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Lung inflammation is modulated by cholinergic signaling and exercise training protects mice against pulmonary emphysema development; however, whether exercise training engages cholinergic signaling is unknown.As cholinergic signaling is directly linked to the vesicular acetylcholine transporter (VAChT) levels, we evaluated whether the effects of aerobic exercise training depend on the VAChT levels in mice with pulmonary emphysema.Wild-type (WT) and mutant (KDCigarette smoke reduced body mass in mice (p 0.001) and increased alveolar diameter (p 0.001), inflammation (p 0.001) and collagen deposition (p 0.01) in lung tissue. Both trained groups improved their performance in the final physical test compared to the initial test (p 0.001). In WT mice, exercise training protected against emphysema development (p 0.05), reduced mononuclear cells infiltrate (p 0.001) and increased MAC-2 positive cells in lung parenchyma (p 0.05); however, these effects were not observed in KDOur data suggest that the protective effects of aerobic exercise training on pulmonary emphysema are, at least in part, dependent on the integrity of the lung cholinergic signaling.

Physiology teaching resources have advanced to include innovative pedagogical approaches that meet the learning expectations of the current generation of students, while at the same time ensuring content delivery is accurate and the use of technologies is appropriate. We developed a quick experimental assay protocol to introduce the basic concepts of cardiac rhythms, and to demonstrate simultaneously that smartphone applications are a reliable and cost-effective tool for data collection in teaching the scientific method and performing physiology activities. The cardiac rhythm dance (CRD) protocol engages students in dancing a cardiac cyclelike movement to the rhythm of classical, pop, and samba music, and measuring their own cardiac frequency. Students collected their own data using the app Instant Heart Rate (Azumio). The CRD protocol allowed students to conclude that cardiac cycle-like movements paced by a pop song could represent the normal cardiac rhythm, whereas a classical song induced a significant reduction of heart rate, and the samba song significantly increased heart rate compared with the pop song. After group discussion, students considered that the pop rhythm is more realistic of day-by-day movement rhythms and is equivalent to the steady state of daily cardiac rhythms. Students considered the bradycardic and tachycardic movements to the dancing performed to the classical and samba rhythms, respectively. Thus the CRD protocol provides a multiple sensory-based and active learning resource that can engage students in learning cardiovascular physiology and recognizes smartphones as scientific instruments for collecting data during hands-on activities.

The effect of fish oil (FO) treatment on high‐fat (HF) diet‐induced obesity and metabolic syndrome was addressed by analyzing dysfunctions in cells of different adipose depots. For this purpose, mice were initially induced to obesity for 8 weeks following a treatment with FO containing high concentration of EPA compared to DHA (5:1), for additional 8 weeks (by gavage, 3 times per week). Despite the higher fat intake, the HF group showed lower food intake but higher body weight, glucose intolerance and insulin resistance, significant dyslipidemia and increased liver, subcutaneous (inguinal‐ING) and visceral (retroperitoneal‐RP) adipose depots mass, accompanied by adipocyte hypertrophy and decreased cellularity in both adipose tissue depots. FO treatment reversed all these effects, as well as it improved the metabolic activities of isolated adipocytes, such as glucose uptake and lipolysis in both depots, and de novo synthesis of fatty acids in ING adipocytes. HF diet also significantly increased both the pro and anti‐inflammatory cytokines expression by adipocytes, while HF + FO did not differ from control group. Collectively, these data show that the concomitant administration of FO with the HF diet is able to revert metabolic changes triggered by the diet‐induced obesity, as well as to promote beneficial alterations in adipose cell activities. The main mechanism underlying all systemic effects involves direct and differential effects on ING and RP adipocytes., The manuscript show relevant effects of fish oil (FO) treatment reversing both the metabolic syndrome induced by high‐fat diet (HF) and the changes in subcutaneous (inguinal ‐ING) and visceral (retroperitoneal ‐RP) adipocytes, such as glucose uptake, lipolysis, and lipogenesis. The major findings of our study is that the FO treatment reverses the deleterious effects caused by the excessive intake of a HF diet, and the mechanism involves, at least in part, direct and differential effects on ING and RP adipocytes. Altogether, these effects prevented adipocyte hypertrophy caused by HF diet and reflected in decreased adiposity. Additionally, FO treatment decreased the gene and protein expression of inflammation‐related factors. Thus, the work provided important evidence concerning the effectiveness of a low‐cost agent (as the FO) to treat the metabolic and inflammatory disorders triggered by obesity, which causes thousands of deaths annually and burdens the public coffers.

