Feeding regulatory peptides: hopes and limits for the treatment of obesities

Excessive weight gain is directly related to a positive energy balance which is due to both a decreased physical activity and overeating. Obesity prevalence is increasing since thirty years and the treatment of obesities is particularly necessary to solve this public health and economical problem. The receptors of numerous hypothalamic neuropeptides are potential targets for such drug treatments. Hormones of the gastro-intestinal tract or produced by the adipose tissue directly interact with these central pathways to regulate feeding behavior. The use of leptin, an adipose tissue hormone that inhibits food intake, has not been conclusive because of the development of leptin resistance in obese subjects. Similar disappointing results have been obtained with antagonists of neuropeptide Y (NPY), one of the most potent orexigenic peptide. This was linked to the complexity and redundancy of the circuits involved in feeding regulation. Consequently, a multitherapy targeting several pathways simultaneously is probably the best option to cure obesity. Among these pathways, PYY 3-36 has been tested in man and some encouraging data have been obtained in animals with antagonists of some other orexigenic peptides such as orexins and melanin-concentrating hormone. A few gene therapy trials in the rat brain have restored interest for the leptin and NPY pathways. Their general use is however not planed in a next future. According to the type of obesity, these new treatments might be associated with either current (or almost current) drugs acting either on serotoninergic/catecholaminergic or cannabinoid pathways, or with surgery. Behavioral changes (food intake, exercise) and preventive actions during early life (in utero, young children) will remain for a while the best solutions to limit overweight development. The new treatments will help obese people to adhere to these behavioral changes by improving their efficiency to induce weight loss.     

Design patterns for wildlife‐related camera trap image analysis

This paper describes and explains design patterns for software that supports how analysts can efficiently inspect and classify camera trap images for wildlife‐related ecological attributes. Broadly speaking, a design pattern identifies a commonly occurring problem and a general reusable design approach to solve that problem. A developer can then use that design approach to create a specific software solution appropriate to the particular situation under consideration. In particular, design patterns for camera trap image analysis by wildlife biologists address solutions to commonly occurring problems they face while inspecting a large number of images and entering ecological data describing image attributes. We developed design patterns for image classification based on our understanding of biologists' needs that we acquired over 8 years during development and application of the freely available Timelapse image analysis system. For each design pattern presented, we describe the problem, a design approach that solves that problem, and a concrete example of how Timelapse addresses the design pattern. Our design patterns offer both general and specific solutions related to: maintaining data consistency, efficiencies in image inspection, methods for navigating between images, efficiencies in data entry including highly repetitious data entry, and sorting and filtering image into sequences, episodes, and subsets. These design patterns can inform the design of other camera trap systems and can help biologists assess how competing software products address their project‐specific needs along with determining an efficient workflow.     

Stochasticity in Natural Forage Production Affects Use of Urban Areas by Black Bears: Implications to Management of Human-Bear Conflicts

The rapid expansion of global urban development is increasing opportunities for wildlife to forage and become dependent on anthropogenic resources. Wildlife using urban areas are often perceived dichotomously as urban or not, with some individuals removed in the belief that dependency on anthropogenic resources is irreversible and can lead to increased human-wildlife conflict. For American black bears (Ursus americanus), little is known about the degree of bear urbanization and its ecological mechanisms to guide the management of human-bear conflicts. Using 6 years of GPS location and activity data from bears in Aspen, Colorado, USA, we evaluated the degree of bear urbanization and the factors that best explained its variations. We estimated space use, activity patterns, survival, and reproduction and modeled their relationship with ecological covariates related to bear characteristics and natural food availability. Space use and activity patterns were dependent on natural food availability (good or poor food years), where bears used higher human density areas and became more nocturnal in poor food years. Patterns were reversible, i.e., individuals using urban areas in poor food years used wildland areas in subsequent good food years. While reproductive output was similar across years, survival was lower in poor food years when bears used urban areas to a greater extent. Our findings suggest that bear use of urban areas is reversible and fluctuates with the availability of natural food resources, and that removal of urban individuals in times of food failures has the potential to negatively affect bear populations. Given that under current predictions urbanization is expected to increase by 11% across American black bear range, and that natural food failure years are expected to increase in frequency with global climate change, alternative methods of reducing urban human-bear conflict are required if the goal is to prevent urban areas from becoming population sinks.     

