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Disordered Skeletal Muscle Oxidative Metabolism In Human Obesity and Type 2 Diabetes

Author : Ghadi Antoun
Publisher :
Page : pages
File Size : 37,21 MB
Release : 2016
Category :
ISBN :

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Obesity and type 2 diabetes mellitus (T2DM) are both complex diseases with multifactorial etiologies. Together they affect over 640 million people worldwide and have a significant impact on the global healthcare system incurring costs of over 800 billion dollars. The overall goal of my doctoral research has been to elucidate metabolic predictors and underlying mechanisms in obesity and T2DM. Specifically, I have examined mechanisms contributing to disordered oxidative metabolism in skeletal muscle. My research included participants who were recruited from the Ottawa Hospital Weight Management Clinic in which they completed a clinically supervised meal-replacement and lifestyle intervention program. More so, my doctoral studies evaluated characteristics of muscle mitochondrial function in obesity and T2DM and revealed impaired mitochondrial respiration and electron transport chain supercomplex assembly in muscle from patients with T2DM. The first aim was to study the impact of T2DM on weight loss ability in a large population of obese patients participating in a standardized meal replacement and lifestyle modification program. As there is considerable variability in weight loss propensity, it was found that T2DM significantly deters weight loss although the effect is not large. Since skeletal muscle energetics are central in the development and progression of obesity and T2DM, the second and third aims were to study mitochondrial function in this tissue with the idea of uncovering molecular etiologies. The second aim found deficiencies in mitochondrial respiration in individuals with obesity and T2DM compared to individuals with obesity alone. Reductions in mitochondrial respiration were correlated with increasing levels of HbA1C and attributed to paucity in supercomplex formation in the mitochondrial inner membrane (MIM) of the electron transport chain (ETC). The third aim was to delineate differential fuel oxidation mechanisms and circulating protein biomarkers in obese diet-sensitive (ODS) and obese diet-resistant (ODR) participants following a high fat meal (HFM) challenge. Whole-body analyses were conducted in addition to measures in blood, adipose tissue, skeletal muscle and primary cells. Remarkable increases in oxidative capacity were measured post-HFM. In addition, impaired mitochondrial function was found in the ODR group despite lack of differences in mitochondrial content or the assembly of supercomplexes. Differences were also found in circulating acylcarnitines as well as expression of several proteins including Heat shock 70 kDa protein 1A/1B, Tyrosine-protein kinase Fgr, and Peptidyl-prolyl cis-trans isomerase D. Ultimately, a better understanding of mechanisms involved could lead to significant improvements in personalized medical approaches in obesity and T2DM.

Mitochondria in Obesity and Type 2 Diabetes

Author : Beatrice Morio
Publisher : Academic Press
Page : 460 pages
File Size : 23,48 MB
Release : 2019-04-26
Category : Science
ISBN : 0128117524

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Mitochondria in Obesity and Type 2 Diabetes: Comprehensive Review on Mitochondrial Functioning and Involvement in Metabolic Diseases synthesizes discoveries from laboratories around the world, enhancing our understanding of the involvement of mitochondria in the etiology of diseases, such as obesity and type 2 diabetes. Chapters illustrate and provide an overview of key concepts on topics such as the role of mitochondria in adipose tissue, cancer, cardiovascular comorbidities, skeletal muscle, the liver, kidney, and more. This book is a must-have reference for students and educational teams in biology, physiology and medicine, and researchers. Synthesizes actual knowledge on mitochondrial function Provides an integrated vision of each tissue in the etiology of obesity and type 2 diabetes Identifies the interactive networks that involve alteration in mitochondrial mass and function in disease progression Highlights the role played by mitochondria in the prevention and treatment of obesity and type 2 diabetes

Polycystic Ovary Syndrome

Author : Andrea Dunaif
Publisher : Springer Science & Business Media
Page : 361 pages
File Size : 28,2 MB
Release : 2008-01-12
Category : Medical
ISBN : 1597451088

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This volume includes the latest diagnostic criteria for PCOS and comprises the most up-to-date information about the genetic features and pathogenesis of PCOS. It critically reviews the methodological approaches and the evidence for various PCOS susceptibility genes. The book also discusses additional familial phenotypes of PCOS and their potential genetic basis. All four editors of this title are extremely prominent in the field of PCOS.

Mechanisms of Insulin Action

Author : Alan R. Saltiel
Publisher : Springer Science & Business Media
Page : 223 pages
File Size : 18,91 MB
Release : 2007-10-05
Category : Medical
ISBN : 0387722041

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More than 18 million people in the United States have diabetes mellitus, and about 90% of these have the type 2 form of the disease. This book attempts to dissect the complexity of the molecular mechanisms of insulin action with a special emphasis on those features of the system that are subject to alteration in type 2 diabetes and other insulin resistant states. It explores insulin action at the most basic levels, through complex systems.

Osteosarcopenia: Bone, Muscle and Fat Interactions

Author : Gustavo Duque
Publisher : Springer Nature
Page : 383 pages
File Size : 42,84 MB
Release : 2019-11-06
Category : Science
ISBN : 3030258904