Exacerbated expansion of adipose tissue seen in diet-induced obesity leads to endocrine dysfunction and disturbance in adipokine secretion, with such abnormal profile positively associated with type 2 diabetes and other mild chronic inflammatory conditions. Ginkgo biloba extract (GbE), a mixture of polyphenols with antioxidant properties, has been recently investigated in a variety of experimental models of endocrine dysfunction, with several potentially beneficial effects identified, including improvement in insulin sensitivity in obese rats, and reduction of weight gain in ovariectomy-induced obesity and diet-induced obesity. The aim of this study was to investigate in high fat diet-induced obese male rats the effects of GbE supplementation for two weeks on adipocyte volume and adipose tissue lipid accumulation. GbE supplementation was effective in reducing energy intake in obese rats compared to the saline-treated placebo group. Epididymal adipocyte volume was reduced in GbE-supplemented rats, as were epididymal [1-14C]-acetate incorporation into fatty acids, perilipin (Plin 1) and fatty acid synthase (Fasn) mRNA, and FAS protein levels. Adipocyte hypertrophy in obesity is associated with insulin resistance, and in the present study we observed a reduction in the adipocyte volume of GbE-supplemented obese rats to dimensions equivalent to adipocytes from non-obese rats. GbE supplementation significantly reduced acetate accumulation and tended to reduce [3H]-oleate incorporation, into epididymal adipose tissue, suggesting a potentially anti-obesogenic effect in longer term therapies. Further studies that investigate the effects of GbE supplementation in other experimental models are required to fully elucidate its suggested beneficial effects on mild chronic inflammatory conditions.

This study aimed to investigate the effects of two commercially available fish oils (FOs) containing different proportions of two omega-3 fatty acids (FA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the metabolic and endocrine dysfunctions of white adipose tissue resulting from obesity. Male C57BL/6J mice, 8 weeks old, received a control or high-fat diet (CO and HF groups, with 9% and 59% energy from fat, respectively) for 8 weeks. The next 8 weeks, the HF group was subdivided into HF, HF+FO/E (HF+5:1 EPA:DHA), and HF+FO/D (HF+5:1 DHA:EPA). Supplementation was performed by gavage, three times a week. All groups that received the HF diet had lower food and caloric intake, but a higher fat intake, body weight (BW) gain, glucose intolerance, and a significant increase in inguinal (ING), retroperitoneal (RP), and epididymal (EPI) adipose tissues when compared to the CO group. Additionally, HF and HF+FO/D groups showed insulin resistance, adipocyte hypertrophy, increased lipolysis and secretion of TNF-α, resistin and IL-10 adipokines by ING and RP adipocytes, and adiponectin only by the HF+FO/D group in ING adipocytes. All of these effects were completely reversed in the HF+FO/E group, which also showed partial reversion in BW gain and glucose intolerance. Both the HF+FO/E and HF+FO/D groups showed a reduction in ING and RP adipose depots when compared to the HF group, but only HF+FO/E in the EPI depot. HF+FO/E, but not HF+FO/D, was able to prevent the changes triggered by obesity in TNF-α, Il-10, and resistin secretion in ING and RP depots. These results strongly suggest that different EPA:DHA ratios have different impacts on the adipose tissue metabolism, FO being rich in EPA, but not in DHA, and effective in reversing the changes induced by obesity.

