The pathophysiology of obesity

Obesity is a multi-cause syndrome. Overfeeding and low exercise produces excess of body fat. There are individual and population differences in energy balance, (ethnical, diet behavior, longer life expectancies). Genetic factors may influence the setting of obesity, but the calorie intake, physical activity, and lifestyle are critical determinants. As a consequence of the complex mechanisms involved in the pathogenesis of this syndrome and its complications, each model used in the diagnostic and therapeutic approach are partial. New evidences on the genetic and neuroendocrine factors in obesity are emerging, however, a holistic model is needed to understand this syndrome where biologic, psychological and social factors act together in a very intricate way. Using this model, better understanding in prevention and treatment is expected.     

Greasing the wheels of managing overweight and obesity with omega-3 fatty acids

The epidemic of overweight and obesity around the world and in the US is a major public health challenge, with 1.5 billion overweight and obese adults worldwide, and 68% of US adults and 31% of US children and adolescents overweight or obese. Obesity leads to serious health consequences, including an increased risk of type 2 diabetes mellitus and heart disease. Current preventive and medical treatments include lifestyle modification, medication, and bariatric surgery in extreme cases; however, they are either not very efficacious or are very expensive. Obesity is a complex condition involving the dysregulation of several organ systems and molecular pathways, including adipose tissue, the pancreas, the gastrointestinal tract, and the CNS. The role of the CNS in obesity is receiving more attention as obesity rates rise and treatments continue to fail. While the role of the hypothalamus in regulation of appetite and food intake has long been recognized, the roles of the CNS reward systems are beginning to be examined as the role of environmental influences on energy balance are explored.Omega-3 polyunsaturated fatty acids are essential nutrients that play a beneficial role in several disease processes due to their anti-inflammatory effects, modulation of lipids, and effects on the CNS. Omega-3 fatty acids, specifically EPA and DHA, have shown promising preliminary results in animal and human studies in the prevention and treatment of obesity. Given their effects on many of the pathways involved in obesity, and specifically in the endocannabinoid and mesocorticolimbic pathways, we hypothesize that EPA and DHA supplementation in populations can reduce the reward associated with food, thereby reduce appetite and food intake, and ultimately contribute to the prevention or reduction of obesity. If these fatty acids do harbor such potential, their supplementation in many parts of the world may hold great promise in reducing the global burden of obesity.     

European Guidelines for Obesity Management in Adults

Obesity is a chronic metabolic disease characterised by an increase of body fat stores. It is a gateway to ill health, and it has become one of the leading causes of disability and death, affecting not only adults but also children and adolescents worldwide. In clinical practice, the body fatness is estimated by BMI, and the accumulation of intra-abdominal fat (marker for higher metabolic and cardiovascular disease risk) can be assessed by waist circumference. Complex interactions between biological, behavioural, social and environmental factors are involved in regulation of energy balance and fat stores. A comprehensive history, physical examination and laboratory assessment relevant to the patient''s obesity should be obtained. Appropriate goals of weight management emphasise realistic weight loss to achieve a reduction in health risks and should include promotion of weight loss, maintenance and prevention of weight regain. Management of co-morbidities and improving quality of life of obese patients are also included in treatment aims. Balanced hypocaloric diets result in clinically meaningful weight loss regardless of which macronutrients they emphasise. Aerobic training is the optimal mode of exercise for reducing fat mass while a programme including resistance training is needed for increasing lean mass in middle-aged and overweight/obese individuals. Cognitive behavioural therapy directly addresses behaviours that require change for successful weight loss and weight loss maintenance. Pharmacotherapy can help patients to maintain compliance and ameliorate obesity-related health risks. Surgery is the most effective treatment for morbid obesity in terms of long-term weight loss. A comprehensive obesity management can only be accomplished by a multidisciplinary obesity management team. We conclude that physicians have a responsibility to recognise obesity as a disease and help obese patients with appropriate prevention and treatment. Treatment should be based on good clinical care, and evidence-based interventions; should focus on realistic goals and lifelong multidisciplinary management.Key Words: European guidelines, Obesity management, Multidisciplinary, Primary care, OMTF, COMs     

