logging in or signing up Molecular Models of Metabolic Syndrome abbmdfacc Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 1921 Category: Science & Tech.. License: All Rights Reserved Like it (11) Dislike it (0) Added: July 21, 2009 This Presentation is Public Favorites: 1 Presentation Description No description available. Comments Posting comment... By: micprr4 (11 month(s) ago) Could you make your presentation available for me. I am pursuing Doctoral reasarch on Metabolic Syndrome and need some informative slides to present at lectures at my clinal site, church and school. Thank You; Michael Parrinello DNP student Saving..... Post Reply Close Saving..... Edit Comment Close By: hikmat1623 (14 month(s) ago) Can to send my email addrress this slide ? Saving..... Post Reply Close Saving..... Edit Comment Close By: hikmat1623 (14 month(s) ago) I think this PPT is realy good,, so I can learn something heaven in adiposite. And Obesity is danger dosorder,, common to fight them.. Saving..... Post Reply Close Saving..... Edit Comment Close By: larapopo (19 month(s) ago) I am working on metabolic syndrome.I found this presentation to be fantastic but is unable to be downloaded.Please can I get help.thanks Popoola Omolara Nigeria. Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Normal Glucose Homeostasis : Normal Glucose Homeostasis Features of The Metabolic Syndrome : Features of The Metabolic Syndrome Nutritionally induced IR develops as metabolic adaptation to circulating FFAs (from intra-abdominal fat stores). circulating FFAs force liver, muscle & other tissues to shift towards storage & oxidation of fats for their energy production. Compensated by a capacity of these tissues to absorb, store & metabolize glucose. Adipose tissue releases TNFα, adiponectin, leptin, and resistin. IR caused by 1) in cellular insulin-receptor levels; 2) responsiveness of intracellular transduction pathways. blood glucose 2ndary to IR is compensated by pancreatic insulin secretion. The Metabolic Syndrome: Pathophysiology : The Metabolic Syndrome: Pathophysiology Local, Portal, & Systemic Effects of Inflammation in Insulin Resistance & ASCVD : Local, Portal, & Systemic Effects of Inflammation in Insulin Resistance & ASCVD Convergence of Macrophage & Adipocyte Functions in Obesity & the Metabolic Syndrome : Convergence of Macrophage & Adipocyte Functions in Obesity & the Metabolic Syndrome Nature Medicine 10, 126 - 127 (2004) The Metabolic Syndrome: Adipocytes as Endocrine Cells : The Metabolic Syndrome: Adipocytes as Endocrine Cells Leptin & Adiponectin as Mediators in the Adipovascular Axis : Leptin & Adiponectin as Mediators in the Adipovascular Axis Obese Adipose Tissue is Characterized by Inflammation & Infiltration by Macrophages : Obese Adipose Tissue is Characterized by Inflammation & Infiltration by Macrophages The Origins of Brown Adipose Tissue : The Origins of Brown Adipose Tissue Enerbäck S. NEJM. 360;19Volume 360:2021-2023 May 7, 2009 Number 19; 2022-2023. Molecular Determinants Involved in White Versus Brown Adipocyte Differentiation : Molecular Determinants Involved in White Versus Brown Adipocyte Differentiation Biochem J. 2006 September 1; 398(Pt 2): 153–168. 4 Elements of the ARN in the Hypothalamus : 4 Elements of the ARN in the Hypothalamus S. P. Kalra: Neuron. 19:227–230, 1997. the orexigenic & anorexigenic signal-producing networks are the 2 basic elements of the circuitry Hypothalamic Sites Associated With Appetite-Regulating Signal Pathways : Hypothalamic Sites Associated With Appetite-Regulating Signal Pathways Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev. 1999 Feb;20(1):68-100. Sagittal section near midline of the rat brain Hypothesized Adiposity Signaling Pathways in the Brain : Hypothesized Adiposity Signaling Pathways in the Brain Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev. 1999 Feb;20(1):68-100. Sagittal section near midline of the brain Insulin and Leptin Increase Expression of POMC and Decrease Expression of AgRP : Insulin and Leptin Increase Expression of POMC and Decrease Expression of AgRP J Clin Invest. 