The increasing impact of obesity on global human health intensifies the importance of studies focusing on agents interfering with the metabolism and remodeling not only of the white adipose tissue (WAT) but also of the liver. In the present study, we have addressed the impact of n-3 PUFA in adipose cells’ proliferation and adipogenesis, as well as in the hepatic lipid profile and morphology. Mice were induced to obesity by the consumption of a high-fat diet (HFD) for 16 weeks. At the 9th week, the treatment with fish oil (FO) was initiated and maintained until the end of the period. The FO treatment reduced the animals’ body mass, plasma lipids, glucose, plasma transaminases, liver mass, triacylglycerol, and cholesterol liver content when compared to animals consuming only HFD. FO also decreased the inguinal (ing) WAT mass, reduced adipocyte volume, increased adipose cellularity (hyperplasia), and increased the proliferation of adipose-derived stromal cells (AdSCs) which corroborates the increment in the proliferation of 3T3-L1 pre-adipocytes or AdSCs treated in vitro with n-3 PUFA. After submitting the in vitro treated (n-3 PUFA) cells, 3T3-L1 and AdSCs, to an adipogenic cocktail, there was an increase in the mRNA expression of adipogenic transcriptional factors and other late adipocyte markers, as well as an increase in lipid accumulation when compared to not treated cells. Finally, the expression of browning-related genes was also higher in the n-3 PUFA treated group. We conclude that n-3 PUFA exerts an attenuating effect on body mass, dyslipidemia, and hepatic steatosis induced by HFD. FO treatment led to decreasing adiposity and adipocyte hypertrophy in ingWAT while increasing hyperplasia. Data suggest that FO treatment might induce recruitment (by increased proliferation and differentiation) of new adipocytes (white and/or beige) to the ingWAT, which is fundamental for the healthy expansion of WAT.

Inflammation plays a central role in the development of asthma, which is considered an allergic disease with a classic Th2 inflammatory profile. However, cytokine IL-17 has been examined to better understand the pathophysiology of this disease. Severe asthmatic patients experience frequent exacerbations, leading to infection, and subsequently show altered levels of inflammation that are unlikely to be due to the Th2 immune response alone. This study estimates the effects of anti-IL-17 therapy in the pulmonary parenchyma in a murine asthma model exacerbated by LPS. BALB/c mice were sensitized with intraperitoneal ovalbumin and repeatedly exposed to inhalation with ovalbumin, followed by treatment with or without anti-IL-17. Twenty-four hours prior to the end of the 29-day experimental protocol, the two groups received LPS (0.1 mg/ml -intratracheal OVA-LPS and OVA LPS IL-17). We subsequently evaluated bronchoalveolar lavage fluid (BALF), performed a lung tissue morphometric analysis and measured IL6 gene expression. OVA-LPS-treated animals treated with anti-IL-17 showed decreased pulmonary inflammation, edema, oxidative stress and extracellular matrix remodeling compared to the non-treated OVA and OVA-LPS groups (p < 0.05). The anti-IL-17 treatment also decreased the numbers of dendritic cells, FOXP3, NF-κB and Rho kinase 1- and 2-positive cells compared to the non-treated OVA and OVA-LPS groups (p < 0.05). In conclusion, these data suggest that inhibition of IL-17 is a promising therapeutic avenue, even in exacerbated asthmatic patients, and significantly contributes to the control of Th1/Th2/Th17 inflammation, chemokine expression, extracellular matrix remodeling and oxidative stress in a murine experimental asthma model exacerbated by LPS.