Surgical treatment of obesity: a review

Obesity is a chronic disease due to excess fat storage, a genetic predisposition, and strong environmental contributions. This problem is worldwide, and the incidence is increasing daily. There are medical, physical, social, economic, and psychological comorbid conditions associated with obesity. There is no cure for obesity except possibly prevention. Nonsurgical treatment has been inadequate in providing sustained weight loss. Currently, surgery offers the only viable treatment option with longterm weight loss and maintenance for the morbidly obese. Surgeries for weight loss are called bariatric surgeries. There is no one operation that is effective for all patients. Gastric bypass operations are the most common operations currently used. Because there are inherent complications from surgeries, bariatric surgeries should be performed in a multidisciplinary setting. The laparoscopic approach is being used by some surgeons in performing the various operations. The success rate--usually defined as >50% excess weight loss that is maintained for at least five years from bariatric surgery--ranges from 40% in the simple to >70% in the complex operations. The weight loss from surgical treatment results in significant improvements and, in some cases, complete resolution of comorbid conditions associated with obesity. Patients undergoing surgery for obesity need lifelong nutritional supplements and medical monitoring.     

Gallbladder disease and obesity

Gallbladder disease is a very common diagnosis and implies great economic cost. Gallbladder disease is a multifactorial process involved with host and environmental factors. Obesity is considered one of the most important risk factor associated with gallstone disease and is very important mainly due its increased prevalence worldwide. Several changes in cholesterol metabolism tend to increase gallbladder cholesterol secretion in conjunction with motility disturbances, which aids in gallstone growth. In this work, epidemiologic and pathophysiologic factors related with obesity and gallstone disease are discussed.     

Obesity in neurobiology

Obesity reflects an imbalance between energy uptake and expenditure that is mediated by behavior. Obesity is a growing epidemic and a major risk factor for neurobiological diseases like stroke, dementia, intracranial hypertension and sleep disorders. Conversely, obesity can also be induced by neurobiological disorders and drugs. The etiology of obesity is complex and includes biology, behavior and environment. Physicians are faced with the need to manage obesity while strategies for prevention and sustained weight reduction are limited. Present treatment options comprise lifestyle modification, diet, pharmacotherapy and bariatric surgery. Considerable headway has been made into elucidating the neurobiological underpinnings of obesogenic behavior. There is now a growing understanding of the metabolic, hormonal and behavioral circuitries that contribute to the complex and redundant system for energy balance. Changing the net balance of this system to prevent or reduce obesity requires multimodal and long-term interventions.     

Obesity: What is an elderly population growing into?

Objectives

Obesity is currently a major public health concern; however, there is little data available on the prevalence and impact of obesity within the elderly population. This review examines the prevalence and health effects of obesity among individuals aged ≥50.

Methods

PubMed (1996–2008) and PsychInfo (2002–2008) search engines were used to retrieve qualified peer-reviewed articles focusing on obesity or a health condition correlated with obesity using BMI or other weight index as a defining variable; and studies limited to the elderly (age 60+) or pre-elderly (50+).

Results

Worldwide, the elderly population is increasingly becoming obese regardless of socio-economic status. Among elderly persons, obesity increases the risks for a variety of morbidity conditions including cancers, diabetes, hypertension, stroke, heart disease, metabolic syndrome, obstructive sleep apnea syndrome, osteoarthritis, depression, disability, and lower scores on quality of life measures. In some reports, obesity has been linked to Alzheimer's disease and other forms of cognitive decline. Obesity significantly increases healthcare costs and nursing homes are currently ill equipped to address the needs of the rising number of obese residents.