Trends in U.S. food prices, 1950-2007

The potential effect that food prices may have on the health of the U.S. population needs to be further explored, particularly in light of the rising food prices currently being observed. Declining food prices over time have been singled out as a main contributor, for example, to the rising trend in obesity. In this paper we use data from the Bureau of Labor Statistics, the American Chamber of Commerce Researchers Association, the Consumer Expenditure Survey, and the United States Department of Agriculture to analyze trends in various types of food prices, to create a food price index, and to estimate the price of a calorie. Results may be used by future researchers in estimating the health implications of these trends. We find that while the general trend in food prices has been declining, that of restaurant meal prices and prices of fruits and vegetables has risen over time. It is doubtful that the decline in food prices has been sufficiently large to account for the large increase in caloric intake that is said to have contributed to the obesity epidemic in the U.S.     

How NOT to Approach the Obesity Problem

FLATT, JP. How NOT to approach the obesity problem. The emphasis given to the energy balance equation has fostered the widespread belief that obesity is a problem of energy balance. This mistaken view has led to many unjustified and unfortunate interpretations, because obesity is, rather, a problem of the interaction between body composition and food intake regulation.     

Genes and obesity: a cause and effect relationship

The International Task Force on Obesity (IOTF) and the World Health Organization (WHO) have defined obesity as a 21st century epidemic. In countries with economies in transition and even in some urban areas in developing countries, progressive increase in obesity has been reported to be an emerging problem in recent years. Its causes include lifestyle changing, particularly consumption of high-calorie food, as well as an increasingly sedentary lifestyle. However, the genetic origin of obesity is well known and currently proven. Obesity usually results from interaction of certain gene polymorphisms with environment. Moreover, only a small number of cases of obesity (5%) result from mutations in specific genes (monogenic obesity), causing in some cases Mendelian syndromes with a very low incidence in the population. One hundred and thirty genes related to obesity have been reported, some of which are involved in coding of peptide transmitting hunger and satiety signals, while others are involved in adipocyte growth and differentiation processes, and still others are involved in regulation of energy expenditure. In addition, obesity is a chronic inflammatory state. In this regard, altered expression of genes related to insulin metabolism and adipose tissue inflammation is a basic process which may explain the etiology of obesity.     

The involvement of purinergic signalling in obesity

Obesity is a growing worldwide health problem, with an alarming increasing prevalence in developed countries, caused by a dysregulation of energy balance. Currently, no wholly successful pharmacological treatments are available for obesity and related adverse consequences. In recent years, hints obtained from several experimental animal models support the notion that purinergic signalling, acting through ATP-gated ion channels (P2X), G protein-coupled receptors (P2Y) and adenosine receptors (P1), is involved in obesity, both at peripheral and central levels. This review has drawn together, for the first time, the evidence for a promising, much needed novel therapeutic purinergic signalling approach for the treatment of obesity with a ‘proof of concept’ that hopefully could lead to further investigations and clinical trials for the management of obesity.     

The vanishing weight gap: Trends in obesity among adult food stamp participants (US) (1976–2002)

High rates of obesity among low-income populations have led some to question whether USDA's food assistance programs have contributed to this health problem. Using data from National Health and Nutrition Examination Surveys (NHANES), this study shows that the association between food assistance program participation and body weight measures has weakened over the past three decades. Earlier NHANES data show that program participants were more likely to be overweight than individuals who were eligible but not participating in the program. This was particularly true among white women. However, the more recent data show that these differences have vanished, as the BMI of the rest of the population has caught up to BMI levels of food stamps recipients.     

