16 research outputs found
Correction to: Overexpression of Protein Kinase Inhibitor Alpha Reverses Rat Low Voluntary Running Behavior
Rapid Alterations in Perirenal Adipose Tissue Transcriptomic Networks with Cessation of Voluntary Running.
In maturing rats, the growth of abdominal fat is attenuated by voluntary wheel running. After the cessation of running by wheel locking, a rapid increase in adipose tissue growth to a size that is similar to rats that have never run (i.e. catch-up growth) has been previously reported by our lab. In contrast, diet-induced increases in adiposity have a slower onset with relatively delayed transcriptomic responses. The purpose of the present study was to identify molecular pathways associated with the rapid increase in adipose tissue after ending 6 wks of voluntary running at the time of puberty. Age-matched, male Wistar rats were given access to running wheels from 4 to 10 weeks of age. From the 10th to 11th week of age, one group of rats had continued wheel access, while the other group had one week of wheel locking. Perirenal adipose tissue was extracted, RNA sequencing was performed, and bioinformatics analyses were executed using Ingenuity Pathway Analysis (IPA). IPA was chosen to assist in the understanding of complex 'omics data by integrating data into networks and pathways. Wheel locked rats gained significantly more fat mass and significantly increased body fat percentage between weeks 10-11 despite having decreased food intake, as compared to rats with continued wheel access. IPA identified 646 known transcripts differentially expressed (p < 0.05) between continued wheel access and wheel locking. In wheel locked rats, IPA revealed enrichment of transcripts for the following functions: extracellular matrix, macrophage infiltration, immunity, and pro-inflammatory. These findings suggest that increases in visceral adipose tissue that accompanies the cessation of pubertal physical activity are associated with the alteration of multiple pathways, some of which may potentiate the development of pubertal obesity and obesity-associated systemic low-grade inflammation that occurs later in life
Second scoring network inclusive of up-regulated genes (score = 40) in LOCK vs RUN.
<p>Nodes represent genes/molecules. Shading is proportional to fold change size (red: upregulated). Direct and indirect relationships are denoted with solid and dashed lines, respectively. White nodes denote network members that were not altered in the network. Lines ending in an arrow or blunt end indicate known direction of molecular activation or inhibition, respectively. Different shapes of genes represent different gene functions.</p
Top scoring network inclusive of genes expressed only in LOCK (score = 63).
<p>Nodes represent genes/molecules. Shading is proportional to RPKM value. Direct and indirect relationships are denoted with solid and dashed lines, respectively. White nodes denote network members that were not altered in the network. Lines ending in an arrow or blunt end indicate known direction of molecular activation or inhibition, respectively. Different shapes of genes represent different gene functions.</p
PRAT adipocyte size distribution.
<p>Adipocyte diameters were classified in 10-μm categories [category #, adipocyte diameter range in μm (10: 0.0–9.0μm, 20: 10.0–19.9μm, 20: 20.0–29.9μm, etc.] on the x-axis; and the percentage of total adipocytes in a 10-μm category was plotted on y-axis. At least 300 adipocyte diameters were measured for each tissue sample. Different letters denote differences among groups at each 10-μm category, p<0.05, as determined by Student’s t-test.</p
Daily food intake over the final 14 days.
<p>The vertical dashed line represents the day of wheel locking (LOCK). Different letters denote significance among groups at p < 0.05, as determined by Student’s t-test.</p
Protein expression of A) Col1a1 and B) Cd36 in PRAT from continued wheel access (RUN) and wheel locking (LOCK) rats (n = 5 per group).
<p>Protein expression was normalized for Ponceau S.</p
TFAM Enhances Fat Oxidation and Attenuates High Fat Diet Induced Insulin Resistance in Skeletal Muscle
Left ventricle transcriptomic analysis reveals connective tissue accumulation associates with initial age-dependent decline in V̇ o
Brain functions and cognition on transient insulin deprivation in type 1 diabetes
BACKGROUND Type 1 diabetes (T1D) is a risk factor for dementia and structural brain changes. It remains to be determined whether transient insulin deprivation that frequently occurs in insulin-treated individuals with T1D alters brain function.METHODS We therefore performed functional and structural magnetic resonance imaging, magnetic resonance spectroscopy, and neuropsychological testing at baseline and following 5.4 ± 0.6 hours of insulin deprivation in 14 individuals with T1D and compared results with those from 14 age-, sex-, and BMI-matched nondiabetic (ND) participants with no interventions.RESULTS Insulin deprivation in T1D increased blood glucose, and β-hydroxybutyrate, while reducing bicarbonate levels. Participants with T1D showed lower baseline brain N-acetyl aspartate and myo-inositol levels but higher cortical fractional anisotropy, suggesting unhealthy neurons and brain microstructure. Although cognitive functions did not differ between participants with T1D and ND participants at baseline, significant changes in fine motor speed as well as attention and short-term memory occurred following insulin deprivation in participants with T1D. Insulin deprivation also reduced brain adenosine triphosphate levels and altered the phosphocreatine/adenosine triphosphate ratio. Baseline differences in functional connectivity in brain regions between participants with T1D and ND participants were noted, and on insulin deprivation further alterations in functional connectivity between regions, especially cortical and hippocampus-caudate regions, were observed. These alterations in functional connectivity correlated to brain metabolites and to changes in cognition.CONCLUSION Transient insulin deprivation therefore caused alterations in executive aspects of cognitive function concurrent with functional connectivity between memory regions and the sensory cortex. These findings have important clinical implications, as many patients with T1D inadvertently have periods of transient insulin deprivation.TRIAL REGISTRATION ClinicalTrials.gov NCT03392441.FUNDING Clinical and Translational Science Award (UL1 TR002377) from the National Center for Advancing Translational Science; NIH grants (R21 AG60139 and R01 AG62859); the Mayo Foundation