Rui Tao Wang

Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons

Objective Adiponectin receptors (AdipoRs) are located on neurons of the hypothalamus involved in metabolic regulation – including arcuate proopiomelanocortin (Pomc) and Neuropeptide Y/Agouti-related peptide (NPY/AgRP) neurons. AdipoRs play a critical role in regulating glucose and fatty acid metabolism by initiating several signaling cascades overlapping with Leptin receptors (LepRs). However, the mechanism by which adiponectin regulates cellular activity in the brain remains undefined. Methods In order to resolve this issue, we utilized neuron-specific transgenic mouse models to identify Pomc and NPY/AgRP neurons which express LepRs for patch-clamp electrophysiology experiments. Results We found that leptin and adiponectin synergistically activated melanocortin neurons in the arcuate nucleus. Conversely, NPY/AgRP neurons were inhibited in response to adiponectin. The adiponectin-induced depolarization of arcuate Pomc neurons occurred via activation of Phosphoinositide-3-kinase (PI3K) signaling, independent of 5′ AMP-activated protein kinase (AMPK) activity. Adiponectin also activated melanocortin neurons at various physiological glucose levels. Conclusions Our results demonstrate a requirement for PI3K signaling in the acute adiponectin-induced effects on the cellular activity of arcuate melanocortin neurons. Moreover, these data provide evidence for PI3K as a substrate for both leptin and adiponectin to regulate energy balance and glucose metabolism via melanocortin activity.

TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons

The molecular mechanisms underlying acute leptin and serotonin 2C receptor-induced hypophagia remain unclear. Here, we show that neuronal and pro-opiomelanocortin (Pomc)-specific loss of transient receptor potential cation 5 (TrpC5) subunits is sufficient to decrease energy expenditure and increase food intake resulting in elevated body weight. Deficiency of Trpc5 subunits in Pomc neurons is also sufficient to block the anorexigenic effects of leptin and serotonin 2C receptor (Ht2Cr) agonists. The loss of acute anorexigenic effects of these receptors is concomitant with a blunted electrophysiological response to both leptin and Ht2Cr agonists in arcuate Pomc neurons. We also demonstrate that the Ht2Cr agonist lorcaserin-induced improvements in glucose and insulin tolerance are blocked by TrpC5 deficiency in Pomc neurons. Together, our results link TrpC5 subunits in the brain with leptin- and serotonin 2C receptor-dependent changes in neuronal activity, as well as energy balance, feeding behavior, and glucose metabolism.

Elevated mean platelet volume is associated with silent cerebral infarction

The presence of silent cerebral infarction (SCI) increases the risk of transient ischaemia attack, symptomatic stroke, cardiovascular disease and dementia. Mean platelet volume (MPV) is a surrogate marker of activated platelets and is considered a link between inflammation and thrombosis. In addition, MPV is a risk predictor for cardiovascular disease, stroke and overall vascular mortality.

Neutrophil–Lymphocyte ratio is associated with arterial stiffness in diabetic retinopathy in type 2 diabetes

AIMS Diabetic retinopathy (DR) is the most common complication of type 2 diabetes mellitus (T2DM). Inflammation plays a considerable role in the pathogenesis of T2DM and DR. Emerging evidence revealed that the neutrophil-lymphocyte ratio (NLR) may be a useful marker of cardiovascular disease. The brachial-ankle pulse wave velocity (baPWV) is an indicator for early atherosclerotic changes. Therefore, this study aimed to investigate the association of NLR with baPWV in patients with DR. METHODS In this cross-sectional study, we investigated the relationship between NLR and baPWV in 402 participants. Participants were divided into the following three groups: 133 control subjects without T2DM; 138 diabetic subjects without DR; and 131 patients with DR. RESULTS NLR and baPWV were elevated both in T2DM and in DR. Moreover, compared to T2DM, NLR and baPWV were higher in DR. There was a positive correlation between NLR and baPWV in patients with T2DM and DR after adjusting confounding factors. Multiple linear regression analysis further revealed that NLR was an independent and significant determinant for elevated baPWV (for T2DM, β=0.170; p=0.041; for DR, β=0.188; p=0.022, respectively). CONCLUSIONS The findings showed that NLR and baPWV are elevated both in T2DM and in DR. In addition, NLR is independently associated with baPWV. Early detection of abnormal NLR levels may be helpful for the search of subclinical atherosclerosis in patients with T2DM and DR.

Neutrophil-lymphocyte ratio is associated with arterial stiffness in postmenopausal women with osteoporosis

OBJECTIVE Systemic inflammation may be a common mechanism for the development of osteoporosis (OP) and atherosclerosis. Elevated arterial stiffness is an index of subclinical atherosclerosis. Recent studies found that neutrophil/lymphocyte ratio (NLR), is a useful marker of cardiovascular disease and a more powerful predictor than any other leukocyte subtypes. However, little research has been conducted to investigate the relationship between NLR and arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV). METHODS In this cross-sectional study, we examined the relationship between NLR and baPWV in 512 subjects. RESULTS Compared to the control subjects, NLR and baPWV increased in patients with OP. Partial correlation analysis revealed that there was a significant correlation between NLR and baPWV after adjusting for confounding factors in OP. Multivariate linear regression analysis showed that NLR was a significant factor for increased baPWV in patients with OP (β=0.249, p<0.001). However, there was no association between NLR and baPWV in control subjects. CONCLUSION NLR and baPWV are elevated in OP. Moreover, NLR is independently associated with baPWV. Further studies are warranted to investigate whether anti-inflammatory treatment could improve arterial stiffness in postmenopausal women with OP.