Body mass growth in common marmosets: Toward a model of pediatric obesity

While much is known about adult obesity in nonhuman primates, very little is known regarding development of childhood adiposity. As small monkeys that are easy to handle and have a relatively fast life history, common marmoset monkeys (Callithrix jacchus) offer interesting opportunities to examine the question of fat versus lean mass growth in a nonhuman primate. This article provides an overview of our understanding of early life growth in mass in marmoset monkeys, based primarily upon our past 20 years of research, culminating in our recent findings on early life obesity in this species. Common marmosets display variance in early life growth patterns that is related to both pre‐ and postnatal factors and the marmoset uterine environment is exquisitely designed to reflect resources available for the gestation of multiple offspring, making them an interesting model of developmental programming. We have demonstrated that obesity can be generated in very early life in captive marmosets, with excess adiposity evident by one month of age, making this species a potentially valuable model in which to study pediatric obesity and its sequelae. Birth weight is associated with adiposity in animals vulnerable to obesity. Early life exposure to higher fat diets enhances the chances of postweaning obesity development. However, overall higher food consumption is also associated with obesity development at later ages. One unexpected finding in our studies has been the relatively high body fat percentage of neonatal (12–18%) marmosets suggesting that hypotheses regarding the uniqueness of high human neonatal adiposity merit further examination. Am J Phys Anthropol, 2013. © 2012 Wiley Periodicals, Inc.     

Fast food prices,obesity, and the minimum wage

Recent proposals argue that a fast food tax may be an effective policy lever for reducing population weight. Although there is growing evidence for a negative association between fast food prices and weight among adolescents, less is known about adults. That any measured relationship to date is causal is unclear because there has been no attempt to separate variation in prices on the demand side from that on the supply side. We argue that the minimum wage is an exogenous source of variation in fast food prices, conditional on income and employment. In two-stage least-squares analyses, we find little evidence that fast food price changes affect adult BMI or obesity prevalence. Results are robust to including controls for area and time fixed effects, area time trends, demographic characteristics, substitute prices, numbers of establishments and employment in related industries, and other potentially related factors.     

肠道菌群与肥胖关系的研究进展

西方化的高脂饮食方式造成了越来越多的肥胖人群。高脂饮食在一定程度上可以改变肠道菌群的结构组成和功能,促进宿主对食物营养的吸收,从而增加体重形成肥胖。高脂饮食诱导的肥胖者肠道菌群的改变会导致宿主能量吸收增加,肠道通透性和炎症增加,而有减肥功能的短链脂肪酸合成能力下降。最近研究发现肠道菌群也可以通过影响中枢神经系统,尤其是下丘脑相关基因的表达来控制食欲,从而调控肥胖的形成。本文系统介绍了最近几年高脂饮食诱导肥胖的研究,总结了一些与肥胖形成有密切关系的肠道菌群以及其在肥胖形成中的作用机制,为进一步研究肠道菌群与肥胖之间的调控作用奠定了基础。最后总结了肠道菌群可以作为一个预防和治疗肥胖的有效靶点,可以通过在食物中添加有益菌或者通过菌群移植来治疗肥胖。     

Childhood obesity,is fast food exposure a factor?

Access to fast food has often been blamed for the rise in obesity which in turn has motivated policies to curb the spread of fast food. However, robust evidence in this area is scarce, particularly using data outside of the US. It is difficult to estimate a causal effect of fast food given spatial sorting and ever-present exposure. We investigate whether the residential access to fast food increased BMI of adolescents at a time when fast food restaurants started to open in the UK. The time period presents the study with large spatial and temporal differences in exposure as well as plausibly exogenous variation. We merge data on the location and timing of the first openings of all fast food outlets in the UK from 1968−1986, with data on objectively measured BMI from the 1970 British Cohort Survey. The relationship between adolescent BMI and the distance from the respondents’ homes and time since opening, is studied using OLS and Instrumental Variables regression. We find that fast food exposure had no effect on BMI. Extensive robustness checks do not change our conclusion.     

