Implications of the biology of weight regulation and obesity on the treatment of obesity (original) (raw)

Obesity A Biobehavioral Point of View

Annals of the New York Academy of Sciences, 1990

If you ask an overweight person, "Why are you fat?', you will, almost invariably, get the answer, "Because 1 eat too much." You will get this answer in spite of the fact that of thirteen studies, six find no significant differences in the caloric intake of obese versus nonobese subjects, five report that the obese eat significantly less than the nonobese, and only two report that they eat significantly more. It is hard to overcome this possibly incorrect belief about the cause of obesity when most practicing professionals and certainly every diet book is based on the assumption that excessive caloric intake is at fault. In spite of a failure rate approaching 90 to 95%, we still cling to dietary exhortations in our treatments, and suspect that lack of adherence to our recommendations is responsible for failure. Recent research in the field of biochemistry suggests that several newly discovered factors, as well as others that have been known for years but generally overlooked, may contribute to obesity in a way that is not easily remedied by dieting. Caloric restriction may lead to an adaptive metabolic response that reduces a person's daily energy needs, and to hormone and enzyme changes that lead to an enhanced rate of fat storage following caloric restriction. Adaptive responses may be associated with initial dispositional tendencies for some individuals to be heavier than others, and, together, these adaptive and dispositional tendencies may provide a basis for the continual frustration experienced by millions of persons who repeatedly diet to lose weight. We will review evidence for these adaptive and dispositional tendencies that resist weight loss efforts and then suggest an alternative approach to severe caloric restriction based on data from the Vanderbilt University Weight Management Program.

The Science of Obesity Management: An Endocrine Society Scientific Statement

Endocrine reviews, 2018

The prevalence of obesity, measured by body mass index, has risen to unacceptable levels in both men and women in the United States and worldwide with resultant hazardous health implications. Genetic, environmental, and behavioral factors influence the development of obesity, and both the general public and health professionals stigmatize those who suffer from the disease. Obesity is associated with and contributes to a shortened life span, type 2 diabetes mellitus, cardiovascular disease, some cancers, kidney disease, obstructive sleep apnea, gout, osteoarthritis, and hepatobiliary disease, among others. Weight loss reduces all of these diseases in a dose-related manner-the more weight lost, the better the outcome. The phenotype of "medically healthy obesity" appears to be a transient state that progresses over time to an unhealthy phenotype, especially in children and adolescents. Weight loss is best achieved by reducing energy intake and increasing energy expenditure. P...

Obesity: Pathophysiology and Clinical Management

Current Medicinal Chemistry, 2009

Obesity is a serious socioeconomic, and also increasingly clinical problem. Between -1 / 3 of population in the developed countries can be classified as obese. Four major etiological factors for development of obesity are genetic determinants, environmental fac tors, f ood i ntake a nd exercise. O besity i ncreases the risk of t he de velopment of v arious pathologic conditions including: insulin-resistant di abetes m ellitus, cardiovascular disease, non-alcoholic fatty l iver di sease, endocrine problems, and certain forms of cancer. Thus, obesity is a negative prognostic factor for longevity. In this review w e pr ovide br oad ove rview of pa thophysiology of obe sity w e a lso di scuss va rious a vailable, a nd e xperimental therapeutic methods. We also highlight functions of adipocytes including fat storing capacity and secretory activity resulting in numerous endocrine effects like leptin, IL-6, adiponectin, and resistin. The anti-obesity drugs are classified according to their primary action on energy balance. Major classes of these drugs are: appetite suppressants, inhibitors of fat absorption (i.e. orlistat), stimulators of thermogenesis and stimulators of fat mobilization. The appetite suppressants are further divided into noradrenergic agents, (i.e. phentermine, phendimetrazine, benzphetamine, diethylpropion), serotoninergic agents (i.e. dexfenfluramine), and mixed noradrenergic-serotoninergic agents (i.e. sibutramine). Thus, we highlight recent advances in the understanding of the central neural control of energy balance, current treatment strategies for obesity and the most promising targets for the development of novel anti-obesity drugs.