2006 July 3; 116(7): 1761–1766. Adiposity signals (leptin and insulin) inhibit (−) and stimulate (+) NPY/AGRP and αMSH /CART neurons, respectively, in the arcuate nucleus (ARC) Generation of PIP3 Leads to KATP Channel Opening and Consecutive Cell Hyperpolarization : Generation of PIP3 Leads to KATP Channel Opening and Consecutive Cell Hyperpolarization J Clin Invest. 2006 July 3; 116(7): 1761–1766. Potential Effect of Genes and Environment on Adiposity : Potential Effect of Genes and Environment on Adiposity International Journal of Obesity (2008) 32, S109–S119 On the left is presented the 'traditional' environment in which food was rather scarce and energy expenditure was high, mostly related to occupational physical activity. On the right, the more recent modern 'social' and 'built' environment leads to obesogenic behaviors with plenty of cheap high-calorie density food and little need for physical activity. Major Components of Body Weight Regulation in an Obesogenic Environment : Major Components of Body Weight Regulation in an Obesogenic Environment International Journal of Obesity (2008) 32, S109–S119 Changes in the environment of subsequent generations that influence genetic and epigenetic propensity for weight gain. Current habitual lifestyle that promotes sedentary behaviors and provides an oversupply of energy dense foods. Major Components of Body Weight Regulation in an Obesogenic Environment : Major Components of Body Weight Regulation in an Obesogenic Environment International Journal of Obesity (2008) 32, S109–S119 Monozygotic twins reared apart indicate that approximately 33% of the variability in body mass index (BMI) is attributable to nongenetic factors and 67% to genetic factors. Leptin and the Regulation of Adipose Tissue Mass : Leptin and the Regulation of Adipose Tissue Mass Nature. 404, 632-634 (6 April 2000) The cloning of the ob gene and the characterization of leptin has indicated that body fat content is under homeostatic control. The available data suggest that leptin is the afferent signal in a feedback loop regulating adipose tissue mass. Leptin Receptor Expression inthe Arcuate Nucleus of the Hypothalamus : Leptin Receptor Expression inthe Arcuate Nucleus of the Hypothalamus Nature. 404, 632-634 (6 April 2000) In arcuate nucleus of hypothalamus, leptin receptor is expressed in 2 different classes of neurons. 1 class expresses NPY and AGRP; 2 neuropeptides that food intake. Another class expresses POMC, the precursor of -MSH, and CART. Role of Adiponectin in Hypertension : Role of Adiponectin in Hypertension Wang ZV, Scherer PE. Adiponectin, cardiovascular function, and hypertension. Hypertension. 2008 Jan;51(1):8-14. Altered Secretory Profile Associated with Terminal Fat Cell Differentiation : Altered Secretory Profile Associated with Terminal Fat Cell Differentiation (Hypothesis) Adiponectin in Metabolic Versus Autoimmune/Chronic Inflammatory Disease : Adiponectin in Metabolic Versus Autoimmune/Chronic Inflammatory Disease Adiponectin and inflammation: Consensus and controversy. Journal of Allergy and Clinical Immunology - Volume 121, Issue 2 (February 2008) Adiponectin as a Molecular Regulator of Atherosclerosis : Adiponectin as a Molecular Regulator of Atherosclerosis Szmitko PE, Teoh H, Stewart DJ, Verma S. Adiponectin and cardiovascular disease: state of the art? Am J Physiol Heart Circ Physiol. 