Genetics of obesity

Considerable attention is currently being paid to the secular changes in food intake and physical activity that underlie the increase in the prevalence of obesity that is apparent in many societies. While this is laudable it would be unwise to view these environmental factors in isolation from the biological factors that normally control body weight and composition and the compelling evidence that inter-individual differences in susceptibility to obesity have strong genetic determinants. This is particularly important, as it is only in the past decade that we have begun to obtain substantive information regarding the molecular constituents of pathways controlling mammalian energy balance and therefore, for the first time, are in a position to achieve a better mechanistic understanding of this disease. Population-based association and linkage studies have highlighted a number of loci at which genetic variation is associated with obesity and related phenotypes and the identification and characterization of monogenic obesity syndromes has been particularly fruitful. While there is widespread acceptance that hereditary factors might predispose to human obesity, it is frequently assumed that such factors would influence metabolic rate or the selective partitioning of excess calories into fat. However, it is notable that, thus far, all monogenic defects causing human obesity actually disrupt hypothalamic pathways and have a profound effect on satiety and food intake. To conclude, the evidence we have to date suggests that the major impact of genes on human obesity is just as likely (or perhaps more likely) to directly impact on hunger, satiety and food intake rather than metabolic rate or nutrient partitioning. At the risk of oversimplification, it seems that from an aetiological/genetic standpoint, human obesity appears less a metabolic than a neuro-behavioural disease.     

Examining the temporal relationships between childhood obesity and asthma

Childhood obesity has become an issue of increasing concern to health researchers and policymakers in the United States. One important chronic health condition linked to obesity is pediatric asthma. Although researchers have speculated that both conditions may have common origins, the majority of research in this area has focused on a unidirectional relationship between obesity and later asthma. However, much of the literature is limited by its reliance on cross-sectional data and its failure to examine the possibility that asthma may influence weight fluctuations through changes in physical and sedentary activity. Using data from the Early Childhood Longitudinal Study-Kindergarten Cohort (ECLS-K), I explore the bidirectional relationships between childhood obesity and asthma. The results in this paper suggest that past asthma levels are positively correlated with changes in BMI and the onset of obesity. However, only new onset asthma is positively correlated with subsequent changes in BMI. The potential mechanisms are unclear, as I find little evidence that asthma is structurally related to changes in physical or sedentary activity over time. When testing the prevailing hypothesis that obesity is related to subsequent asthma, I find that lagged weight status is strongly related to asthma prevalence levels but that the onset of overweight or obesity is not associated with the subsequent onset of asthma. These results suggest that the onset of asthma may be related to subsequent weight gain over time.     

Dynamic macroecology on ecological time-scales

Aim The discipline of macroecology is increasingly being regarded as an effective vehicle for the evaluation of recent population‐ to ecosystem‐level responses to widespread human and environmental influences. However, due to the prevalent use of time‐averaged and cumulative data in macroecological analyses, the majority of the patterns that emerge from research in this field can be regarded as static. Here we review the application of dynamic macroecological analyses to changes in relationships between macroecological variables on seasonal to decadal scales. We illustrate the strength of this perspective for documenting changing patterns and testing hypotheses related to these dynamics on ecological time‐scales. Location Studies were compiled and reviewed from terrestrial and aquatic ecosystems. Methods We review examples of temporal changes in macroecological patterns driven by recent anthropogenic influences and environmental change. Results The dynamic nature of macroecological patterns on ecological time‐scales has been revealed in recent years across a wide range of ecosystems, largely through the development, maintenance and analysis of biotic and environmental monitoring time series. The resultant analyses complement examinations of dynamics over evolutionary time and have similarly revealed that static portrayals can conceal important temporal dynamics that underlie the patterns of interest. As a consequence, static depictions, resting as they do on comparative analyses in which the validity of space‐for‐time substitutions is assumed, may be of limited use for testing hypotheses related to the mechanisms underlying the patterns revealed and, by extension, the development of reliable predictions of future states. Main conclusions Recent dynamic macroecological analyses have demonstrated the utility of combined spatial and temporal replication, and have contributed to hypothesis testing related to the mechanistic processes underlying changes in macroecological patterns on ecological time‐scales. We suggest four specific avenues of future research to further the development and application of temporal approaches on similar time‐scales within the field of macroecology.     

