Obesity and Metabolic Syndrome Overview

Obesity represents one of the most serious global health issues with ;310 million people presently affected. It develops because of a mismatch between energy intake and expenditure that results from behavior (feeding behavior and time spent active) and physiology (resting metabolism and expenditure when active). Both of these traits are affected by environmental and genetic factors. The dramatic increase in the numbers of obese people in Western societies reflects mostly changing environmental factors and is linked to reduced activity and perhaps also increased food intake. However, in all societies and subpopulations, there are both obese and nonobese subjects. These differences are primarily a consequence of genetic factors as is revealed by the high heritability for body mass index. Most researchers agree that energy balance and, hence, body weight are regulated phenomena. There is some disagreement about exactly how this regulation occurs. However, a common model is the ''lipostatic'' regulation system, whereby our energy stores generate signals that are compared with targets encoded in the brain, and differences between these drive our food intake levels, activity patterns, and resting and active metabolisms. Considerable advances were made in the last decade in understanding the molecular basis of this lipostatic system. Some obese people have high body weight because they have broken lipostats, but these are a rare minority. This suggests that for the majority of obese people, the lipostat is set at an inappropriately high level. When combined with exposure to an environment where there is ready availability of food at low energy costs to obtain it, obesity develops. The evolutionary background to how such a system might have evolved involves the evolution of social behavior, the harnessing of fire, and the development of weapons that effectively freed humans from the risks of predation. The lipostatic model not only explains why some people become obese whereas others do not, but also allows us to understand why energy-controlled diets do not work. Drug-based solutions to the obesity problem that work with the lipostat, rather than against it, are presently under development and will probably be in regular use within 5-10 y. However, several lines of evidence including genetic mapping studies of quantitative trait loci associated with obesity suggest that our present understanding of the regulatory system is still rudimentary. In particular, we know nothing about how the target body weight in the brain is encoded. As our understanding in this field advances, new drug targets are likely to emerge and allow us to treat this crippling disorder. J. Nutr. 134: 1S-16S, 2004. KEY WORDS: obesity genetics environment review 4 Abbreviations used: AgRP, Agouti-related protein; a-MSH, a-melanocytestimulating hormone; ARC, arcuate nucleus; BMI, body mass index; BMR, basal metabolic rate; CART, cocaine and amphetamine-related transcript; db/db, mutant mouse lacking functional leptin receptors; fa/fa, mutant rat lacking functional leptin receptors; GABA, g-amino butyric acid; MC1-R, MC3-R, and MC4-R, melanocortin-1, -3, and -4 receptors; NPY, neuropeptide Y; ob/ob, mutant mouse lacking ability to produce leptin; POMC, pro-opiomelanocortin; PVN, paraventricular nucleus; PYY 3-36 , peptide YY 3-36 ; QTL, quantitative trait loci; RMR, resting metabolic rate; TNF-a, tumor necrosis factor-a; tub/tub, fat mutant mouse.

Nutrition in the Prevention and Treatment of Disease, 2013

Complex and incompletely defined interactions between the environment and genetics determine each individual’s height and weight, as well as other human quantitative traits.1 The result is a population in which individuals vary widely for height and weight, but no one factor can be identified as controlling either trait. In humans, long-term adult weight is relatively stable, as evidenced by the difficulty of sustaining intentional weight loss and the automatic return to previous weight following brief periods of overeating. This drive to constancy of body weight is due to both behavioral and physiological alterations that accompany weight change. Convincing evidence of the biological basis of the regulation of body fat stores comes from the identi-fication of more than 50 single-gene mutations and Mendelian2 syndromes that result in spontaneous mas-sive obesity or in adipose tissue atrophy.

PLoS Genetics, 2006

T he use of modern molecular biology tools in deciphering the perturbed biochemistry and physiology underlying the obese state has proven invaluable. Identifying the hypothalamic leptin/melanocortin pathway as critical in many cases of monogenic obesity has permitted targeted, hypothesis-driven experiments to be performed, and has implicated new candidates as causative for previously uncharacterized clinical cases of obesity. Meanwhile, the effects of mutations in the melanocortin-4 receptor gene, for which the obese phenotype varies in the degree of severity among individuals, are now thought to be influenced by one's environmental surroundings. Molecular approaches have revealed that syndromes (Prader-Willi and Bardet-Biedl) previously assumed to be controlled by a single gene are, conversely, regulated by multiple elements. Finally, the application of comprehensive profiling technologies coupled with creative statistical analyses has revealed that interactions between genetic and environmental factors are responsible for the common obesity currently challenging many Westernized societies. As such, an improved understanding of the different ''types'' of obesity not only permits the development of potential therapies, but also proposes novel and often unexpected directions in deciphering the dysfunctional state of obesity.