2007 Apr;292(4):H1655-63. Main Effects Exerted by the More Relevant Adipokines at the Cardiovascular Level : Main Effects Exerted by the More Relevant Adipokines at the Cardiovascular Level Trends in Cardiovascular Medicine. Volume 17, Issue 8, November 2007, Pages 275-283 Crosstalk Between Adipocytes and Macrophages in Obese Adipose Tissue : Crosstalk Between Adipocytes and Macrophages in Obese Adipose Tissue (Hypothesis) Hypothetical Model of Chronic Inflammation and Adipocyte Insulin Resistance : Hypothetical Model of Chronic Inflammation and Adipocyte Insulin Resistance Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112:12 Insulin: 2 Potential Insulin Receptor-Dependent Signal Transduction Pathways : Insulin: 2 Potential Insulin Receptor-Dependent Signal Transduction Pathways Natural History of Insulin Resistance and Type 2 Diabetes : Natural History of Insulin Resistance and Type 2 Diabetes Hormonal and Cellular Mechanisms of Atherosclerosis within the Vessel Wall : Hormonal and Cellular Mechanisms of Atherosclerosis within the Vessel Wall Slide 31: Development of Type 2 Diabetes: Metabolic Pathways in the Liver Slide 32: Pentose Phosphate Pathway Glycolysis Gluconeogenesis - Development of Type 2 Diabetes: Metabolic Pathways in the Liver Slide 33: Insulin-independent glucose uptake Glucagon Insulin Glucose FFA Leptin Insulin-independent glucose uptake Insulin Skeletal muscle Fat Adiponecin TNF- Non-glucose secretagogues Plasma glucose Insulin Signaling in Cells : Insulin Signaling in Cells J. Clin. Invest. 116:1756-1760 (2006). Evolving View of the Biological Functions of the Adipocyte : Evolving View of the Biological Functions of the Adipocyte Leptin and Regulation of Glucose Homeostasis : Leptin and Regulation of Glucose Homeostasis Leptin as an Adipocytokine That Regulates Food Intake and Energy Expenditure : Leptin as an Adipocytokine That Regulates Food Intake and Energy Expenditure Energy Homeostasis and Balance Between Caloric Intake and Energy Expenditure : Energy Homeostasis and Balance Between Caloric Intake and Energy Expenditure Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006 Dec 14;444(7121):847-53. Adipocytes Regulate Energy Balance by Endocrine and Nonendocrine Mechanisms : Adipocytes Regulate Energy Balance by Endocrine and Nonendocrine Mechanisms Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006 Dec 14;444(7121):847-53. Glucose Homeostasis Requires the Coordinated Actions of Various Organs : Glucose Homeostasis Requires the Coordinated Actions of Various Organs Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006 Dec 14;444(7121):847-53. Adipocytes Secrete Proteins with Varied Effects on Glucose Homeostasis : Adipocytes Secrete Proteins with Varied Effects on Glucose Homeostasis Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006 Dec 14;444(7121):847-53. Adipocyte Derived Nonesterified FFA’s Effects on Glucose Homeostasis : Adipocyte Derived Nonesterified FFA’s Effects on Glucose Homeostasis Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006 Dec 14;444(7121):847-53. Peripheral Signaling and Ongoing Energy Balance and Metabolic Homeostasis : Peripheral Signaling and Ongoing Energy Balance and Metabolic Homeostasis Castañeda TR, et al. Obesity and the neuroendocrine control of energy homeostasis: the role of spontaneous locomotor activity. J Nutr. 2005 May;135(5):1314-9. Antiobesity Drug Targets of the GI/CNS and Neurotransmitter/Neuronal Pathways : Antiobesity Drug Targets of the GI/CNS and Neurotransmitter/Neuronal Pathways Obesity Research (2004) 12, 1197–1211 Antiobesity Drug Targets of the Leptin/Insulin/CNS Pathways : Antiobesity Drug Targets of the Leptin/Insulin/CNS Pathways Obesity Research (2004) 12, 1197–1211 Examples of Antiobesity Agents in Development : Examples of Antiobesity Agents in Development CNS agents that affect neurotransmitters or neural ion channels Antidepressants (bupropion) Noradrenaline reuptake inhibitors (GW320659) Selective 5HT 2c receptor agonists Antiseizure agents (topiramate, zonisamide) Some dopamine antagonists CB-1 receptor antagonists (rimonabant) Leptin/insulin/CNS pathway agents Leptin analogues Leptin transport and/or receptor promoters CNTF (Axokine) NPY antagonists AgRP antagonists POMC promoters CART promoters MSH analogues MC4 receptor agonists Obesity Research (2004) 12, 1197–1211 Examples of Antiobesity Agents in Development : Examples of Antiobesity Agents in Development Agents that affect insulin metabolism/activity [PTP-1B inhibitors, PPAR receptor antagonists, short-acting bromocriptine (ergoset), somatostatin