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This edited work presents the most current evidence on osteosarcopenia from bench to bedside, which is expected to facilitate the understanding of this syndrome and to develop preventive and therapeutic strategies. With our aging population, chronic diseases such as osteoporosis and sarcopenia are becoming highly prevalent. Fortunately, our understanding of the bone and muscle interactions has increased in recent years. This has allowed to the coining of the term osteosarcopenia to describe a syndrome in which these two diseases overlap. This overlap between osteoporosis and sarcopenia has major negative effects not only on our older adults but also on health systems worldwide. Readers will find a highly translational approach that starts with a summary of recent discoveries on stem cells biology, muscle and bone interactions – including the role of local bone and muscle fat – followed by comprehensive reviews on myokines (i.e. myostatin), osteokines (i.e. osteocalcin) and adipokines (i.e. interleukins) as major players and determinants of bone and muscle loss with aging. In addition, the role of sex steroids (i.e. estrogens, androgens), and calciotropic hormones (i.e. parathyroid hormone, vitamin D) in the pathogenesis of this syndrome is also reviewed. Moreover, using practical diagnostic and therapeutic tips, this book summarizes the clinical characteristics of osteosarcopenic patients thus facilitating the diagnosis and treatment of this syndrome in clinical practice. Finally, the book presents the case for the Falls and Fractures Clinic as the optimal model of care for this syndrome, aimed to avoid fragmentation and optimize osteosarcopenia care, and simultaneously prevent falls and fractures in older persons. This book offers relevant information on the mechanisms of osteosarcopenia, and a practical guide on how to identify and treat this geriatric syndrome and its adverse outcomes, which are dramatically affecting our aging population. The work is written by leaders in the field and is especially suited not only to any researcher in the musculoskeletal arena but also to medical specialists and allied health professionals involved in the care of older persons.

The Secretory Granule

Author : Alan M. Poisner
Publisher :
Page : 444 pages
File Size : 29,19 MB
Release : 1982
Category : Medical
ISBN :

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Insulin Resistance

Author : Gerald M. Reaven
Publisher : Springer Science & Business Media
Page : 388 pages
File Size : 44,51 MB
Release : 1999-04
Category : Medical
ISBN : 9780896035881

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In Insulin Resistance: The Metabolic Syndrome X, outstanding investigators thoughtfully summarize our current understanding of how insulin resistance and its compensating hyperinsulinemia (Syndrome X) play a major role in the pathogenesis and clinical course of high blood pressure and cardiovascular disease-the so-called diseases of Western civilization-as well as polycystic ovary disease. Under the aegis of Gerald Reaven, the discoverer of Syndrome X, the distinguished authorities writing here detail for the first time the pathophysiological consequences and the clinical syndromes, excluding Type 2 diabetes, related to insulin resistance. They also examine the genetic and lifestyle factors that contribute to the wide differences in insulin action that exist in the population at large. Each author has been encouraged to present a point of view that reflects their unique insights. The first authoritative book on the subject, Insulin Resistance: The Metabolic Syndrome X illuminates the special importance of insulin resistance as a major cause of hypertension, heart disease, and polycystic ovary syndrome. Its thoughtful and detailed approach will make it an essential reference for basic and clinical researchers seeking to understand these critical phenomena.

Obesity and Lipotoxicity

Author : Ayse Basak Engin
Publisher : Springer
Page : 618 pages
File Size : 36,37 MB
Release : 2017-06-05
Category : Science
ISBN : 331948382X

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Due to the resultant health consequences and considerable increase in prevalence, obesity has become a major worldwide health problem. “Obesity and Lipotoxicity” is a comprehensive review of the recent researches to provide a better understanding of the lipotoxicity-related mechanisms of obesity and the potential for the development of new treatment strategies. This book overviews the biochemical pathways leading to obesity-related metabolic disorders that occur subsequent to lipotoxicity. Chapters examine the deleterious effects of nutrient excess at molecular level including the cellular and molecular aspects of breast cancer, resistance to leptin, insulin, adiponectin, and interconnection between the circadian clock and metabolic pathways during high-fat feeding. “Lipotoxicity and Obesity” will be a useful resource for clinicians and basic science researchers, such as biochemists, toxicologists, immunologists, nutritionists, adult and pediatric endocrinologists, cardiologists, as well as students who are thought in this field.

High Calorie Diet and the Human Brain

Author : Akhlaq A. Farooqui
Publisher : Springer
Page : 325 pages
File Size : 45,59 MB
Release : 2015-03-25
Category : Medical
ISBN : 3319152548

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The purpose of this monograph is to present readers with a comprehensive and cutting edge description of neurochemical effects of diet (beneficial and harmful effects) in normal human brain and to discuss how present day diet promotes pathogenesis of stroke, AD, PD, and depression in a manner that is useful not only to students and teachers but also to researchers, dietitians, nutritionists and physicians. A diet in sufficient amount and appropriate macronutrients is essential for optimal health of human body tissues. In brain, over-nutrition, particularly with high-calorie diet, not only alters cellular homeostasis, but also results in changes in the intensity of signal transduction processes in reward centers of the brain resulting in food addiction. Over-nutrition produces detrimental effects on human health in general and brain health in particular because it chronically increases the systemic and brain inflammation and oxidative stress along with induction of insulin resistance and leptin resistance in the brain as well as visceral organs. Onset of chronic inflammation and oxidative stress not only leads to obesity and heart disease, but also promotes type II diabetes and metabolic syndrome, which are risk factors for both acute neural trauma (stroke) and chronic age-related neurodegenerative and neuropsychological disorders, such as Alzheimer disease (AD), Parkinson disease (PD) and depression.

Mitochondria in Pathogenesis

Author : John J. Lemasters
Publisher : Springer Science & Business Media
Page : 533 pages
File Size : 16,40 MB
Release : 2007-05-08
Category : Science
ISBN : 0306468352

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Mitochondria are organelles in each cell outside the nucleus and are the energy source of all cells. As such, they are crucial to the healthy functioning of cells. Recent research has shown that mitochondrial dysfunction underlies a broad spectrum of disease, from maternally inherited genetic disorders to metabolism defects, aging, stroke, and neurodegenerative diseases such as Parkinson's, Alzheimer's, and Lou Gehrig's disease. This book brings together top researchers whose work in examining the pathophysiologic processes will lead to new strategies for prevention and treatment.