Genetic aspects of susceptibility to obesity and related dyslipidemias

Obesity has a multifactorial origin. However, although environmental variables undoubtedly play a role in the development of obesity, it is now clear that genetic variation is also involved in the determination of an individual's susceptibility to body fat accumulation. In addition, it is also widely accepted that obesity is not a single homogeneous phenotype. It is also heterogeneous regarding its causes and metabolic complications. The regional distribution of body fat appears to be an important correlate of the metabolic complications that have been related to obesity. Due to their higher accumulation of abdominal fat, men are generally more at risk for the metabolic complications of obesity than women whereas some obese women, with large gluteal-femoral adipose depots may have a cosmetic problem which may not necessarily require medical intervention. Several studies have been conducted to understand the mechanisms by which abdominal obesity is related to diabetes, hypertension and cardiovascular disease. It appears that the increased risk of abdominal obesity is the result of complex hormonal and metabolic interactions. Studies in genetic epidemiology have shown that both total body fatness and the regional distribution of body fat have a significant genetic component. Standardized intervention studies using an identical twin design have shown that individuals that have the same genetic background tend to show similar changes in body fat and in plasma lipoprotein levels when exposed to standardized caloric excess or energy restriction. Finally, although abdominal obesity is a significant risk factor for cardiovascular disease, not every abdominal obese subject will experience metabolic complications, suggesting that some obese individuals may be more susceptible than others. Variation in several genes relevant to lipid and lipoprotein metabolism may alter the relation of abdominal obesity to dyslipoproteinemias. Abdominal obesity should therefore be considered as a factor that exacerbates an individual's susceptibility to cardiovascular disease.     

The Influence of Anatomical Boundaries,Age, and Sex on the Assessment of Abdominal Visceral Fat

CLASEY, JODY L, CLAUDE BOUCHARD, LAURIE WIDEMAN, JILL KANALEY, C DAVID TEATES, MICHAEL O THORNER, MARK L HARTMAN, ARTHUR WELTMAN. The influence of anatomical boundaries, age, and sex on the assessment of abdominal visceral fat. Single-slice abdominal computed tomography (CT) scanning has been used extensively for the measurement of abdominal visceral fat (AYF). Optimal anatomical scan location and pixel density ranges have been proposed and are specifically reported to allow for the replication and standardization of AVF measurements. Standardization of the anatomical boundaries for CT measurement of AVF and the influence of age and gender on results obtained with different boundary locations have received much less attention. To determine the influence of three boundary analysis methods (AVF-1, AVF-2, and AVF-3) on the measurement of AVF by CT, 54 older (60 years to 79 years) and 37 younger (20 years to 29 years) healthy men and women were examined. The measurement boundary for AVF-1 was the internal most aspect of the abdominal and oblique muscle walls, and the posterior aspect of the vertebral body. AVF-2 used fat measurements enclosed in a boundary formed by the midpoint of the abdominal and oblique muscle walls, and the most posterior aspect of the spinous process. AVF-3 used fat measurements enclosed in a boundary formed by the external border of the abdominal and oblique muscle walls, and the external border of the erector spinae. Greater AVF measures were obtained with AVF-2 and AVF-3 compared with AVF-1 (p<0.0001). These differences were greater in older compared with younger subjects (p<0.0001) and greater in women compared with men (p<0.02). The significantly greater AVF measurements obtained with AVF-2 and AVF-3 resulted from the inclusion of larger amounts of fat that are not drained by the portal circulation. This included retroperitoneal, intermuscular, and intramuscular lipid droplets, which increase with aging. On the basis of these results, we recommend the AVF-1 anatomical boundaries for the measurement of AVF in clinical investigations, particularly with older subjects. These data demonstrate the importance of precise and reproducible anatomical boundaries for the measurement of AVF, particularly in longitudinal studies.     

