Obesity and homestasis Write a five page (body; double spaced) review of the top

Question

Obesity and homestasis Write a five page (body; double spaced) review of the topic from a public health biology perspective. In your review, include the following: Discuss the biological basis of energy homeostasis, including an introduction to your chosen focus area; Discuss some of the recent (within five years) and current research on the focus area you chose, including study aim, methods, and results of the studies you discuss; Explain the value and application of the above research findings to public health, citing the studies as needed, and providing some examples of how this information is or can be used in public health policy, programs, and practice. Your paper must provide APA-formatted references for all resources used and adhere to APA style and format. APA style headers will be expected for the three subsections of biological basis, research, and public health application. Use subheaders as needed. A title page and a reference page is required. An abstract is optional. Use your APA manual,

Explanation / Answer

ABSTRACT Obesity represents one of the most urgent global health threats as well as one of the leading causes of death throughout industrialized nations. Efficacious and safe therapies remain at large. Attempts to decrease fat mass via pharmacological reduction of energy intake have had limited potency or intolerable side effects. Increasingly widespread sedentary lifestyle is often cited as a major contributor to the increasing prevalence of obesity. Moreover, low levels of spontaneous physical activity (SPA) are a major predictor of fat mass accumulation during overfeeding in humans, pointing to a substantial role for SPA in the control of energy balance. Despite this, very little is known about the molecular mechanisms by which SPA is regulated. The overview will attempt to summarize available information on neuroendocrine factors regulating SPA. KEY WORDS: • ghrelin • physical activity • energy expenditure • AGRP • NPY • CART • leptin Obesity: a serious nationwide health problem The United States is the epicenter of an ongoing obesity pandemic (1,2). Rates of obesity and its associated comorbidities are rising steadily in both adults and children in the majority of the developed and developing world (3–5). This makes obesity an escalating public health crisis that requires scientific and public health attention (6). The obesity rates are rising despite increased public awareness and increasing attention from governments highlighting the need for effective therapeutic strategies. Currently, 61% of the U.S. population is overweight or obese and therefore at increased risk for a number of diseases that are associated with increased body fat (1,7). Indeed, the obesity epidemic has already resulted in dramatic increases in type-2 diabetes, particularly among younger populations (5). Increased body fat also increases the risk for cancer (8). As a result, the future of the health of the U.S. population depends critically on identifying and providing the best treatment and prevention strategies for obesity in the years ahead (9). To date, however, few treatments provide safe and efficacious weight loss that can be sustained over long periods of time (10). Low physical activity level as one cause for the increasing prevalence of obesity Body fat fluctuates with the difference between energy intake and energy expenditure over time (11,12). Thus, understanding the regulation of energy balance can be partitioned into understanding the factors that regulate both energy intake and energy expenditure (13–15). Whereas the neuroendocrine control of energy intake has received intense scrutiny over the past decade, much less attention has been paid to the control of energy expenditure. Nevertheless, a compelling case can be made that obesity is often associated with lowered rates of energy expenditure (16). A large body of published evidence has documented, for example, a strong link between time spent watching television or working at a computer with obesity in both children and adults (17–21). Unfortunately, despite the apparent importance of energy expenditure for body weight regulation, our understanding of the components that regulate energy expenditure is less developed (22) (Fig. 1). View larger version (81K): In this window In a new window FIGURE 1 Energy expenditure can be partitioned into 3 basic categories: BMR, the thermic effect of food, and SPA. These categories can be assessed with the help of, i.e., an indirect calorimeter. Because caged laboratory rodents do not exercise voluntarily in the way that humans do, SPA in rodents is typically defined as all physical activity occurring within a single-housed cage situation that is above BMR and the TEF. Defined this way, SPA is independent of its specific character (running, grooming, climbing, fidgeting, feeding, sniffing, rearing, drinking, etc.). A substantial change in ongoing SPA will therefore be reflected as a substantial change in energy expenditure as measured by indirect calorimetry (22,37,40). Spontaneous physical activity-induced energy expenditure as an individual determinant of body fat mass Humans show considerable interindividual variation in susceptibility to weight gain in response to overeating. The physiological basis of this variation was recently investigated (23) by measuring changes in energy storage and expenditure in nonobese volunteers who were fed in excess of weight-maintenance requirements. Not surprisingly, as energy intake exceeds energy expenditure and body fat accumulates, the system responds by increasing energy expenditure. That is, the system compensates through changes of energy expenditure when energy intake is no longer under voluntary control. Importantly, two-thirds of the increase in total daily energy expenditure in this situation was attributable to increased spontaneous physical activity (SPA).3 In fact, changes in SPA directly predicted resistance to fat gain with overfeeding on a hypercaloric