FAPESP Background: We have recently demonstrated that palmitoleic acid (16:1n7) increases lipolysis, glucose uptake and glucose utilization for energy production in white adipose cells. In the present study, we tested the hypothesis that palmitoleic acid modulates bioenergetic activity in white adipocytes. Methods: For this, 3 T3-L1 pre-adipocytes were differentiated into mature adipocytes in the presence (or absence) of palmitic (16:0) or palmitoleic (16:1n7) acid at 100 or 200 mu M. The following parameters were evaluated:lipolysis, lipogenesis, fatty acid (FA) oxidation, ATP content, oxygen consumption, mitochondrial mass, citrate synthase activity and protein content of mitochondrial oxidative phosphorylation (OXPHOS) complexes. Results: Treatment with 16:1n7 during 9 days raised basal and isoproterenol-stimulated lipolysis, FA incorporation into triacylglycerol (TAG), FA oxidation, oxygen consumption, protein expression of subunits representing OXPHOS complex II, III, and V and intracellular ATP content. These effects were not observed in adipocytes treated with 16:0. Conclusions: Palmitoleic acid, by concerted action on lipolysis, Gamma A esterification, mitochondrial Gamma A oxidation, oxygen consumption and ATP content, does enhance white adipocyte energy expenditure and may act as local hormone. Univ Fed Sao Paulo, Inst Environm Sci Chem & Pharmaceut, Dept Biol Sci, 210 Sao Nicolau St, BR-09913030 Diadema, Brazil Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo, Brazil Cruzeiro do Sul Univ, Inst Phys Act Sci & Sports, Interdisciplinary Postgrad Program Hlth Sci, Sao Paulo, Brazil Univ Fed Espirito Santo, Hlth Sci Ctr, Dept Nursing, Vitoria, Spain Univ Fed Sao Paulo, Inst Environm Sci Chem & Pharmaceut, Dept Biol Sci, 210 Sao Nicolau St, BR-09913030 Diadema, Brazil FAPESP: 2011/51627-8 FAPESP: 2011/51701-3 Web of Science

Aims: Studies suggest that IL17 modulates inflammatory and infectious responses. Objectives: To evaluate anti-IL17 treatment in an asthma animal model exacerbated by LPS. Methods: we studied hyperresponsiveness, inflammation, NO-arginase and oxidative stress pathways, remodeling, Rho-kinase 1 and 2, arginase 1 and NFKB in airways of 36 BALB/c male mice repeatedly exposed to ovalbumin and treated or not with anti IL17. Twenty-four hours before the end of experimental protocol a group received LPS (5mg/kg). Results: OVA-LPS-antiIL17 showed: decrease in %Ers-Mch(47.3±4.2cmH 2 O/L/s), %Rrs-Mch(36.7±4.2cmH2O/L/s), eosinophils (7.8±0.4) and neutrophils (1.5±0.2)-10 4 cells/mL in BALF, CD4+(3.1±0.3%), CD8+(2.4±0.3), IL2(1.9±0.1), IL4(4.8±0.7), IL5(3.3±0.7), IL6(2.2±0.3), IL10(2.9±0.3), IL13(14.6±0.9), IL17(5.7±0.9), TNFα(6.3±1.3), MMP9(10.8±1.1), MMP12(3.1±0.5), TIMP1(3.8±0.6), TGFβ1(11.3±1.3), TARC (4.7±0.35), iNOS(5.2±0.5), NFκB(3.4±0.5), Rho-kinase 1(7.8±0.3) Rho-kinase 2(17.9±1.3) positive cells/10 4 μm 2 , collagen fibers subtypes I(22.9±0.6%), collagen fibers III(10.2±1.1%), actin(27.6±3.1%), decorin (2.0±0.5%), lumican(15.9±1.1%), biglican(9.4±0.6%), fibronectin(3.5±0.6%), eotaxin(0.3±0.0%), PGF2α(9.5±0.9%) contents, RT-PCR for IL-6(0.7±0.1) and arginase 1(2.95±1.5) mRNA levels(UA) compared to OVA-LPS (p Conclusions: IL17 is involved in the control of hyperresponsiveness, Th1/Th2/Th17 inflammation, chemokine expression, remodeling, NO-arginase and oxidative stress pathways in an asthma model exacerbated by LPS. These effects are associated to NFkb and Rho-kinase 1 activation. Financial Support: FAPESP, CNPq, LIM-20-HC-FMUSP.

