, an apical plasma membrane (APM) water channel in salivary glands, lacrimal glands, and airway epithelium, has an important role in fluid secretion. M 3 muscarinic acetylcholine receptor (mAChR)-induced changes in AQP5 localization in rat parotid glands were investigated with immunofluorescence or immunoelectron microscopy, detergent solubility, and gradient density floatation assays. Confocal microscopy revealed AQP5 localization in intracellular vesicles of interlobular duct cells in rat parotid glands and AQP5 trafficking to the APM 10 min after injection of the mAChR agonist cevimeline. Conversely, 60 min after injection, there was a diffuse pattern of AQP5 staining in the cell cytoplasm. The calcium ionophore A-23187 mimicked the effects of cevimeline. Immunoelectron microscopic studies confirmed that cevimeline induced AQP5 trafficking from intracellular structures to APMs in the interlobular duct cells of rat parotid glands. Lipid raft markers flotillin-2 and GM1 colocalized with AQP5 and moved with AQP5 in response to cevimeline. Under control conditions, the majority of AQP5 localized in the Triton X-100-insoluble fraction and floated to the light-density fraction on discontinuous density gradients. After 10-min incubation of parotid tissue slices with cevimeline or A-23187, AQP5 levels decreased in the Triton X-100-insoluble fraction and increased in the Triton X-100-soluble fraction. Thus AQP5 localizes in the intracellular lipid rafts, and M 3 mAChR activation induces AQP5 trafficking to the APM with lipid rafts via intracellular Ca 2ϩ signaling and induces AQP5 dissociation from lipid rafts to nonrafts on the APM in the interlobular duct cells of rat parotid glands.translocation; aquaporin-5 AQUAPORINS (AQPs) form water channels that selectively transport water across the plasma membrane (19). Thirteen mammalian AQPs, AQP0 -AQP12, have been identified (1, 27). AQP5, initially cloned from rat submandibular glands (32), is an apical membrane water channel that is distributed to epithelial cells in several secretory glands, such as salivary glands (10). Salivary fluid secretion is defective in transgenic mice lacking AQP5, indicating that AQP5 has an important role in fluid secretion (24).The parotid glands are innervated by both sympathetic and parasympathetic nerves (2). The activation of M 3 muscarinic acetylcholine receptors (mAChRs) and ␣ 1 -adrenoceptors increases intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) and induces salivary fluid secretion (2). In vitro experiments using rat parotid slices demonstrated that ACh and epinephrine acting at M 3 mAChRs and ␣ 1 -adrenoceptors, respectively, induce a rapid increase in the AQP5 levels in the apical plasma membrane (APM) by increasing [Ca 2ϩ ] i (14, 15). We previously investigated (16) the possible role of Ca 2ϩ -mediated intracellular signal transduction in the M 3 mAChR agonist-induced increase in AQP5 levels in the APM and demonstrated that activation of endogenous nitric oxide synthase and protein kinase G in the cells is coupled with t...

Abstract. Salivary secretion occurs in response to stimulation by neurotransmitters released from autonomic nerve endings. The molecular mechanisms underlying the secretion of water, a main component of saliva, from salivary glands are not known; the plasma membrane is a major barrier to water transport. A 28-kDa integral membrane protein, distributed in highly waterpermeable tissues, was identified as a water channel protein, aquaporin (AQP). Thirteen AQPs (AQP0 -AQP12) have been identified in mammals. AQP5 is localized in lipid rafts under unstimulated conditions and translocates to the apical plasma membrane in rat parotid glands upon stimulation by muscarinic agonists. The importance of increases in intracellular calcium concentration [Ca 2+ ] i and the nitric oxide synthase and protein kinase G signaling pathway in the translocation of AQP5 is reviewed in section I. Signals generated by the activation of Ca 2+ mobilizing receptors simultaneously trigger and regulate exocytosis. Zymogen granule exocytosis occurs under the control of essential process, stimulus-secretion coupling, in salivary glands. Ca 2+ signaling is a principal signal in both protein and water secretion from salivary glands induced by cholinergic stimulation. On the other hand, the cyclic adenosine monophosphate (cAMP)/ cAMP-dependent protein kinase system has a major role in zymogen granule exocytosis without significant increases in [Ca 2+ ] i . In section II, the mechanisms underlying the control of salivary protein secretion and its dysfunction are reviewed.