diet. These results point to SPA as a labile component of total energy expenditure that is a key tool of the homeostatic system that maintains relatively constant body fat over time (23). Moreover, these results indicate that differences in the ability to recruit SPA in the face of positive energy balance are not only predictive but also critical to the large differences among individuals in their response to positive energy balance and the maintenance of body fat (24,25). Particularly relevant to human obesity is the phenomenon of nonconscious, nonexercise activity thermogenesis (NEAT), a variable that relates to SPA in rodents. NEAT is defined as the energy expended for everything we do that is not sleeping, eating, or sports-like exercise (22). It ranges from the energy expended walking to work, typing, performing yard work, undertaking agricultural tasks, and fidgeting. Even trivial physical activities can increase metabolic rate substantially and it is the cumulative impact of a multitude of such exothermic actions that culminate in an individual’s daily NEAT (25). It is, therefore, not surprising that NEAT is used to explain the majority of an individual’s nonresting energy needs. Epidemiological studies highlight the importance of culture in promoting and/or quashing NEAT (26). Agricultural and manual workers have high NEAT, whereas wealth and industrialization appear to decrease NEAT (27,28). Physiological studies demonstrate that NEAT fluctuates with changes in energy balance; specifically, NEAT increases with overfeeding and decreases with underfeeding (29). Thus, NEAT could be a critical component in how we maintain our body weight and/or develop obesity or lose weight (24). When humans overeat, activation of SPA can dissipate excess energy and help preserve leanness, and failure to activate SPA may result in susceptibility to gain fat (22,24). Although the lack of sufficient physical activity has clearly been recognized as one of the major correlates for the rapidly increasing prevalence of obesity, countermeasures are mostly limited to educational recommendations. Although most obese individuals are well informed about such recommendations, the combination of genetic predispositions with the environmental challenges of abundant high-energy food, tempting sedentary lifestyles, and increasingly stressful and time-consuming professional occupation often conspire to make a sufficient and chronic increase in physical activity impossible (30–32). Although physical activity is the most variable and easily altered component of total energy expenditure, conscious efforts to increase physical activity must be considered unsuccessful on an epidemic level, even given the strong desire to lose weight and the accompanying and consequent high level of suffering in most obese individuals (3,33). An efficient anti-obesity drug is needed, and a pharmacological increase of SPA may be one option that should be investigated as one component of a future drug treatment strategy for obesity. The WHO, NIH, and the Surgeon General of the United States have all stated that increasing physical activity is a priority for obesity prevention and treatment. The WHO specifically recommends strategies that augment nonexercise activity and thereby increase energy expenditure by 834 kJ/d (200 kcal/d). For the average obese subject, 834 kJ/d is the equivalent to fidgeting-like activity of 2.5 h/d or a strolling-equivalent activity (1.6–3.2 km/h) of 1 h/d (34). Mechanisms regulating SPA: lessons from rodent models Gaining a better understanding of the biological determinants involved in the regulation of SPA is essential because, as outlined above, reduced energy expenditure (NEAT) associated with decreased SPA is thought to be a major underlying factor in the increasing prevalence of obesity. To facilitate interpretation in humans, it is helpful to consider evidence from interventional and less descriptive studies in animal models. In rodent models, energy intake is frequently not the major determinant of body fat mass. A better understanding of the biological determinants involved in the regulation of SPA from experiments in animal models will have important and beneficial implications for the development of strategies for the prevention of weight gain leading to obesity and subsequent morbidity and mortality in the human population. In addition to its favorable effects on energy balance and fat mass, increased SPA might also have a direct positive influence on glucose metabolism (35,36). To understand the molecular mechanisms regulating SPA, it is mandatory to explicitly define and consequently dissect its physiological and behavioral components. As discussed above, total energy expenditure is composed of basal metabolic rate (BMR), the thermic effect of food (TEF), and physical activity (Fig. 1) (37). One model provides a new environment for rodents by placing them in an open field, thus eliciting increased exploratory activity (influenced by both motivational and behavioral components) (38). Another model allows the nonvolitional activity or SPA of an adapted rodent housed in a single cage and includes ambulatory and climbing movements as well as rearing and fidgeting and food intake–and drinking-associated activity (39). Scientific understanding of the regulation of SPA is severely incomplete. Some authors argue that the predominant direction of influence goes from body weight to compensatory activity (40), whereas others argue that changes in activity are responsible for changes in body weight (22). Several relatively extensive and detailed reports have documented an influence of diet, rodent strain, gender, age, or hypothalamic lesions on the level of SPA in rodents (40). Diet has been suggested as one determinant of SPA based on the observation of hyperactivity in food-deprived animals. However, no solid evidence could be found to generalize this hypothesis, particularly because diet does not explain reduced activity in DIO rodents (40). SPA does seem to be a function of the specific rodent strain examined because