Aims: ARDS is a severe cause of respiratory failure without any effective pharmacological treatment available. Objectives: to investigate the mechanisms involved in the effect of anti-IL17 in a model of LPS-induced acute lung injury (ALI). Methods: BALB-c mice were divided into four groups: LPS and LPS-anti-IL17 groups received LPS (5mg/kg-intratracheallly). SAL-anti-IL17 and LPS-anti-IL17 received 1h before LPS administration a single dose of anti-IL17(7.5 μg). We measured: exhaled nitric oxide (eNO); respiratory mechanics (Rrs and Ers); BALF cell counts; cytokine expression, extracellular matrix remodeling, oxidative stress and the genic expression of IL-6, Arginase 1 and VAChT in the lung tissue. Results: LPS-anti-IL17 compared to LPS groups showed: eNO (50.1±4.2vs17.8±2.1ppb), neutrophils (0.01±0.003vs0.002±0.0009)- and macrophages (2.6±0.4vs1.5±0.2)-104μm2/mL in BALF, Rrs (1.24±0.05vs0.62±0.01cmH2O/L/s), Ers (72.2±2.2vs43.84±3.04mL/cmH2O), TNFα(7.7±1.3vs3.9±0.9)-, IL-10 (2.1±0.2vs0.9±0.1)-, IL-13(3.0±0.2vs6.0±0.6)-, IL-17 (7.5±0.6vs4.8±0.5)-, p65-NFκB(2.1±0.4vs0.7±0.1)-, MMP-9 (13.1±0.8vs5.8±0.4)-, TIMP-1 (8.4±0.9vs4.5±0.5)-, iNOS (4.6±0.6vs1.9±0.1)-positive cells/104μm2, collagen fibers (23.9±2.6vs9.6±0.6%), PGF2α (2.12±0.21vs0.19±0.02%) contents and decrease genic expression of IL-6 (3.4±0.9vs0.7±0.2), Arginase-1 (6.5±1.4vs0.9±0.1) and VAChT (13.7±4.3vs6.5±0.8) mRNA levels (UA) compared with LPS group (p Conclusion: Anti-IL17 modulate the early phase of ALI by controlling inflammatory, remodeling and oxidative stress pathways. Anti-inflammatory cholinergic pathway is activated in ALI and anti-IL17 controlled this response. Financial Support: FAPESP, CNPq, LIM-20-HC-FMUSP.

Obesogenic diets increase body weight and cause insulin resistance (IR), however, the association of these changes with the main macronutrient in the diet remains to be elucidated. Male C57BL/6 mice were fed with: control (CD), CD and sweetened condensed milk (HS), high-fat (HF), and HF and condensed milk (HSHF). After 2 months, increased body weight, glucose intolerance, adipocyte size and cholesterol levels were observed. As compared with CD, HS ingested the same amount of calories whereas HF and HSHF ingested less. HS had increased plasma AST activity and liver type I collagen. HF caused mild liver steatosis and hepatocellular damage. HF and HSHF increased LDL-cholesterol, hepatocyte and adipocyte hypertrophy, TNF-α by macrophages and decreased lipogenesis and adiponectin in adipose tissue (AT). HSHF exacerbated these effects, increasing IR, lipolysis, mRNA expression of F4/80 and leptin in AT, Tlr-4 in soleus muscle and IL-6, IL-1β, VCAM-1, and ICAM-1 protein in AT. The three obesogenic diets induced obesity and metabolic dysfunction. HS was more proinflammatory than the HF and induced hepatic fibrosis. The HF was more detrimental in terms of insulin sensitivity, and it caused liver steatosis. The combination HSHF exacerbated the effects of each separately on insulin resistance and AT inflammatory state.

