COL6A3 expression in adipose tissue cells is associated with levels of the homeobox transcription factor PRRX1

Fibrillar collagen COL6α3 in adipose tissue has been associated with obesity, inflammation, insulin resistance and cancer. We here aimed to identify novel transcriptional regulators of COL6A3 expression. Based on a transcriptome dataset of adipose tissue, we identified strong correlations for 56 genes with COL6A3 mRNA, including targets of TGF-β/SMAD signaling. Among the identified candidates, the homeobox transcription factor PRRX1 showed a particularly striking co-expression with COL6A3, validated across several different cohorts, including patients with extreme obesity, insulin sensitive and resistant obesity (subcutaneous and omental), after profound fat loss (subcutaneous), and lean controls (subcutaneous). In human and mouse adipose cells, PRRX1 knockdown reduced COL6A3 mRNA and PRRX1 overexpression transactivated a reporter construct with the endogenous human COL6A3 promoter. Stable PRRX1 overexpression in 3T3-L1 cells induced Col6a3 mRNA threefold specifically after adipogenic induction, whereas TGF-β1 treatment upregulated Col6a3 mRNA also in the preadipocyte state. Interestingly, pro-inflammatory stimulus (i.e., TNF-α treatment) decreased PRRX1-mediated Col6a3 transactivation and mRNA expression, supporting a role for this mechanism in the regulation of adipose tissue inflammation. In conclusion, we identified the homeobox factor PRRX1 as a novel transcriptional regulator associated with COL6A3 expression, providing new insight into the regulatory mechanisms of altered adipose tissue function in obesity and insulin resistance.publishedVersio

Long-Term Exposure to Wind Turbine Noise and Risk for Myocardial Infarction and Stroke:A Nationwide Cohort Study

Background: Noise from wind turbines (WTs) is reported as more annoying than traffic noise at similar levels, raising concerns as to whether WT noise (WTN) increases risk for cardiovascular disease, as observed for traffic noise. Objectives: We aimed to investigate whether long-term exposure to WTN increases risk of myocardial infarction (MI) and stroke. Methods: We identified all Danish dwellings within a radius 20 times the height of the closest WT and 25% of the dwellings within 20–40 times the height of the closest WT. Using data on WT type and simulated hourly wind at each WT, we estimated hourly outdoor and low frequency (LF) indoor WTN for each dwelling and derived 1-y and 5-y running nighttime averages. We used hospital and mortality registries to identify all incident cases of MI (n=19,145) and stroke (n=18,064) among all adults age 25–85 y (n=717,453), who lived in one of these dwellings for ≥one year over the period 1982–2013. We used Poisson regression to estimate incidence rate ratios (IRRs) adjusted for individual- and area-level covariates. Results: IRRs for MI in association with 5-y nighttime outdoor WTN ˃42 (vs. ˂24) dB(A) and indoor LF WTN ˃15 (vs. ˂5) dB(A) were 1.21 [95% confidence interval (CI): 0.91, 1.62; 47 exposed cases] and 1.29 (95% CI: 0.73, 2.28; 12 exposed cases), respectively. IRRs for intermediate categories of outdoor WTN [24–30, 30–36, and 36–42 dB(A) vs. ˂24 dB(A)] were slightly above the null and of similar size: 1.08 (95% CI: 1.04, 1.12), 1.07 (95% CI: 1.00, 1.12), and 1.06 (95% CI: 0.93, 1.22), respectively. For stroke, IRRs for the second and third outdoor exposure groups were similar to those for MI, but near or below the null for higher exposures. Conclusions: We did not find convincing evidence of associations between WTN and MI or stroke.</p

Short-term effects of Vertical sleeve gastrectomy and Roux-en-Y gastric bypass on glucose homeostasis

The objective of this study was to compare the biochemical changes related to glucose tolerance and lipid metabolism in non-diabetic patients shortly after vertical sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). Non-diabetic women and men with morbid obesity were studied the day before and six days after SG (N = 15) or RYGB (N = 16). Patients completed an oral glucose tolerance test (OGTT; 75 g glucose) at both visits. SG and RYGB similarly improved fasting glucose homeostasis six days after surgery, with reduced glucose and insulin concentrations. The OGTT revealed differences between the two surgery groups that were not evident from the fasting serum concentrations. Postprandial (120 min) glucose and insulin concentrations were lower after RYGB but not after SG, whereas concentrations of glucagon-like peptide-1, peptide YY, glucagon and non-esterified fatty acids were elevated after both SG and RYGB. Fasting triacylglycerol concentration did not change after surgery, but concentrations of high density lipoprotein and low density lipoprotein cholesterols were reduced in both surgery groups, with no differences between the groups. To conclude, RYGB induced a more pronounced improvement in postprandial glucose homeostasis relative to SG, possibly due to improved insulin sensitivity rather than augmented insulin concentration.publishedVersio

Impact of Long-Term Exposure to Wind Turbine Noise on Redemption of Sleep Medication and Antidepressants: A Nationwide Cohort Study

Background: Noise from wind turbines (WTs) is associated with annoyance and, potentially, sleep disturbances. Objectives: Our objective was to investigate whether long-term WT noise (WTN) exposure is associated with the redemption of prescriptions for sleep medication and antidepressants. Methods: For all Danish dwellings within a radius of 20-WT heights and for 25% of randomly selected dwellings within a radius of 20-to 40-WT heights, we estimated nighttime outdoor and low-frequency (LF) indoor WTN, using information on WT type and simulated hourly wind. During follow-up from 1996 to 2013, 68,696 adults redeemed sleep medication and 82,373 redeemed antidepressants, from eligible populations of 583,968 and 584,891, respectively. We used Poisson regression with adjustment for individual and area-level covariates. Results: Five-year mean outdoor nighttime WTN of ≥42 dB was associated with a hazard ratio (HR) = 1.14 [95% confidence interval (CI]: 0.98, 1.33) for sleep medication and HR = 1.17 (95% CI: 1.01, 1.35) for antidepressants (compared with exposure to WTN of ˂24 dB). We found no overall association with indoor nighttime LF WTN. In age-stratified analyses, the association with outdoor nighttime WTN was strongest among persons ≥65y of age, with HRs (95% CIs) for the highest exposure group (≥42 dB) of 1.68 (1.27, 2.21) for sleep medication and 1.23 (0.90, 1.69) for antidepressants. For indoor nighttime LF WTN, the HRs (95% CIs) among persons ≥65y of age exposed to ≥15 dB were 1.37 (0.81, 2.31) for sleep medication and 1.34 (0.80, 2.22) for antidepressants. Conclusions: We observed high levels of outdoor WTN to be associated with redemption of sleep medication and antidepressants among the elderly, suggesting that WTN may potentially be associated with sleep and mental health.</p