人Leptin和肥胖的研究进展

肥胖已经成为一种社会现象,其发病过程复杂,危害严重。近年来的研究表明,肥胖是一种由食欲和能量调节紊乱引起的疾病,与遗传、环境、膳食结构等多种因素有关,其中基因是主要的决定因素。最近人和小鼠的肥胖基因被相继克隆,发现它能在脂肪组织特异表达,其编码的蛋白Leptin可作用于下丘脑,产生抑制摄食、减轻肥胖、减少体重的作用。此外,它还对生殖系统、造血系统等有调节作用。     

A simple imputation method for longitudinal studies with non-ignorable non-responses

Missing data are a common problem in longitudinal studies in the health sciences. Motivated by data from the Muscatine Coronary Risk Factor (MCRF) study, a longitudinal study of obesity, we propose a simple imputation method for handling non-ignorable non-responses (i.e., when non-response is related to the specific values that should have been obtained) in longitudinal studies with either discrete or continuous outcomes. In the proposed approach, two regression models are specified; one for the marginal mean of the response, the other for the conditional mean of the response given non-response patterns. Statistical inference for the model parameters is based on the generalized estimating equations (GEE) approach. An appealing feature of the proposed method is that it can be readily implemented using existing, widely-available statistical software. The method is illustrated using longitudinal data on obesity from the MCRF study.     

The hypothalamic syndrome in rats.

The original conception of the hypothalamus controlling feeding by the activity of two specific and reciprocally inhibitory centers has now been largely abandoned. Detailed neural research using a wide variety of methods has demonstrated the complex morphological and functional organization of this part of the brain and has modified the earlier simplistic approach. However, examination of the feeding responses to a variety of stimuli that represent components of control of feeding indicates that much or even most feeding control is extrahypothalamic. As demonstrated by the obesity or aphagia resulting from hypothalamic damage or from reversible hypothalamic interference, the hypothalamus influences or modulates feeding control, possibly by an enabling action, but it does not itself substantially control food intake either in the short or the long term. In the cachaxia of cancer, which can tentatively be regarded as a negative obesity, and which is closely reproducible in a rat model, the decline of food intake can be attributed to failure of control components that are all extrahypothalamic, and the deterioration of control of feeding appears to be quite independent of the hypothalamus. The very detailed reconstruction of intrahypothalamic circuitry that has been developed in recent years has not yet had any real impact on the problem of where or how the active control of food intake is generated or the way in which the hypothalamus influences this control.     

The Long‐Term Management of Obesity with Continuing Pharmacotherapy

Objective: Long‐term, possibly lifetime, use of medications for the management of obesity may be thought to be similar to the use of pharmacotherapy for other chronic diseases such as hypertension or diabetes. Because there have been no systematic studies of this extended use, the experience of eight patients who have used obesity medications in a sustaining manner was studied. Research Methods and Procedures: The clinical characteristics of eight adult patients, each of whom has experience with long‐term (more than 10 years) use of medications for weight loss and weight maintenance, were studied. Results: The clinical experience of these eight patients was analyzed. Each chose to sustain the use of weight management medications for more than 10 years because of perceived benefit, comfort, and the absence of significant side effects. There has been no evidence of the development of tolerance, addiction, or misuse and no adverse events related to the medication. The beneficial effects of the medication have not diminished with time. Discussion: The clinical characteristics of eight patients, each of whom has used obesity pharmacotherapy for more than 10 years, are described. The experience of these eight individuals cannot be generalized to the entire population of overweight or obese patients. It does suggest, however, that some patients respond successfully to this form of therapy and that they will derive value from it for the management of this disease. Efforts should be made to identify these patients, and consideration should be given to the use of chronic medications for the continuing management of obesity.