agonists (octreotide), and adiponectin/Acrp30 (Famoxin or Fatty Acid Metabolic OXidation INducer)] Gastrointestinal-neural pathway agents Agents that increase CCK and PYY activity Agents that increase GLP-1 activity (extendin 4, liraglutide, DPP IV inhibitor) Agents that decrease ghrelin activity Amylin (pramlinitide) Agents that may increase RMR "Selective" -3 stimulators/agonist UCP homologues Thyroid receptor agonists Obesity Research (2004) 12, 1197–1211 Examples of Antiobesity Agents in Development : Examples of Antiobesity Agents in Development Other agents MCH antagonists Phytostanol analogues Functional oils P57 Amylase inhibitors Growth hormone fragments Synthetic analogues of DHEAS (fluasterone) Antagonists of adipocyte 11B-hydroxysteroid dehydrogenase type 1 activity CRH agonists Carboxypeptidase inhibitors Inhibitors of fatty acid synthesis (cerulenin and C75) Indanones/indanols Aminosterols (Trodusquemine/trodulamine) Other gastrointestinal lipase inhibitors (ATL962) Obesity Research (2004) 12, 1197–1211 Photomicrograph of a Macrophage Foam Cell Isolated From a Hypercholesterolemic Mouse : Photomicrograph of a Macrophage Foam Cell Isolated From a Hypercholesterolemic Mouse Macrophage Itinerary in Adipose Tissue Infiltration : Macrophage Itinerary in Adipose Tissue Infiltration Integration of Metabolic & Immune Responses in Adipocytes & Macrophages : Integration of Metabolic & Immune Responses in Adipocytes & Macrophages Nutrient and Pathogen Sensing or Response Systems: Important Overlapping Features : Nutrient and Pathogen Sensing or Response Systems: Important Overlapping Features Overlapping Metabolic & Inflammatory Pathways in Adipocytes or Macrophages : Overlapping Metabolic & Inflammatory Pathways in Adipocytes or Macrophages Potential Cellular Mechanisms for Activating Inflammatory Signaling : Potential Cellular Mechanisms for Activating Inflammatory Signaling Potential Mechanisms for Activation of Inflammation in Adipose Tissue : Potential Mechanisms for Activation of Inflammation in Adipose Tissue Potential Mechanisms for Adiposity-induced Inflammation in the Liver : Potential Mechanisms for Adiposity-induced Inflammation in the Liver Adipocytes as Endocrine Cells: Adipose Tissue-derived Proteins : Adipocytes as Endocrine Cells: Adipose Tissue-derived Proteins Chronic Exposure to High-fat Diet Induces Leptin Resistance in CNS : Chronic Exposure to High-fat Diet Induces Leptin Resistance in CNS Major Disease Areas Affected by Adipocyte-derived Factors : Major Disease Areas Affected by Adipocyte-derived Factors Major Organ Systems Affected by Adipocyte-derived Factors : Major Organ Systems Affected by Adipocyte-derived Factors Involvement of Adiponectin in Pathological Sequelae of Various Diseases : Involvement of Adiponectin in Pathological Sequelae of Various Diseases Major Extracellular Targets Derived From the Adipocyte Currently Under Study : Major Extracellular Targets Derived From the Adipocyte Currently Under Study Stress and The Metabolic Syndrome : Stress and The Metabolic Syndrome Interactions Between Stress & Immune System : Interactions Between Stress & Immune System The Effects of Stress on GI Function : The Effects of Stress on GI Function Stress and The Metabolic Syndrome : Stress and The Metabolic Syndrome Stress and The Metabolic Syndrome : Stress and The Metabolic Syndrome Stress and The Metabolic Syndrome : Stress and The Metabolic Syndrome Hormonal and Cellular Mechanisms of Atherosclerosis within the Vessel Wall : Hormonal and Cellular Mechanisms of Atherosclerosis within the Vessel Wall Slide 70: Copyright ©2006 American Heart Association Waxman, S. et al. Circulation 2006;114:2390-2411 Culprit and Suspected Vulnerable Atherosclerotic Lesions Mechanisms Relating Adiposity to Cancer Risk : Mechanisms Relating Adiposity to Cancer Risk Effects of Obesity on Hormone Production : Effects of Obesity on Hormone Production Obesity, Hormones and Endometrial Cancer : Obesity, Hormones and Endometrial Cancer You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.
