neuroprotection and aging

ABSTRACT: Using RNA-seq, 39 cerebral cortex RNA samples were sequenced. The study design was as follows: Ad libitum fed rats at 6 months (n=3, 6 individuals pooled), 12 months (n=3, 6 individuals pooled) and 28 months (n=3, 6 individuals pooled). Calorie restricted rats at 6 months (n=3, 6 individuals pooled), 12 months (n=3, 6 individuals pooled) and 28 months (n=3, 6 individuals pooled). Rats fed alpha lipoic acid as a supplement to ad libitum at 12 months (n=3, 6 individuals pooled) and 28 months (n=3, 6 individuals pooled). Diet switching groups, where diet was changes at 12 months; 28 month ad libitum switched to calorie restriction (n=3, 6 individuals pooled), 28 month calorie restriction switched to ad libitum (n=3, 6 individuals pooled), 28 month ad libitum plus lipoic acid switched to calorie restriction (n=3, 6 individuals pooled), 28 month calorie restriction switched to ad libitum plus lipoic acid (n=3, 6 individuals pooled). Transcriptional profiling of the ageing cerebral cortex at 6, 12 and 28 months and the effect of diet on age and longevity, using carlorie restriction and alpha lipoic acid supplementation

ORGANISM(S): Rattus norvegicus

SUBMITTER: Shona Wood

PROVIDER: E-GEOD-57110 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Rodents are commonly housed below thermoneutrality (~20°C) 1. Under these conditions there is a substantial effect on rodent physiology including the hyperactivation of brown (BAT) and beige adipose tissue 2. Here, we raised animals from weaning, on an obesogenic diet at thermoneutrality (28°C) to closer mimic human physiology and determine the impact of a) moderate cold exposure (i.e. 20°C, a temperature reduction of ~8°C) or b) treatment with YM-178, a highly-selective, clinically used β3-adrenoreceptor agonist on classical BAT or subcutaneous inguinal (IWAT) beige depots. Under these conditions, uncoupling protein 1 mRNA was undetectable in IWAT in all groups. Maintenance at 20°C drove weight gain and a 125% increase in subcutaneous fat, an effect not seen with YM-178 administration thus suggesting a direct effect of ambient temperature in promoting weight gain and adiposity in obese rats. Using exploratory adipose tissue proteomics we reveal novel processes and pathways associated with cold-induced weight gain in BAT (i.e. histone deacetylation and glycosphingolipid biosynthesis) and IWAT (i.e. NAD+ binding and retinol metabolism). Conversely, YM-178 had minimal metabolic-related effects on BAT and drove a pro-inflammatory phenotype in IWAT. Exercise training elicits diverse effects on brown (BAT) and white adipose tissue (WAT) physiology in rodents housed below their thermoneutral zone (i.e. 28-32°C). In these conditions, BAT is chronically hyperactive and, unlike human residence, closer to thermoneutrality. Therefore, we set out to determine the effects of exercise training in obese animals at 28°C (i.e. thermoneutrality) on BAT and WAT in its basal (i.e. inactive) state. Sprague-Dawley rats (n=12) were housed at thermoneutrality from 3 weeks of age and fed a high-fat diet. At 12 weeks of age half these animals were randomised to 4-weeks of swim-training (1 hour/day, 5 days per week). Following a metabolic assessment interscapular and perivascular BAT and inguinal (I)WAT were taken for analysis of thermogenic genes and the proteome. Exercise attenuated weight gain but did not affect total fat mass or thermogenic gene expression. Proteomics revealed an impact of exercise training on2-oxoglutarate metabolic process, mitochondrial respiratory chain complex IV, carbon metabolism and oxidative phosphorylation. This was accompanied by an upregulation of multiple proteins involved in skeletal muscle physiology suggesting an adipocyte to myocyte switch in BAT. UCP1 mRNA was undetectable in IWAT with proteomics highlighting changes to DNA binding, the positive regulation of apoptosis, HIF-1 signalling and cytokine-cytokine receptor interaction.

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Transcriptome analysis in calorie-restricted rats implicates epigenetic and post-translational mechanisms in neuroprotection and aging

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