Conclusions

Obesity is increasing in the elderly population worldwide and is expected to continue to rise. Obesity is associated with disease and disability in addition to escalating healthcare costs, and hospitals and nursing homes are ill equipped to serve the obese elderly. It is imperative that research efforts and funding be devoted to studying the effects and the reduction of obesity in the elderly population.     

Obesity, blood vessels and metabolic syndrome

Obesity is rising worldwide at an alarming rate and so is the incidence of obesity-related disorders, such as the metabolic syndrome, type 2 diabetes and cardiovascular diseases. The obesity-dependent vascular damage appears to be derived from a variety of changes in the adipose tissue, leading to a chronic inflammatory state and dysregulation of adipocyte-derived factors. This, in turn, impairs vascular homeostasis by determining an unbalance between the protective effect of the nitric oxide pathway and the unfavourable action of the endothelin-1 system. In addition, hyperinsulinemia and insulin resistance contribute to vascular dysfunction because the opposing endothelium-dependent vasodilating and vasoconstrictor effects of insulin are shifted towards a predominant vasoconstriction in patients with obesity. Importantly, emerging evidence suggests that the vascular dysfunction of obesity is not only limited to the endothelium but also involves the other layers of the vessel wall. In particular, obesity-related changes in vascular smooth muscle seem to disrupt the physiological facilitatory action of insulin on the responsiveness to vasodilator stimuli, whereas the adventitia and the perivascular fat appear to be a source of proinflammatory and vasoactive factors that may contribute to endothelial and smooth muscle cell dysfunction and to the pathogenesis of vascular disease.     

An EASO Position Statement on Multidisciplinary Obesity Management in Adults

Obesity has proven to be a gateway to ill health. It has already reached epidemic proportions becoming one of the leading causes of death and disability in Europe and world-wide. Obesity plays a central role in the development of a number of risk factors and chronic diseases like hypertension, dyslipidaemia and type 2 diabetes mellitus inducing cardiovascular morbidity and mortality. Therefore weight management plays a central role in controlling the respective risk factors and their consequences. Obesity is a complex condition of multifactorial origin. Biological but also psychological and social factors interfere to lead to excess body weight and its deleterious outcomes. Obesity management cannot focus any more only on weight (and BMI) reduction. More attention is to be paid to waist circumference (or waist-to-hip ratio, especially in females), the improvement in body composition (measured with body composition tracking systems like BOD POD, dual energy X-ray absorptiometry or bioelectrical impedance analysis) which is focusing on ameliorating or maintaining fat-free mass and decreasing fat mass. Management of co-morbidities, improving quality of life and well-being of obese patients are also included in treatment aims. This statement emphasises the importance of a comprehensive approach to obesity management.Key Words: Obesity management, OMTF, Weight loss, Multidisciplinary, Treatment, Statement     

Cancer and obesity

The prevalence of obesity is increasing worldwide. Obesity is also a major risk factor for developing chronic diseases, including malignancies thereby increasing the risk of several types of tumors such as breast, endometrium, colon, prostate and kidney cancer. The mechanisms associated with obesity and insulin resistance, hormonal regulation and other proinflammatory factors are also involved in neoplastic processes including: cell proliferation, carcinogenesis, and angiogenesis vascularization. In addition to contributing to cancer pathogenesis obesity is associated with comorbidities and poor prognosis in cancer patients. The aim of this review is to describe some of the mechanisms involved in the association of obesity and malignancies.     

肥胖症遗传学研究进展

肥胖症日益严重威胁公众健康,肥胖是环境和遗传因素相互作用的结果.本文主要从单基因病变、单核苷酸多态性(single nucleotide polymorphisms,SNPs)、神经机制和双胞胎研究等方面综述近年来的肥胖症遗传学进展.20余个明确导致人类常染色体显性遗传形式肥胖的单基因已经被发现,全基因组关联研究用来辨别在普通人群中肥胖存在的共同遗传变异,肥胖基因FTO(fat mass and obesity associated)被证明是一种能够使DNA的3-甲基胸腺嘧啶在体外去甲基化的双加氧酶,是最早发现的与人肥胖相关的基因.肥胖是一种代谢性疾病,更是一种神经行为障碍.瘦素是脂肪细胞衍生激素,它能够影响能量平衡的控制核心.     