Molecular Models of Metabolic Syndrome abbmdfacc Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 1921 Category: Science & Tech.. License: All Rights Reserved Like it (11) Dislike it (0) Added: July 21, 2009 This Presentation is Public Favorites: 1 Presentation Description No description available. Comments Posting comment... By: micprr4 (11 month(s) ago) Could you make your presentation available for me. I am pursuing Doctoral reasarch on Metabolic Syndrome and need some informative slides to present at lectures at my clinal site, church and school. Thank You; Michael Parrinello DNP student Saving..... Post Reply Close Saving..... Edit Comment Close By: hikmat1623 (14 month(s) ago) Can to send my email addrress this slide ? Saving..... Post Reply Close Saving..... Edit Comment Close By: hikmat1623 (14 month(s) ago) I think this PPT is realy good,, so I can learn something heaven in adiposite. And Obesity is danger dosorder,, common to fight them.. Saving..... Post Reply Close Saving..... Edit Comment Close By: larapopo (19 month(s) ago) I am working on metabolic syndrome.I found this presentation to be fantastic but is unable to be downloaded.Please can I get help.thanks Popoola Omolara Nigeria. Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Normal Glucose Homeostasis : Normal Glucose Homeostasis Features of The Metabolic Syndrome : Features of The Metabolic Syndrome Nutritionally induced IR develops as metabolic adaptation to circulating FFAs (from intra-abdominal fat stores). circulating FFAs force liver, muscle & other tissues to shift towards storage & oxidation of fats for their energy production. Compensated by a capacity of these tissues to absorb, store & metabolize glucose. Adipose tissue releases TNFα, adiponectin, leptin, and resistin. IR caused by 1) in cellular insulin-receptor levels; 2) responsiveness of intracellular transduction pathways. blood glucose 2ndary to IR is compensated by pancreatic insulin secretion. The Metabolic Syndrome: Pathophysiology : The Metabolic Syndrome: Pathophysiology Local, Portal, & Systemic Effects of Inflammation in Insulin Resistance & ASCVD : Local, Portal, & Systemic Effects of Inflammation in Insulin Resistance & ASCVD Convergence of Macrophage & Adipocyte Functions in Obesity & the Metabolic Syndrome : Convergence of Macrophage & Adipocyte Functions in Obesity & the Metabolic Syndrome Nature Medicine 10, 126 - 127 (2004) The Metabolic Syndrome: Adipocytes as Endocrine Cells : The Metabolic Syndrome: Adipocytes as Endocrine Cells Leptin & Adiponectin as Mediators in the Adipovascular Axis : Leptin & Adiponectin as Mediators in the Adipovascular Axis Obese Adipose Tissue is Characterized by Inflammation & Infiltration by Macrophages : Obese Adipose Tissue is Characterized by Inflammation & Infiltration by Macrophages The Origins of Brown Adipose Tissue : The Origins of Brown Adipose Tissue Enerbäck S. NEJM. 360;19Volume 360:2021-2023 May 7, 2009 Number 19; 2022-2023. Molecular Determinants Involved in White Versus Brown Adipocyte Differentiation : Molecular Determinants Involved in White Versus Brown Adipocyte Differentiation Biochem J. 2006 September 1; 398(Pt 2): 153–168. 4 Elements of the ARN in the Hypothalamus : 4 Elements of the ARN in the Hypothalamus S. P. Kalra: Neuron. 19:227–230, 1997. the orexigenic & anorexigenic signal-producing networks are the 2 basic elements of the circuitry Hypothalamic Sites Associated With Appetite-Regulating Signal Pathways : Hypothalamic Sites Associated With Appetite-Regulating Signal Pathways Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev. 1999 Feb;20(1):68-100. Sagittal section near midline of the rat brain Hypothesized Adiposity Signaling Pathways in the Brain : Hypothesized Adiposity Signaling Pathways in the Brain Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev. 1999 Feb;20(1):68-100. Sagittal section near midline of the brain Insulin and Leptin Increase Expression of POMC and Decrease Expression of AgRP : Insulin and Leptin Increase Expression of POMC and Decrease Expression of AgRP J Clin Invest. 