Ezrin/Radixin/Moesin Are Required for the Purinergic P2X7 Receptor (P2X7R)-dependent Processing of the Amyloid Precursor Protein

The amyloid precursor protein (APP) can be cleaved by α-secretases in neural cells to produce the soluble APP ectodomain (sAPPα), which is neuroprotective. We have shown previously that activation of the purinergic P2X7 receptor (P2X7R) triggers sAPPα shedding from neural cells. Here, we demonstrate that the activation of ezrin, radixin, and moesin (ERM) proteins is required for the P2X7R-dependent proteolytic processing of APP leading to sAPPα release. Indeed, the down-regulation of ERM by siRNA blocked the P2X7R-dependent shedding of sAPPα. We also show that P2X7R stimulation triggered the phosphorylation of ERM. Thus, ezrin translocates to the plasma membrane to interact with P2X7R. Using specific pharmacological inhibitors, we established the order in which several enzymes trigger the P2X7R-dependent release of sAPPα. Thus, a Rho kinase and the MAPK modules ERK1/2 and JNK act upstream of ERM, whereas a PI3K activity is triggered downstream. For the first time, this work identifies ERM as major partners in the regulated non-amyloidogenic processing of APP.     

Orosomucoid,a New Biomarker in the Association between Obesity and Periodontitis

Epidemiological data indicate an association between periodontitis and obesity. The biological mechanisms of this relationship remain unclear. A cross-sectional study was conducted to evaluate the relationship between periodontitis and the common systemic inflammatory markers in 32 morbidly obese patients recruited in a Clinical Nutrition department. Periodontal condition was evaluated using pocket depth (PD) measurement, a classical clinical marker of ongoing periodontitis. Major periodontal risk factors were recorded (age, gender, diabetes and smoking status), as well as plasma levels of inflammatory markers (CRP, orosomucoid, IL-6) and adipokines (adiponectin, leptin). All patients included in the sample exhibited evidence of periodontitis, 16 of whom were diagnosed as having severe disease. Adjusted logistic regression analysis indicated that the severity of periodontitis was associated with the plasma level of orosomucoid (p<0.04) after adjustment for age, gender and smoking. Our study thus suggests that the severity of periodontitis, in morbidly obese patients, is associated with the increase of orosomucoid levels.     

Diversity of Chironomidae (Diptera) along a salinity gradient in lakes of the endorheic Great Lakes region of western Mongolia

Hydrobiologia - The Great Lakes region of western Mongolia includes a diversity of lake ecosystems, from alpine freshwater to lowland, saline lakes, which increasingly face environmental threats...     

Introduction pathways of economically costly invasive alien species

Biological Invasions - Introduction pathways play a pivotal role in the success of Invasive Alien Species (IAS)—the subset of alien species that have a negative environmental and/or...     

The influence of native populations’ genetic history on the reconstruction of invasion routes: the case of a highly invasive aquatic species

Biological Invasions - Insufficient data on the origins of the first introduced propagule and the initial stages of invasion complicate the reconstruction of a species’ invasion history....     

An Adapting Auditory-motor Feedback Loop Can Contribute to Generating Vocal Repetition

Consecutive repetition of actions is common in behavioral sequences. Although integration of sensory feedback with internal motor programs is important for sequence generation, if and how feedback contributes to repetitive actions is poorly understood. Here we study how auditory feedback contributes to generating repetitive syllable sequences in songbirds. We propose that auditory signals provide positive feedback to ongoing motor commands, but this influence decays as feedback weakens from response adaptation during syllable repetitions. Computational models show that this mechanism explains repeat distributions observed in Bengalese finch song. We experimentally confirmed two predictions of this mechanism in Bengalese finches: removal of auditory feedback by deafening reduces syllable repetitions; and neural responses to auditory playback of repeated syllable sequences gradually adapt in sensory-motor nucleus HVC. Together, our results implicate a positive auditory-feedback loop with adaptation in generating repetitive vocalizations, and suggest sensory adaptation is important for feedback control of motor sequences.