A Literature Review of Control and Prevention of Obesity – A Global Epidemic

March 2019 Vol.:14, Issue:4, 2019

Obesity is among the most common and costly chronic disease worldwide. A lack of effective options for long term weight reduction magnifies the enormity of this problem, individuals who successfully complete behavioral and dietary weight loss programs eventually regain most of lost weight. The basic science, clinical and epidemiological literature to assess current knowledge regarding mechanism excess body fat accumulation, the biological defense of excess fat mass and the tendency for lost weight to be regained. A major area of emphasis is the science of energy homeostasis, the biological process that maintains weight stability by actively matching energy intake to energy expenditure over time. The ongoing study of how genetic development and environmental forces affects the energy homeostasis system, growing evidence suggests that obesity is disorder of the energy homeostasis system, rather than simply arising from the passive accumulation of excess weight. Obesity is a chronic metabolic disease characterized by an increase of body fat stores. It is a gateways to ill health and has become one of the leading causes of disability and health problems that affect not only adults but also children and adolescents worldwide. It is important to highlight the available treatment for obesity and to assess their effectiveness, although obesity is an ancient disease, studies are constantly being conducted to improve treatment effectiveness that reduces side effects of any currents medications and identify new therapeutic targets. Because the treatment of obesity is a constantly evolving that treatment can be quite challenging.

Obesity and energy balance: is the tail wagging the dog

European Journal of Clinical Nutrition, 2011

The scientific study of obesity has been dominated throughout the twentieth century by the concept of energy balance. This conceptual approach, based on fundamental thermodynamic principles, states that energy cannot be destroyed, and can only be gained, lost or stored by an organism. Its application in obesity research has emphasised excessive appetite (gluttony), or insufficient physical activity (sloth), as the primary determinants of excess weight gain, reflected in current guidelines for obesity prevention and treatment. This model cannot explain why weight accumulates persistently rather than reaching a plateau, and underplays the effect of variability in dietary constituents on energy and intermediary metabolism. An alternative model emphasises the capacity of fructose and fructose-derived sweeteners (sucrose, high-fructose corn syrup) to perturb cellular metabolism via modification of the adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio, activation of AMP kinase and compensatory mechanisms, which favour adipose tissue accretion and increased appetite while depressing physical activity. This conceptual model implicates chronic hyperinsulinaemia in the presence of a paradoxical state of 'cellular starvation' as a key driver of the metabolic modifications inducing chronic weight gain. We combine evidence from in vitro and in vivo experiments to formulate a perspective on obesity aetiology that emphasises metabolic flexibility and dietary composition rather than energy balance. Using this model, we question the direction of causation of reported associations between obesity and sleep duration or childhood growth. Our perspective generates new hypotheses, which can be tested to improve our understanding of the current obesity epidemic, and to identify novel strategies for prevention or treatment.

Body Fat Regulation: Is It a Result of a Simple Energy Balance or a High Fat Intake?

Journal of the American College of Nutrition, 2010

The search for the causes of obesity has involved genetic abnormalities and endocrine and neural lesions. Although evidence suggests that genetics plays an important role in body weight regulation, rapid increases in obesity rates do not seem to be caused by significant genetic changes within populations. Total energy expenditure and total energy intake are not the only factors that regulate body fat. Nitrogen and carbohydrate balances are eased by the capacity of the organism for adjusting amino acids and glucose oxidation rates, respectively. Regarding fat, this mechanism is considerably less precise; a fat intake increase does not stimulate its oxidation on the same basis. In addition, dietary fat is stored very efficiently as body fat. Elevated carbohydrate ingestion enhances glycogen reserves, which usually are much smaller than the maximum capacity of storage and enlargement of these stores, thus stimulating this nutrient's oxidation. These data point to a very well controlled carbohydrate balance in the body. Various studies show lack of efficiency of the hyperlipidic diet in stimulating satiety. Signals arising from the gastrointestinal tract play a fundamental role in regulation of appetite and energy intake, and evidence indicates that the gastrointestinal and hormonal mechanisms involved in the suppression of appetite and in energy intake are compromised in obesity. A high-fat diet is important in its origin. Additional studies are necessary to explain the mechanisms that lead to adipose tissue retention resulting in a fat-rich diet.

Obesity and Metabolic Conditions

Sustainable Community Health, 2020

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Methodological approaches to assess body-weight regulation and aetiology of obesity

Proceedings of the Nutrition Society, 2000

Obesity, which is becoming one of the major health hazards in developed and developing societies, results from a long-term positive energy balance. Body-weight regulation and stability depend on an axis with three interrelated components: food intake, energy expenditure and adipogenesis, although there are still many unknown features concerning fuel homeostasis and energy balance. Biochemical processes are interconnected, and a separate consideration of each component is often useful for methodological purposes and to achieve a better understanding of the whole system. Thus, many different experimental approaches can be applied by using laboratory animals, cell culture or human subjects to unravel the molecular mechanisms which participate in body-weight regulation. Thus, both in vitro (cellular and subcellular models) and in vivo methods have dramatically increased our knowledge of weight control. Several strategies in obesity research are reported here, exploiting the opportunitie...