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Background. This study evaluated the effectiveness of the multidisciplinary team (including a specialist, a dietitian, a physical exercise trainer, a surgeon for bariatric surgery, an acupuncturist, and several health educators) for obesity management and the body composition change and improvements in metabolic biomarkers during a 2-year follow-up. Materials and Methods. A total of 119 patients participated in the multidisciplinary team for obesity. Patients were followed up at 3 months, 6 months, 1 year, 18 months, and 2 years after their first visit. Individuals were divided into the high-protein diet (HPD) and standard-protein diet (SPD) group according to their results on a diet questionnaire that they filled out during follow-up. Results. After 1.2 years, the mean body weight of the participants dropped from 89.7 kg to 80.9 kg ( p < 0.001 ). The body adiposity index was reduced from 33.9 to 32.0 ( p < 0.001 ), while the fat-free mass index from 17.0 to 15.2 ( p = 0.043 ). Fasting glucose and HbA1c were also lower after treatment ( p = 0.002 and 0.038 for FPG and HbA1c, respectively). Fasting insulin and HOMA-IR were reduced ( p = 0.002 and <0.001 for fasting insulin and HOMA-IR, respectively). HDL-c increased along with weight loss (1.06 mmol/L vs. 1.19 mmol/L, p < 0.001 ), and transaminase levels significantly dropped ( p = 0.001 and 0.021 for ALT and AST, respectively). During treatment, mean protein intake was 29.9% in the HPD group and 19.5% in the SPD group ( p < 0.001 ). Weight loss, reduction of visceral fat area, maintenance of lean body mass, body adiposity index, and fat-free mass index showed no statistical significance between the HPD and SPD groups, as well as glucose metabolic variables. Conclusions. A multidisciplinary team for obesity management could significantly reduce body weight and improve metabolic indicators, including HDL-c, transaminase, and insulin resistance. A high-protein diet does not produce better weight control or body composition compared with a standard calorie-restricted diet.

Introduction. The interactions of central obesity and body composition with thyroid hormones and the hypothalamus-pituitary-adrenal (HPA) axis are unclear; both central obesity and body composition have an impact on energy homeostasis. Our study aimed to investigate the association between body composition and pituitary hormones, including the HPA axis and pituitary-thyroid axis, in a Chinese population of euthyroid overweight and obese individuals. Methods. This was a cross-sectional study. Overweight and obese patients who regularly visited the multidisciplinary team (MDT) for obesity at Peking University First Hospital were enrolled in the study. Thyroid function, morning serum ACTH and cortisol levels, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), body composition, and metabolic indicators, including liver function and the lipid profile, were measured at the first visit. Statistical analysis was performed using SPSS version 21.0 (IBM, USA). Results. In total, 441 patients with overweight or obesity were enrolled (male/female, 123/318). Patients were assigned to four groups according to the thyroid-stimulating hormone (TSH) level stratified by quartiles, and increased body mass index (BMI) was revealed in the highest TSH quartile group ( p = 0.002 ). Hip circumference (HC) of patients in the highest TSH quartile group was significantly increased ( p = 0.021 ). Morning ACTH levels and fasting insulin levels were significantly elevated in patients in the highest TSH quartile group ( p = 0.027 for fasting insulin, p < 0.001 for ACTH). In the female subgroup, patients in the highest TSH quartile group showed increases in BMI ( p = 0.010 ), waist circumference (WC) ( p = 0.007 ), muscle mass of the lower extremities ( p = 0.020 ), fasting C-peptide ( p = 0.031 ), and ACTH ( p = 0.002 ). In the male subgroup, patients in the highest TSH quartile group exhibited higher BMI ( p = 0.017 ), HC ( p = 0.036 ), and ACTH ( p = 0.003 ). Among patients in the highest ACTH quartile group, there was an elevated proportion of males ( p = 0.003 ), and FT3 ( p = 0.005 ), fasting insulin ( p = 0.037 ), and cortisol ( p < 0.001 ) levels were increased. Weight ( p < 0.001 ), BMI ( p < 0.001 ), WC ( p < 0.001 ), HC ( p < 0.001 ), muscle mass of the upper extremities ( p = 0.003 ), muscle mass of the lower extremities ( p = 0.005 ), and total muscle mass ( p = 0.003 ) were elevated in patients in the highest ACTH quartile group. HC was found to be an independent factor after adjustment for other confounders and was positively associated with the TSH level ( p = 0.004 for the regression model, B = 0.152, p = 0.004 ). Conclusions. BMI is positively correlated with TSH and ACTH levels in both male and female obese individuals. The ACTH level was positively associated with male sex and increased BMI and muscle mass. Hip circumference was an independent factor that was positively related to TSH levels.