there are considerable differences in SPA among, for example, ob/ob mice, New Zealand obese mice, and Zucker fatty (fa/fa) rats and between C57B mice (average SPA) and BALB/c mice (rel. high SPA) or 129sv mice (40,41). An age-related decrease in SPA has been reported (42), as well as a higher average SPA level in female rats and mice relative to males (43). This difference varies with the estrus cycle and has been suggested to be partially due to changes in circulating concentrations of estrogen based on studies in ovariectomized rats (44). Lesions of the ventromedial hypothalamus (VMH) increase food intake and body weight, but also reduce SPA (45). Interestingly, rats with lesions of the paraventricular nucleus of the hypothalamus (PVN) develop an obese phenotype very similar to the one observed in VMH-lesioned animals, but they do not exhibit reduced SPA (46). Although these findings are collectively suggestive with respect to the lack of physical activity contributing to human obesity, not all findings in rodents will be relevant for the understanding of the causes, molecular mechanisms, and treatment modalities of human obesity (40). That said, SPA and its contribution to energy expenditure are difficult to measure in humans. Furthermore, the multiple environmental and voluntary influences on energy expenditure are difficult to control in humans. For one thing, humans are conscious of the benefits of physical activity, and this can bias the outcome of experiments. At another level, studies of hypothalamic neuropeptide action or expression cannot easily be performed in humans. Rodent models therefore provide several advantages for the investigation of the molecular mechanisms controlling the level of SPA. Neuroendocrine regulation of energy balance Energy balance is achieved when energy intake (ingestion and absorption of calories) equals energy output (energy expenditure, thermogenesis). Based on more than half a century of research on the regulation of food intake and energy expenditure in rodents and humans, but most importantly triggered by the discovery of leptin in 1994, the complex current model for the neuroendocrine regulation of energy balance has emerged. Based on this model, afferent signals continuously inform central nervous circuits about acute and chronic changes in energy homeostasis, which in turn integrate this information and respond with efferent signals to immediately initiate the respective adaptive changes and regain energy balance (11,13–15,47–57) (Fig. 2). View larger version (66K): In this window In a new window FIGURE 2 Myriad peripheral signals (including many hormones) are continuously providing central circuits with information about ongoing energy balance and metabolic homeostasis. Specific areas of the brain that have been identified as important for processing this afferent information as well as for the continuous adjustment of an appropriate efferent response are depicted in this figure and discussed in this review article. These areas include the nucleus of the solitary tract (NTS), the lateral parabrachial nucleus (LPB), and other areas in the brainstem region, as well as the arcuate nucleus (ARC), the VMH, the dorsomedial hypothalamus (DMH), the PVN, and the lateral hypothalamus (LH). Communication among these neuronal circuits relies on the generation and release of specific neurotransmitters and neuropeptides. Although expression of the potently orexigenic AGRP is strictly limited to the ARC, the similarly strong appetite-promoting NPY is expressed in numerous regions of the brain including areas involved in the regulation of body weight. The exact anatomical and functional blueprint of the projections among these other neuropeptides and neurotransmitters regulating energy homeostasis [such as CART, MCH, thyrotropin releasing hormone (TRH), corticotropin releasing hormone (CRH), oxytocin (OXY), and vasopressin (AVP)] is unknown. Even less known are the influences of visual, olfactory, and circadian inputs, which might in part be mediated through specific neuronal circuits in brain areas such as the suprachiasmatic nucleus (SCN) or the supraventicular zone (SPZ). Based on our preliminary data and scattered published evidence, we propose that specific parts of these neuroendocrine circuits are controlling SPA in addition to regulating food intake. This schematic figure is based on data from Elmquist, Physiol. Behav. 74 (2001) 703–708; Barsh & Schwartz, Nat. Rev. Genet. 3 (2002) 589–600; Ahima & Osei, Trends Mol. Med. 7 (2001) 205–213; Berthoud, Neurosci. Biobehav. Rev. 26 (2002) 393–428; Kalra et al., Endocr. Rev. 20 (1999) 68–100; Saper et al., Neuron 36 (2002) 199–211; Flier, Cell 116 (2004) 337–350. Over the past 3 years, an important new aspect has been added to this view by the discovery of the peptide hormone, ghrelin, which is mainly derived from the stomach, but which is also expressed in the pancreas, duodenum, and hypothalamus (58). Ghrelin administration stimulates food intake and increases body fat mass (59). The only identified ghrelin-responsive receptor, the growth hormone secretagogue receptor (GHS-R1a) (60), is localized in specific neurons of the hypothalamic arcuate nucleus, neurons which coexpress the orexigenic neuropeptide Y (NPY) and agouti-related protein (AGRP) (61,62). Circulating plasma concentrations, as well as gastric mRNA levels of ghrelin, increase with energy restriction or fasting (59) and decrease immediately following food intake in both rodents and humans (59,63,64). Based on these findings, ghrelin has been proposed to represent the only peripheral orexigenic agent and to finally prove the disputed existence of a meal initiation factor (65). Although numerous reports have focused on the orexigenic effects of ghrelin (48,66–68), very few have investigated its effects on energy expenditure (59,69,70), and we believe that the latter can subtantially contribute to a ghrelin-induced increase in fat mass.

Related Questions

Navigate

• Browse (All)
• Browse O
• Subjects

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.