Made available in DSpace on 2018-12-11T16:41:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) White adipose tissue (WAT) plays a fundamental role in maintaining energy balance and important endocrine functions. The loss of WAT modifies adipokine secretion and disrupts homeostasis, potentially leading to severe metabolic effects and a reduced quality of life. Doxorubicin is a chemotherapeutic agent used clinically because of its good effectiveness against various types of cancer. However, doxorubicin has deleterious effects in many healthy tissues, including WAT, liver, and skeletal and cardiac muscles. Our objective was to investigate the effects of doxorubicin on white adipocytes through in vivo and in vitro experiments. Doxorubicin reduced the uptake of glucose by retroperitoneal adipocytes and 3T3-L1 cells via the inhibition of AMP-activated protein kinase Thr172 phosphorylation and glucose transporter 4 content. Doxorubicin also reduced the serum level of adiponectin and, to a greater extent, the expression of genes encoding lipogenic (Fas and Acc) and adipogenic factors (Pparg, C/ebpa, and Srebp1c) in retroperitoneal adipose tissue. In addition, doxorubicin inhibited both lipogenesis and lipolysis and reduced the hormone-sensitive lipase and adipose tissue triacylglycerol lipase protein levels. Therefore, our results demonstrate the impact of doxorubicin on WAT. These results are important to understand some side effects observed in patients receiving chemotherapy and should encourage new adjuvant treatments that aim to inhibit these side effects. Immunometabolism Research Group Department of Cellular Biology and Development Institute of Biomedical Sciences University of São Paulo (USP) Department of Biological Sciences Institute of Environmental Sciences Chemical and Pharmaceutical Federal University of Sao Paulo (UNIFESP) Department of Physiology Physiology of Nutrition Discipline Federal University of São Paulo (UNIFESP) Faculty of Nursing and Nutrition Federal University of Goiás (UFG) Department of Psychobiology Universidade Federal de São Paulo-UNIFESP Department of Physical Education State University of São Paulo Júlio de Mesquita Filho (UNESP) Department of Physical Education State University of São Paulo Júlio de Mesquita Filho (UNESP) FAPESP: 2013/09367-4

Background: Palmitoleic acid was previously shown to improve glucose homeostasis by reducing hepatic glucose production and by enhancing insulin-stimulated glucose uptake in skeletal muscle. Herein we tested the hypothesis that palmitoleic acid positively modulates glucose uptake and metabolism in adipocytes.Methods: for this, both differentiated 3 T3-L1 cells treated with either palmitoleic acid (16: 1n7, 200 mu M) or palmitic acid (16: 0, 200 mu M) for 24 h and primary adipocytes from mice treated with 16: 1n7 (300 mg/kg/day) or oleic acid (18: 1n9, 300 mg/kg/day) by gavage for 10 days were evaluated for glucose uptake, oxidation, conversion to lactate and incorporation into fatty acids and glycerol components of TAG along with the activity and expression of lipogenic enzymes.Results: Treatment of adipocytes with palmitoleic, but not oleic (in vivo) or palmitic (in vitro) acids, increased basal and insulin-stimulated glucose uptake and GLUT4 mRNA levels and protein content. Along with uptake, palmitoleic acid enhanced glucose oxidation (aerobic glycolysis), conversion to lactate (anaerobic glycolysis) and incorporation into glycerol-TAG, but reduced de novo fatty acid synthesis from glucose and acetate and the activity of lipogenic enzymes glucose 6-phosphate dehydrogenase and ATP-citrate lyase. Importantly, palmitoleic acid induction of adipocyte glucose uptake and metabolism were associated with AMPK activation as evidenced by the increased protein content of phospho(p) Thr172AMPKa, but no changes in pSer473Akt and pThr308Akt. Importantly, such increase in GLUT4 content induced by 16: 1n7, was prevented by pharmacological inhibition of AMPK with compound C.Conclusions: in conclusion, palmitoleic acid increases glucose uptake and the GLUT4 content in association with AMPK activation. Univ São Paulo, Inst Biomed Sci, Dept Physiol & Biophys, São Paulo, Brazil Universidade Federal de São Paulo, Inst Environm Sci Chem & Pharmaceut, Dept Biol Sci, BR-09913030 Diadema, Brazil Cruzeiro Univ, Inst Phys Activ Sci & Sports, Program Postgrad Human Movement Sci, São Paulo, Brazil Universidade Federal de São Paulo, Inst Environm Sci Chem & Pharmaceut, Dept Biol Sci, BR-09913030 Diadema, Brazil Web of Science

Doxorubicin is an anthracyclin antibiotic commonly used in chemotherapy against several types of cancer, however it has a great number of side effects [1,2]. Doxorubicin treatment reduces body weight, affects total cholesterol, free fatty acids and the level of fasting blood glucose [3]. Furthermore this chemotherapy can act to damage the adipocytes increasing the development of insulin resistance in peripheral tissues [1]. Our aim was to investigate the doxorubicin effects on adipocyte tissue and its functions.