2006 July 3; 116(7): 1761–1766. Adiposity signals (leptin and insulin) inhibit (−) and stimulate (+) NPY/AGRP and αMSH /CART neurons, respectively, in the arcuate nucleus (ARC) Generation of PIP3 Leads to KATP Channel Opening and Consecutive Cell Hyperpolarization : Generation of PIP3 Leads to KATP Channel Opening and Consecutive Cell Hyperpolarization J Clin Invest. 2006 July 3; 116(7): 1761–1766. Potential Effect of Genes and Environment on Adiposity : Potential Effect of Genes and Environment on Adiposity International Journal of Obesity (2008) 32, S109–S119 On the left is presented the 'traditional' environment in which food was rather scarce and energy expenditure was high, mostly related to occupational physical activity. On the right, the more recent modern 'social' and 'built' environment leads to obesogenic behaviors with plenty of cheap high-calorie density food and little need for physical activity. Major Components of Body Weight Regulation in an Obesogenic Environment : Major Components of Body Weight Regulation in an Obesogenic Environment International Journal of Obesity (2008) 32, S109–S119 Changes in the environment of subsequent generations that influence genetic and epigenetic propensity for weight gain. Current habitual lifestyle that promotes sedentary behaviors and provides an oversupply of energy dense foods. Major Components of Body Weight Regulation in an Obesogenic Environment : Major Components of Body Weight Regulation in an Obesogenic Environment International Journal of Obesity (2008) 32, S109–S119 Monozygotic twins reared apart indicate that approximately 33% of the variability in body mass index (BMI) is attributable to nongenetic factors and 67% to genetic factors. Leptin and the Regulation of Adipose Tissue Mass : Leptin and the Regulation of Adipose Tissue Mass Nature. 404, 632-634 (6 April 2000) The cloning of the ob gene and the characterization of leptin has indicated that body fat content is under homeostatic control. The available data suggest that leptin is the afferent signal in a feedback loop regulating adipose tissue mass. Leptin Receptor Expression inthe Arcuate Nucleus of the Hypothalamus : Leptin Receptor Expression inthe Arcuate Nucleus of the Hypothalamus Nature. 404, 632-634 (6 April 2000) In arcuate nucleus of hypothalamus, leptin receptor is expressed in 2 different classes of neurons. 1 class expresses NPY and AGRP; 2 neuropeptides that food intake. Another class expresses POMC, the precursor of -MSH, and CART. Role of Adiponectin in Hypertension : Role of Adiponectin in Hypertension Wang ZV, Scherer PE. Adiponectin, cardiovascular function, and hypertension. Hypertension. 2008 Jan;51(1):8-14. Altered Secretory Profile Associated with Terminal Fat Cell Differentiation : Altered Secretory Profile Associated with Terminal Fat Cell Differentiation (Hypothesis) Adiponectin in Metabolic Versus Autoimmune/Chronic Inflammatory Disease : Adiponectin in Metabolic Versus Autoimmune/Chronic Inflammatory Disease Adiponectin and inflammation: Consensus and controversy. Journal of Allergy and Clinical Immunology - Volume 121, Issue 2 (February 2008) Adiponectin as a Molecular Regulator of Atherosclerosis : Adiponectin as a Molecular Regulator of Atherosclerosis Szmitko PE, Teoh H, Stewart DJ, Verma S. Adiponectin and cardiovascular disease: state of the art? Am J Physiol Heart Circ Physiol. 