Dichotomous effects of VEGF-A on adipose tissue dysfunction

Obese fat pads are frequently undervascularized and hypoxic, leading to increased fibrosis, inflammation, and ultimately insulin resistance. We hypothesized that VEGF-A-induced stimulation of angiogenesis enables sustained and sufficient oxygen and nutrient exchange during fat mass expansion, thereby improving adipose tissue function. Using a doxycycline (Dox)-inducible adipocyte-specific VEGF-A overexpression model, we demonstrate that the local up-regulation of VEGF-A in adipocytes improves vascularization and causes a "browning" of white adipose tissue (AT), with massive up-regulation of UCP1 and PGC1 alpha. This is associated with an increase in energy expenditure and resistance to high fat diet-mediated metabolic insults. Similarly, inhibition of VEGF-A-induced activation of VEGFR2 during the early phase of high fat diet-induced weight gain, causes aggravated systemic insulin resistance. However, the same VEGF-A-VEGFR2 blockade in ob/ob mice leads to a reduced body-weight gain, an improvement in insulin sensitivity, a decrease in inflammatory factors, and increased incidence of adipocyte death. The consequences of modulation of angiogenic activity are therefore context dependent. Proangiogenic activity during adipose tissue expansion is beneficial, associated with potent protective effects on metabolism, whereas antiangiogenic action in the context of preexisting adipose tissue dysfunction leads to improvements in metabolism, an effect likely mediated by the ablation of dysfunctional proinflammatory adipocytes.National Institutes of HealthNational Institutes of Health [R01-DK55758, RC1DK086629, P01DK088761

SLC26A1 is a major determinant of sulfate homeostasis in humans

Sulfate plays a pivotal role in numerous physiological processes in the human body, including bone and cartilage health. A role of the anion transporter SLC26A1 (Sat1) for sulfate reabsorption in the kidney is supported by the observation of hyposulfatemia and hypersulfaturia in Slc26a1-knockout mice. The impact of SLC26A1 on sulfate homeostasis in humans remains to be defined. By combining clinical genetics, functional expression assays, and population exome analysis, we identify SLC26A1 as a sulfate transporter in humans and experimentally validate several loss-of-function alleles. Whole-exome sequencing from a patient presenting with painful perichondritis, hyposulfatemia, and renal sulfate wasting revealed a homozygous mutation in SLC26A1, which has not been previously described to the best of our knowledge. Whole-exome data analysis of more than 5,000 individuals confirmed that rare, putatively damaging SCL26A1 variants were significantly associated with lower plasma sulfate at the population level. Functional expression assays confirmed a substantial reduction in sulfate transport for the SLC26A1 mutation of our patient, which we consider to be novel, as well as for the additional variants detected in the population study. In conclusion, combined evidence from 3 complementary approaches supports SLC26A1 activity as a major determinant of sulfate homeostasis in humans. In view of recent evidence linking sulfate homeostasis with back pain and intervertebral disc disorder, our study identifies SLC26A1 as a potential target for modulation of musculoskeletal health

Levelling off of prevalence of obesity in the adult population of Sweden between 2000/01 and 2004/05

<p>Abstract</p> <p>Background</p> <p>The escalating global epidemic of obesity is of worldwide concern because of its association with several chronic diseases and premature mortality. Some subgroups seem to be more affected than others. The aim of this study was to examine whether the mean BMI (adjusted for age) and the prevalence of obesity (adjusted for all the explanatory variables) changed between 2000/01 and 2004/05 in different subgroups of the Swedish population.</p> <p>Methods</p> <p>This study compared two cross-sectional, nationwide random samples of persons aged 16 to 84 years: the first from 2000/01 (5515 men, 5838 women) and the second from 2004/05 (4681 men, 4821 women). After stratification by gender, a logistic regression model was applied to analyse possible changes in mean BMI and the prevalence of obesity between 2000/01 and 2004/05.</p> <p>Results</p> <p>Total mean BMI remained almost unchanged between 2000/01 and 2004/05 for both men and women. The prevalence of obesity increased slightly in both men and women, but not significantly (from 9.7 to 10.8% and from 9.6 to 10.2%, respectively). The prevalence of obesity in 2004/05 was especially high in some subgroups: men aged 45-54 (14.3%) or 55-64 (16.5%), women aged 65-74 (15.9%) or 75-84 (16.8%), men and women of middle educational level (15.6% and 14.4%, respectively), male former smokers (13.4%), and men from small towns or rural areas (13.1%).</p> <p>Conclusions</p> <p>Although the mean BMI and obesity were almost unchanged in the Swedish adult population between 2000/01 and 2004/05, obesity levels in Sweden remained unacceptably high, especially in certain subgroups. Primary and secondary intervention actions should strive to decrease the prevalence of obesity in Sweden.</p

TonEBP suppresses adipogenesis and insulin sensitivity by blocking epigenetic transition of PPAR gamma 2

TonEBP is a key transcription factor in cellular adaptation to hypertonic stress, and also in macrophage activation. Since TonEBP is involved in inflammatory diseases such as rheumatoid arthritis and atherosclerosis, we asked whether TonEBP played a role in adipogenesis and insulin resistance. Here we report that TonEBP suppresses adipogenesis and insulin signaling by inhibiting expression of the key transcription factor PPAR gamma 2. TonEBP binds to the PPAR gamma 2 promoter and blocks the epigenetic transition of the locus which is required for the activation of the promoter. When TonEBP expression is reduced, the epigenetic transition and PPAR gamma 2 expression are markedly increased leading to enhanced adipogenesis and insulin response while inflammation is reduced. Thus, TonEBP is an independent determinant of adipose insulin sensitivity and inflammation. TonEBP is an attractive therapeutic target for insulin resistance in lieu of PPAR gamma agonistsopen0

Dietary differences between elderly Iranians living in Sweden and Iran a cross-sectional comparative study

<p>Abstract</p> <p>Background</p> <p>During the last decades, global migration has increased and many immigrant groups have a higher prevalence than the native born population of several cardiovascular disease risk factors, including poor dietary habits. However, it is uncertain if dietary habits in immigrant populations reflect dietary habits in their country of origin or if the current diet is a consequence of the migration and possible change of dietary habits. The aim of this study was to examine possible dietary differences between elderly Iranians living in Stockholm, Sweden with elderly Iranians living in Tehran, Iran, taking into account sex, age, marital status, and education.</p> <p>Methods</p> <p>Dietary intakes were assessed by semi - quantitative food frequency questionnaire in a cross-sectional study of 121 Iranians living in Stockholm and 52 Iranians living in Tehran, aged 60-80. Differences in dietary habits between the two groups was analysed by bootstrapped regression analyses with 1000 replications.</p> <p>Results</p> <p>Iranians living in Sweden had significantly higher intake of protein, total fat, fiber than Iranians living in Iran, but lower consumption of carbohydrates. The observed differences in intake of macronutrients were reflected in consumed amount of all food items, which were higher among Iranians living in Iran with the exception of bread and grain consumption which was lower.</p> <p>Conclusions</p> <p>There are general differences in dietary habits between Iranians living in Iran and Iranians living in Sweden. Parts of observed differences in dietary habits may reflect a favourable adoption process to the Swedish dietary habits after migration. Meanwhile other differences are point of concern in light of the high prevalence of overweight, among Iranians living in Sweden and can have unfavourable impact in particular in the context of cardiovascular health.</p