肥胖症遗传学研究进展

肥胖症日益严重威胁公众健康,肥胖是环境和遗传因素相互作用的结果.本文主要从单基因病变、单核苷酸多态性(single nucleotide polymorphisms,SNPs)、神经机制和双胞胎研究等方面综述近年来的肥胖症遗传学进展.20余个明确导致人类常染色体显性遗传形式肥胖的单基因已经被发现,全基因组关联研究用来辨别在普通人群中肥胖存在的共同遗传变异,肥胖基因FTO(fat mass and obesity associated)被证明是一种能够使DNA的3-甲基胸腺嘧啶在体外去甲基化的双加氧酶,是最早发现的与人肥胖相关的基因.肥胖是一种代谢性疾病,更是一种神经行为障碍.瘦素是脂肪细胞衍生激素,它能够影响能量平衡的控制核心.     

Obesity--a global public health problem

Obesity and overweight, as a part of the metabolic syndrome, are well known risk factors for the development of diabetes, hypertension, coronary heart disease, hyperlipidemia, stroke, sleep apnea syndrome, osteoarthritis and certain forms of cancer. Cardiovascular disease remains the leading killer in industrialized countries, where it accounts for 40% of deaths. Obesity is defined either by increased waist circumference, waist to hip ratio, or body mass index. Obesity results from an interaction of genes and lifestyle. As people in both developed and developing countries eat more and more energy dense food, and have ever less physical activity, the number of overweight and obese people increases to epidemic proportions. Abdominal obesity plays a key role in the pathophysiology of metabolic disorders, is associated with insulin resistance, and predicts the development of type 2 diabetes and subsequent coronary artery disease. In the general population, obesity is associated with an increased mortality, but paradoxically, a positive correlation between body mass index and survival in congestive heart failure has been reported. In secondary prevention, obesity is underrecognized, underdiagnosed and undertreated in persons with cardiovascular diseases. Weight loss and prevention of weight gain have to be considered one of the most important strategies to reduce the incidence of cardiovascular disease. Increased physical activity and appropriate diet are the cornestones of treatment. Considering the high prevalence of overweight and obesity in Croatia, there is urgent necessity to improve the level of knowledge and skills in understanding obesity by health care services, and to implement appropriate professional strategy to achieve the desired lifestyle modifications.     

Metabolic Mechanisms in Obesity and Type 2 Diabetes: Insights from Bariatric/Metabolic Surgery

Obesity and the related diabetes epidemics represent a real concern worldwide. Bariatric/metabolic surgery emerged in last years as a valuable therapeutic option for obesity and related diseases, including type 2 diabetes mellitus (T2DM). The complicated network of mechanisms involved in obesity and T2DM have not completely defined yet. There is still a debate on which would be the first metabolic defect leading to metabolic deterioration: insulin resistance or hyperinsulinemia? Insight into the metabolic effects of bariatric/metabolic surgery has revealed that, beyond weight loss and food restriction, other mechanisms can be activated by the rearrangements of the gastrointestinal tract, such as the incretinic/anti-incretinic system, changes in bile acid composition and flow, and modifications of gut microbiota; all of them possibly involved in the remission of T2DM. The complete elucidation of these mechanisms will lead to a better understanding of the pathogenesis of this disease. Our aim was to review some of the metabolic mechanisms involved in the development of T2DM in obese patients as well as in the remission of this condition in patients submitted to bariatric/metabolic surgery.Key Words: Obesity, Type 2 diabetes, Metabolic surgery, Hyperinsulinemia, Insulin resistance, Surgical food restriction, Incretins     

Obesity, insulin resistance and diabetes: sex differences and role of oestrogen receptors