About Science in School

Nestlé Nutrition Workshop Series: Pediatric Program, 2008

The prevention and treatment of childhood obesity have proven to be extremely difficult problems. Since the equation for maintaining energy balance is an extremely simple one, having only two terms, 'energy in' and 'energy out', the difficulties encountered in its application for obesity management are not immediately obvious. Among the problems that make practical application of the energy balance equation more difficult than expected are: (1) the precise feedback control system that is designed to maintain weight within a given range; (2) the aggressive resistance of the system to attempts to exceed its boundaries; (3) inaccurate assessment of energy intake in practice; (4) the dominant role of genes in determining body weight; (5) the polygenic nature of obesity and the fact that any single gene accounts for a small fraction of the genetic variation in weight; (6) underestimation of the genetic contribution to the current 'epidemic' of obesity; (7) the fact that 'modifiable' risk factors may be less modifiable than expected; (8) appreciation that family role modeling may be less influential than anticipated, and (9) the realization that our knowledge about the development of physical activity behaviors in childhood is extremely limited.

1986

Background: Obesity is a complex phenomenon that involves interactions between environmental and genetics factors. The genetic studies in animal models and humans has allowed great progress in the knowledge of body weight regulation. Identifying the hypothalamic leptin/melanocortin pathway as critical in many cases of monogenic obesity has permitted targeted, hypothesis-driven experiments to be performed, and has implicated new candidates as causative for previously uncharacterized clinical cases of obesity. Data sources: Narrative review. PubMed, Lilacs and ScieLo databases were searched with the terms "obesity", "genetics" and limited only for " all child 0-18 years". Results: Numerous studies in children and adolescents, have tried to identify candidate genes. At present, the results are not conclusive. Thus, is yet premature genotype obese child on a large scale for predictive testing. Meanwhile, the effects of mutations in the melanocortin-4 receptor gene, for which the obese phenotype varies in the degree of severity among individuals, are now thought to be influenced by one's environmental surroundings. Molecular approaches have revealed that syndromes previously assumed to be controlled by a single gene are conversely regulated by multiple elements. Conclusions: When specific treatments based on recent discoveries become available, genetic testing could help to discriminate different types of obesity that may respond differentially to therapeutic measures.

Public Health Nutrition, 2007

Objective: The aim was to review and update advances in genetics of obesity. Design: Analysis and interpretation of recent investigations about regulating the energy balance as well as about gene-nutrient interactions and current nutrigenomic research methods. Background and main statements: Obesity results from a long-term positive energy balance. However, its rising prevalence in developed and developing societies must reflect lifestyle changes, since genetic susceptibility remains stable over many generations. Like most complex diseases, obesity derives from a failure of adequate homoeostasis within the physiological system controlling body weight. The identification of genes that are involved in syndromic, monogenic and polygenic obesity has seriously improved our knowledge of body weight regulation. This disorder may arise from a deregulation at the genetic level (e.g. gene transcription or altered protein function) or environmental exposure (e.g. diet, physical activity, etc.). Conclusions: In practice, obesity involves the interaction between genetic and environmental factors.

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.

2025

The integration of digital and quantitative methods in landscape archaeology, while not new, continues to open up new ways of exploring and understanding historical environments. This session aims to provide a space for reflection and debate on the use of advanced technologies in landscape archaeology, such as Geographic Information Systems (GIS) (Conolly & Lake 2006; Farinetti 2011), Network Analysis (NA) (Brughmans & Peeples 2023), or Agent-Based Modelling (ABM) (Romanowska et al. 2021), among others. These tools have revolutionised how archaeologists study human interactions with the natural and built environment, enabling the reconstruction of landscapes, the revelation of hidden connections between settlements, the analysis of trade routes, and the evaluation of how environmental and human factors have shaped the evolution of different territories over time. Landscape archaeology has focused on understanding how human communities settled, exploited, perceived and transformed space across different historical periods. In this field, GIS allows for the representation and spatial analysis of archaeological data, identifying patterns of occupation, land use, and environmental change (e.g., Grau Mira et al. 2024). Meanwhile, Network Analysis introduces a relational perspective to landscape studies, revealing the connections and flows of goods, people, and ideas between different actors (e.g., De Soto 2019). Agent-Based Modelling (ABM) helps simulate complex scenarios of human interaction, demonstrating how individual and collective decisions might have shaped past landscapes (e.g., Gravel-Miguel & Wren 2018). These methods open new perspectives on how past communities interacted with their environment. This session invites participants to examine these approaches from different angles, whether in their individual application or in combination within broader analytical frameworks. The goal is to foster an interdisciplinary dialogue that explores the challenges, opportunities, and implications of using these technologies in landscape archaeology research. We welcome contributions that investigate archaeological landscapes using digital technologies and other innovative quantitative methods, that explore studies on land use and occupation, connectivity and mobility analysis, as well as reconstructions and modelling. We also consider papers that use relational perspectives, such as network analysis, to reveal patterns of interaction between communities, or that combine multiple approaches to offer an integrated view of past landscapes and explore new lines of research.

The Conversation, 2019

The end of the world as we've known it is here. The only question is, what's next?