Cardio-metabolic risk factors and prehypertension in persons without diabetes, hypertension, and cardiovascular disease

10.1186/1471-2458-13-730BMC Public Health131

Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis

The development and severity of inflammatory bowel diseases and other chronic inflammatory conditions can be influenced by host genetic and environmental factors, including signals derived from commensal bacteria. However, the mechanisms that integrate these diverse cues remain undefined. Here we demonstrate that mice with an intestinal epithelial cell (IEC)-specific deletion of the epigenome-modifying enzyme histone deacetylase 3 (HDAC3(ΔIEC) mice) exhibited extensive dysregulation of IEC-intrinsic gene expression, including decreased basal expression of genes associated with antimicrobial defence. Critically, conventionally housed HDAC3(ΔIEC) mice demonstrated loss of Paneth cells, impaired IEC function and alterations in the composition of intestinal commensal bacteria. In addition, HDAC3(ΔIEC) mice showed significantly increased susceptibility to intestinal damage and inflammation, indicating that epithelial expression of HDAC3 has a central role in maintaining intestinal homeostasis. Re-derivation of HDAC3(ΔIEC) mice into germ-free conditions revealed that dysregulated IEC gene expression, Paneth cell homeostasis and intestinal barrier function were largely restored in the absence of commensal bacteria. Although the specific mechanisms through which IEC-intrinsic HDAC3 expression regulates these complex phenotypes remain to be determined, these data indicate that HDAC3 is a critical factor that integrates commensal-bacteria-derived signals to calibrate epithelial cell responses required to establish normal host-commensal relationships and maintain intestinal homeostasis

Prevalence and correlates of hyperglycemia in a rural population, Vietnam: implications from a cross–sectional study

<p>Abstract</p> <p>Background</p> <p>Despite the increasing prevalence of type 2 diabetes in urban areas, relatively little has been known about its actual prevalence and its associations in rural areas, Vietnam. The purpose of this study was to evaluate the prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), diabetes and their risk factors in a rural province, Vietnam.</p> <p>Methods</p> <p>A cross–sectional study with a representative sample was designed to estimate the hyperglycemia prevalence, using 75–g oral glucose tolerance test. Potential risk factors for hyperglycemia were analyzed using multinomial logistic regression, taken into account influences of socio–economic status, anthropometric measures, and lifestyle–related factors.</p> <p>Results</p> <p>The age and sex–adjusted prevalence rates (95% CI) of isolated IFG, isolated IGT, combined IFG–IGT, and diabetes were 8.7 (7.0–10.5), 4.3 (3.2−5.4), 1.6 (0.9−2.3), and 3.7% (2.7–4.7%), respectively. There were still 73% of diabetic subjects without knowing the condition. Blood pressure, family history of diabetes, obesity–related measures (waist circumference, waist–hip ratio, body fat percentage, and abdominal obesity) were the independent risk factors for hyperglycemia (IFG, IGT, and diabetes).</p> <p>Conclusions</p> <p>The prevalence of hyperglycemia in rural areas has not been as sharply increased as that reported in urban cities, Vietnam. Blood pressure and obesity–related measures were the most significant predictors for hyperglycemia level and they can be taken into account in building prognosis models to early detection of diabetes in rural Vietnamese populations.</p

Nur77 deletion impairs muscle growth during developmental myogenesis and muscle regeneration in mice

Muscle atrophy is a prevalent condition in illness and aging. Identifying novel pathways that control muscle mass may lead to therapeutic advancement. We previously identified Nur77 as a transcriptional regulator of glycolysis in skeletal muscle. More recently, we showed that Nur77 expression also controls myofiber size in mice. It was unknown, however, whether Nur77's regulation of muscle size begins during developmental myogenesis or only in adulthood. To determine the importance of Nur77 throughout muscle growth, we examined myofiber size at E18.5, 3 weeks postnatal age, and in young adult mice. Using the global Nur77-/- mice, we showed that Nur77 deficiency reduced myofiber size as early as E18.5. The reduction in myofiber size became more pronounced by 3 weeks of age. We observed comparable reduction in myofiber size in young myofiber-specific Nur77-knockout mice. These findings suggest that Nur77's effect on muscle growth is intrinsic to its expression in differentiating myofibers, and not dependent on its expression in myogenic stem cells. To determine the importance of Nur77 expression in muscle accretion in mature mice, we generated an inducible-, muscle-specific, Nur77-deficient mouse model. We demonstrated that tamoxifen-induced deletion of Nur77 in 3-month-old mice reduced myofiber size. This change was accompanied by increased activity of Smad2 and FoxO3, two negative regulators of muscle mass. The role of Nur77 in muscle growth was further elaborated in the cardiotoxin-induced muscle regeneration model. Compared to wildtype mice, regenerated myofibers were smaller in Nur77-/- mice. However, when normalized to saline-injected muscle, the recovery of sarcoplasmic area was comparable between Nur77-/- and wildtype mice. These findings suggest that Nur77 deficiency compromises myofiber growth, but not the regenerative capacity of myogenic progenitor cells. Collectively, the findings presented here demonstrate Nur77 as an important regulator of muscle growth both during prenatal and postnatal myogenesis