Obesity increases the risk of coronary artery disease through insulin resistance, diabetes, arterial hypertension and dyslipidemia. The prevalence of obesity has increased worldwide and is particularly high among middle-aged women and men. After menopause, women are at an increased risk to develop visceral obesity due to the loss of endogenous ovarian hormone production. Effects of oestrogens are classically mediated by the two nuclear oestrogen receptors (ERs) α and β. In addition, more recent research has shown that the intracellular transmembrane G-protein-coupled oestrogen receptor (GPER) originally designated as GPR30 also mediates some of the actions attributed to oestrogens. Oestrogen and its receptors are important regulators of body weight and insulin sensitivity not only in women but also in men as demonstrated by ER mutations in rodents and humans. This article reviews the role of sex hormones and ERs in the context of obesity, insulin sensitivity and diabetes as well as the related clinical issues in women and men.     

Investigations of the endocannabinoid system in adipose tissue: effects of obesity/ weight loss and treatment options

Obesity is a world wide epidemic; it is becoming more usual to be overweight or obese than to be normal weight. Obesity increases the risk of an extensive range of diseases such as cardiovascular disease, diabetes mellitus type 2, hypertension, depression and some types of cancer. Adipose tissue is more than a storage organ for surplus energy - it is also a setting for complex metabolic processes and adipose tissue releases substances that interact with other parts of the body to influence several systems including food intake and energy metabolism. The endocannabinoid system (ECS) is one of the signalling systems that control feeding behaviour. The ECS is implicated in many functions, such as pain, memory, addiction, inflammation, and feeding, and could be considered a stress recovery system. It also seems to integrate nutrient intake, metabolism and storage maintaining homeostatic balance. The ECS is a recently discovered system, and research indicates hyperactivity in obesity. The aim of this thesis is to elaborate on the relationships of this widespread system and its elements in adipose tissue in obesity. Study I is a 4 weeks rat intervention study to investigate whether weight independent effect of Rimonabant treatment exists. We found that food intake-tolerance development could be circumvented by cyclic administration of Rimonabant and implications of weight independent effects of treatment. Study II is a cross-sectional study to establish the expression of cannabinoid receptor 1 from various adipose tissue depots of lean and obese persons. In this study we conclude, that the subcutaneous adipose tissue express more CBR1 than the visceral depot in lean, but comparable levels in obese. Study III is a 10 weeks human intervention study to asses the effects on the ECS of 10% weight loss. We found reduction in the ECS in obesity that normalised with weight loss. Our results clearly show the presence of all the components of the ECS in human adipose tissue, and suggest that the ECS is reduced in adipose tissue in obesity. Our results do not support the hypothesis of hyperactivity of the ECS in human obesity. Possible future treatment of obesity with CBR1 antagonist could involve cyclic treatment of specific peripheral compounds.     

Clinical,molecular genetics and therapeutic aspects of syndromic obesity

Obesity has become a major health problem worldwide. To date, more than 25 different syndromic forms of obesity are known in which one (monogenic) or multiple (polygenic) genes are involved. This review gives an overview of these forms and focuses more in detail on 6 syndromes: Prader Willi Syndrome and Prader Willi like phenotype, Bardet Biedl Syndrome, Alström Syndrome, Wilms tumor, Aniridia, Genitourinary malformations and mental Retardation syndrome and 16p11.2 (micro)deletions. Years of research provided plenty of information on the molecular genetics of these disorders and the obesity phenotype leading to a more individualized treatment of the symptoms, however, many questions still remain unanswered. As these obesity syndromes have different signs and symptoms in common, it makes it difficult to accurately diagnose patients which may result in inappropriate treatment of the disease. Therefore, the big challenge for clinicians and scientists is to more clearly differentiate all syndromic forms of obesity to provide conclusive genetic explanations and eventually deliver accurate genetic counseling and treatment. In addition, further delineation of the (functions of the) underlying genes with the use of array- or next-generation sequencing-based technology will be helpful to unravel the mechanisms of energy metabolism in the general population.     