2007 Apr;292(4):H1655-63. Main Effects Exerted by the More Relevant Adipokines at the Cardiovascular Level : Main Effects Exerted by the More Relevant Adipokines at the Cardiovascular Level Trends in Cardiovascular Medicine. Volume 17, Issue 8, November 2007, Pages 275-283 Crosstalk Between Adipocytes and Macrophages in Obese Adipose Tissue : Crosstalk Between Adipocytes and Macrophages in Obese Adipose Tissue (Hypothesis) Hypothetical Model of Chronic Inflammation and Adipocyte Insulin Resistance : Hypothetical Model of Chronic Inflammation and Adipocyte Insulin Resistance Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112:12 Insulin: 2 Potential Insulin Receptor-Dependent Signal Transduction Pathways : Insulin: 2 Potential Insulin Receptor-Dependent Signal Transduction Pathways Natural History of Insulin Resistance and Type 2 Diabetes : Natural History of Insulin Resistance and Type 2 Diabetes Hormonal and Cellular Mechanisms of Atherosclerosis within the Vessel Wall : Hormonal and Cellular Mechanisms of Atherosclerosis within the Vessel Wall Slide 31: Development of Type 2 Diabetes: Metabolic Pathways in the Liver Slide 32: Pentose Phosphate Pathway Glycolysis Gluconeogenesis - Development of Type 2 Diabetes: Metabolic Pathways in the Liver Slide 33: Insulin-independent glucose uptake Glucagon Insulin Glucose FFA Leptin Insulin-independent glucose uptake Insulin Skeletal muscle Fat Adiponecin TNF- Non-glucose secretagogues Plasma glucose Insulin Signaling in Cells : Insulin Signaling in Cells J. Clin. Invest. 116:1756-1760 (2006). Evolving View of the Biological Functions of the Adipocyte : Evolving View of the Biological Functions of the Adipocyte Leptin and Regulation of Glucose Homeostasis : Leptin and Regulation of Glucose Homeostasis Leptin as an Adipocytokine That Regulates Food Intake and Energy Expenditure : Leptin as an Adipocytokine That Regulates Food Intake and Energy Expenditure Energy Homeostasis and Balance Between Caloric Intake and Energy Expenditure : Energy Homeostasis and Balance Between Caloric Intake and Energy Expenditure Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006 Dec 14;444(7121):847-53. Adipocytes Regulate Energy Balance by Endocrine and Nonendocrine Mechanisms : Adipocytes Regulate Energy Balance by Endocrine and Nonendocrine Mechanisms Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006 Dec 14;444(7121):847-53. Glucose Homeostasis Requires the Coordinated Actions of Various Organs : Glucose Homeostasis Requires the Coordinated Actions of Various Organs Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006 Dec 14;444(7121):847-53. Adipocytes Secrete Proteins with Varied Effects on Glucose Homeostasis : Adipocytes Secrete Proteins with Varied Effects on Glucose Homeostasis Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006 Dec 14;444(7121):847-53. Adipocyte Derived Nonesterified FFA’s Effects on Glucose Homeostasis : Adipocyte Derived Nonesterified FFA’s Effects on Glucose Homeostasis Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006 Dec 14;444(7121):847-53. Peripheral Signaling and Ongoing Energy Balance and Metabolic Homeostasis : Peripheral Signaling and Ongoing Energy Balance and Metabolic Homeostasis Castañeda TR, et al. Obesity and the neuroendocrine control of energy homeostasis: the role of spontaneous locomotor activity. J Nutr. 2005 May;135(5):1314-9. Antiobesity Drug Targets of the GI/CNS and Neurotransmitter/Neuronal Pathways : Antiobesity Drug Targets of the GI/CNS and Neurotransmitter/Neuronal Pathways Obesity Research (2004) 12, 1197–1211 Antiobesity Drug Targets of the Leptin/Insulin/CNS Pathways : Antiobesity Drug Targets of the Leptin/Insulin/CNS Pathways Obesity Research (2004) 12, 1197–1211 Examples of Antiobesity Agents in Development : Examples of Antiobesity Agents in Development CNS agents that affect neurotransmitters or neural ion channels Antidepressants (bupropion) Noradrenaline reuptake inhibitors (GW320659) Selective 5HT 2c receptor agonists Antiseizure agents (topiramate, zonisamide) Some dopamine antagonists CB-1 receptor antagonists (rimonabant) Leptin/insulin/CNS pathway agents Leptin analogues Leptin transport and/or receptor promoters CNTF (Axokine) NPY antagonists AgRP antagonists POMC promoters CART promoters MSH analogues MC4 receptor agonists Obesity Research (2004) 12, 1197–1211 Examples of Antiobesity Agents in Development : Examples of Antiobesity Agents in Development Agents that affect insulin metabolism/activity [PTP-1B inhibitors, PPAR receptor antagonists, short-acting bromocriptine (ergoset), somatostatin agonists (octreotide), and adiponectin/Acrp30 (Famoxin or Fatty Acid Metabolic OXidation INducer)] Gastrointestinal-neural pathway agents Agents that increase CCK and PYY activity Agents that increase GLP-1 activity (extendin 4, liraglutide, DPP IV inhibitor) Agents that decrease ghrelin activity Amylin (pramlinitide) Agents that may increase RMR "Selective" -3 stimulators/agonist UCP homologues Thyroid receptor agonists Obesity Research (2004) 12, 1197–1211 Examples of Antiobesity Agents in Development : Examples of Antiobesity Agents in Development Other agents MCH antagonists Phytostanol analogues Functional oils P57 Amylase inhibitors Growth hormone fragments Synthetic analogues of DHEAS (fluasterone) Antagonists of adipocyte 11B-hydroxysteroid dehydrogenase type 1 activity CRH agonists Carboxypeptidase inhibitors Inhibitors of fatty acid synthesis (cerulenin and C75) Indanones/indanols Aminosterols (Trodusquemine/trodulamine) Other gastrointestinal lipase inhibitors (ATL962) Obesity Research (2004) 12, 1197–1211 Photomicrograph of a Macrophage Foam Cell Isolated From a Hypercholesterolemic Mouse : Photomicrograph of a Macrophage Foam Cell Isolated From a Hypercholesterolemic Mouse Macrophage Itinerary in Adipose Tissue Infiltration : Macrophage Itinerary in Adipose Tissue Infiltration Integration of Metabolic & Immune Responses in Adipocytes & Macrophages : Integration of Metabolic & Immune Responses in Adipocytes & Macrophages Nutrient and Pathogen Sensing or Response Systems: Important Overlapping Features : Nutrient and Pathogen Sensing or Response Systems: Important Overlapping Features Overlapping Metabolic & Inflammatory Pathways in Adipocytes or Macrophages : Overlapping Metabolic & Inflammatory Pathways in Adipocytes or Macrophages Potential Cellular Mechanisms for Activating Inflammatory Signaling : Potential Cellular Mechanisms for Activating Inflammatory Signaling Potential Mechanisms for Activation of Inflammation in Adipose Tissue : Potential Mechanisms for Activation of Inflammation in Adipose Tissue Potential Mechanisms for Adiposity-induced Inflammation in the Liver : Potential Mechanisms for Adiposity-induced Inflammation in the Liver Adipocytes as Endocrine Cells: Adipose Tissue-derived Proteins : Adipocytes as Endocrine Cells: Adipose Tissue-derived Proteins Chronic Exposure to High-fat Diet Induces Leptin Resistance in CNS : Chronic Exposure to High-fat Diet Induces Leptin Resistance in CNS Major Disease Areas Affected by Adipocyte-derived Factors : Major Disease Areas Affected by Adipocyte-derived Factors Major Organ Systems Affected by Adipocyte-derived Factors : Major Organ Systems Affected by Adipocyte-derived Factors Involvement of Adiponectin in Pathological Sequelae of Various Diseases : Involvement of Adiponectin in Pathological Sequelae of Various Diseases Major Extracellular Targets Derived From the Adipocyte Currently Under Study : Major Extracellular Targets Derived From the Adipocyte Currently Under Study Stress and The Metabolic Syndrome : Stress and The Metabolic Syndrome Interactions Between Stress & Immune System : Interactions Between Stress & Immune System The Effects of Stress on GI Function : The Effects of Stress on GI Function Stress and The Metabolic Syndrome : Stress and The Metabolic Syndrome Stress and The Metabolic Syndrome : Stress and The Metabolic Syndrome Stress and The Metabolic Syndrome : Stress and The Metabolic Syndrome Hormonal and Cellular Mechanisms of Atherosclerosis within the Vessel Wall : Hormonal and Cellular Mechanisms of Atherosclerosis within the Vessel Wall Slide 70: Copyright ©2006 American Heart Association Waxman, S. et al. Circulation 2006;114:2390-2411 Culprit and Suspected Vulnerable Atherosclerotic Lesions Mechanisms Relating Adiposity to Cancer Risk : Mechanisms Relating Adiposity to Cancer Risk Effects of Obesity on Hormone Production : Effects of Obesity on Hormone Production Obesity, Hormones and Endometrial Cancer : Obesity, Hormones and Endometrial Cancer