Ire1α in Pomc Neurons is Required for Thermogenesis and Glycemia

Whether neuronal inositol-requiring enzyme 1 (Ire1) is required for the proper regulation of energy balance and glucose homeostasis is unclear. We found that pro-opiomelanocortin (Pomc)–specific deficiency of Ire1α accelerated diet-induced obesity concomitant with a decrease in energy expenditure. This hypometabolic phenotype included deficits in thermogenic responses to diet and cold exposure as well as “beiging” of white adipose tissue. We also demonstrate that loss of Ire1α in Pomc neurons impaired whole-body glucose and insulin tolerance as well as hepatic insulin sensitivity. At the cellular level, deletion of Ire1α in Pomc neurons elevated hypothalamic endoplasmic reticulum (ER) stress and predisposed Pomc neurons to leptin and insulin resistance. Together, the current studies extend and confirm conclusions that Ire1α-Xbp1s and associated molecular targets link ER stress in arcuate Pomc neurons to aspects of normal energy and glucose homeostasis.

Higher platelet distribution width predicts poor prognosis in laryngeal cancer

Background Activated platelets promote cancer progression and metastasis. However, the prognostic value of platelet indices in laryngeal cancer remains poorly understood. The purpose of this study was to investigate the predictive significance of platelet indices in laryngeal cancer. Results Of the 241 patients, high platelet distribution width (PDW) levels were observed in 116 (48.1 %) patients. In the Kaplan-Meier analysis, increased PDW was significantly associated with a poorer overall survival (p < 0.001). In the multivariate Cox model, PDW was an independent prognostic index for overall survival (HR=4.381, 95% CI=2.313-8.298, P < 0.001). Method The retrospective study included 241 consecutive patients with laryngeal cancer between January 2009 and December 2009. The relationships between PDW and clinicopathological characteristics were analyzed. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of PDW. Conclusions Elevated PDW might be a novel prognostic marker in laryngeal cancer.

Elevated mean platelet volume predicts poor prognosis in colorectal cancer

Altered mean platelet volume (MPV) is implicated in several malignancies. However, the clinicopathological significance and prognostic value of MPV in colorectal cancer (CRC) is still elusive. The purpose of this study was to elucidate the predictive significance of MPV in CRC. The retrospective study recruited 509 consecutive CRC patients between January 2009 and December 2009. The relationships between MPV and clinicopathological characteristics were analyzed. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of MPV. Of the 509 CRC patients, high MPV levels were detected in 150 (29.5%) patients. Elevated MPV was associated with tumor differentiation (p < 0.001). Patients with increased MPV had poor overall survival compared with those with normal level (60.0% vs. 83.6%, log-rank test, p = 0.035). Cox regression analysis showed that MPV was an independent prognostic factor in CRC (HR = 1.452, 95% CI = 1.118–1.884, p = 0.005). In conclusion, MPV is easily available in routine blood test. Elevated MPV might act as a marker of prognosis and therapeutic target for CRC.

Platelet distribution width correlates with prognosis of non-small cell lung cancer

Platelets play a multifaceted role in cancer progression and metastasis. Mean platelet volume (MPV) and platelet distribution width (PDW) are commonly used platelet parameters from routine blood test. The aim of the present study was to investigate the correlation between platelet indices and prognosis in patients with non-small cell lung cancer (NSCLC). A total of 270 patients who were diagnosed with NSCLC between January 2009 and December 2009 were retrospectively analyzed. Patients’ characteristics and hematologic tests data at initial diagnosis were collected. The overall survival rate was estimated using Kaplan-Meier method. The prognostic analysis was carried out with univariate and multivariate Cox regressions model. Reduced PDW was significantly correlated with T stage, N stage, TNM stage, and histological type of the disease. Moreover, survival analysis showed that the overall survival of patients with PDW ≥ 16.3% was significantly longer than that of those with PDW < 16.3% (P < 0.001). In multivariate Cox regression model, age, sex, TNM stage, and PDW were identified as independent prognostic factors for overall survival (for PDW, P < 0.001). In conclusion, reduced PDW is an unfavorable predictive factor of NSCLC patient survival. Further studies are warranted.

Platelet distribution width correlates with prognosis of gastric cancer

Background Activated platelets promote tumor cell growth, aberrant angiogenesis, and invasion. However, the value of platelet indices for predicting survival in gastric cancer remains unknown. The goal of this study was to investigate the predictive significance of platelet indices in gastric cancer. Result Reduced platelet distribution width (PDW) was significantly correlated with age, carcinoembryonic antigen, tumor stage, nodule stage, and tumor-nodule-metastases stage. Moreover, decreased PDW correlated with a shorter overall survival in gastric cancer. Multivariate analysis identified PDW as an independent prognostic factor for overall survival (hazard ratio: 0.493, 95% confidence interval: 0.319-0.761, p = 0.001). Method A total of 294 patients with gastric cancer were retrospectively analyzed between January 2009 and December 2009. The association between platelet indices and overall survival were evaluated. The prognostic analysis was carried out with Cox regression model. Conclusion PDW is easily available with routine blood counts. Our data revealed that reduced PDW is unfavorable prognostic factor in gastric cancer. Further studies are warranted.