Obesity in the 21st century. Progress in etiopathogenesis and treatment

Obesity is complex in its etiology and treatment. Its global incidence is increasing significantly. Favoring weight-loss can only bring beneficial effects. Obesity is a chronic condition with multifactorial origin. The discovery of the ob gene and its product, the OB protein or Leptin, neuropeptide Y, and the alterations of the metabolism of lipogenic tissues that inhibit appetite are significant advances in the understanding of its etiopathogenesis and treatment. This new knowledge will change the philosophy of the management of obesity. Obesity responds poorly to nonsurgical therapies. Its treatment must be long-term in spite of the considerable social and biological pressure that favor the regaining of weight. Treatment of the obese patient must be performed by a multidisciplinary team, and should include a hypoenergetic diet, exercise program, behavioral modifications, and in some instances, family therapy. The treatment of obesity should be tailored for each individual. Drug use in the treatment of obesity is not a substitute for modifying the individual's diet and physical activity. Bariatric surgery is indicated only when the BMI is greater than 30 kg/m2. Physicians and patients must interact closely and assess possible risks that are involved in its treatment against real benefits. A good relation between practitioner and patient is essential.     

Obesity and obstructive sleep apnea: Or is it OSA and obesity?

Obstructive sleep apnea (OSA) consists of repetitive choking spells due to sleep-induced reduction of upper airway muscle tone. Millions of adults and children live unaware of this condition, which can have a profound affect on their health and quality of life. Obesity, gender, genetic, and hormonal factors mediate risk for OSA and interact in a multifaceted manner in the pathogenesis of this disease. Obesity is the most established and primary risk factor given that body mass index, visceral fat, and neck circumference are major predictors in the clinical expression of OSA. Many studies have shown weight loss or gain significantly impacts OSA severity. More recently, accumulating evidence indicates OSA promotes weight gain, obesity, and type II diabetes in a variety of ways, such that obesity and OSA form multiple interleaved vicious cycles. Thus, creative strategies to increase physical activity, improve diet, and otherwise facilitate weight management become particularly vital given the epidemics of obesity and OSA in the United States. In this regard, the American College of Sports Medicine recently launched the "Exercise is Medicine" (initiative exerciseismedicine.org). In the future, medications may emerge to treat obesity, OSA, and their sequelae with minimal side effects. However, there are effective ways to approach these problems now without waiting for "the magic pill".     

The epidemic of obesity and changes in food intake: the Fluoride Hypothesis

The epidemic of obesity is worldwide. It will be followed by an epidemic of diabetes. Although there is a genetic basis for obesity and diabetes, the current epidemic reflects the failure of our ancient genes to cope with a modern toxic environment. To put it another way, the genetic background loads the gun, but the environment pulls the trigger. Diet, lifestyle and exercise are the cornerstones of current approaches to treating obesity. However, these approaches that depend on individuals making lifestyle changes have been ineffective in preventing the epidemic. An alternative model views obesity as an epidemiological disease with food(s) and other environmental agents acting on the host to produce disease. The consumption patterns for many foods have changed over the past 30 years, but the increase in the consumption of high-fructose corn syrup (HFCS) for soft drinks is far and away the largest. Moreover, the rise in HFCS intake is an environmental insult that has occurred at exactly the same time as obesity began to increase in prevalence. Rising soft drink consumption is associated with a decrease in milk consumption and a decrease in calcium intake, which has an inverse relationship to body mass index (BMI). To combat the epidemic of obesity, we need new strategies that flow from the epidemiological model. The Fluoride Hypothesis for obesity proposes that we can make environmental changes that when made, will reduce the epidemic of obesity, in much the same way as fluoride reduced the incidence of dental disease. Fluoride-like strategies can work without the personal effort required by changes in lifestyle. In this context, fluoride is also an acronym for treatment and prevention of obesity: For Lowering Universal Obesity Rates are Implement ideas that Don't demand Effort (FLUORIDE).