Program ENERGY's goal is to reduce obesity/type 2 diabetes in suburban/rural elementary school children and families by teaching/reinforcing body science, energy balance and healthy behavior choices. A specific extension focusing on brain and nervous system science and good decision‐making was delivered to three classes of 6th grade children at Tavelli Elementary School in Ft. Collins, CO. An 8‐week program of classroom explorations and outdoors activities on the brain, body image, mental illness and their impact on behavioral intent was delivered by scientists. Beginning and end of intervention assessments including knowledge and attitudes about brain and nervous system science were conducted. Results show statistically significant improvements in: health and science knowledge (brain science), attitudes (mental illness), behaviors (sensory physiology, increased body acceptance), and increased interest in science/health‐related careers. Total score (n=57) was 24% ± 4% for the pre test and 60% ± 4% for the post test (t=13, p<0.05). The intervention had high rates of enrollment and retention, positive evaluations by children and educators, and produced significant positive outcomes. Thus, this extension of Program ENERGY into explorations, guided by scientists, of brain and nervous system science and behavior was effective and could be replicated in other schools. Supported by NCRR, SEPA, NIH grant.

Program ENERGY (PE) is a science/health-inquiry learning enrichment program combining classroom (body science, health, nutrition) and physical activities designed to prevent obesity and type 2 diabetes. Participants are children in grades 2–6 in suburban/rural public schools with high Hispanic or/and low income enrollments. PE was disseminated to more than 800 children in 40 classrooms in 3 states (CO, TX, and WV) in 2005–2006. Effectiveness was evaluated by pre/post-assessments (beginning and end of school year).

A new framework for understanding the control of feeding behavior, with special emphasis on the evolution of hunger, the initiation of feeding, and its dependence on patterns of blood glucose, is the subject of this review. A perspective on the current status and future directions of this search for a more complete understanding of the regulation of feeding behavior in laboratory rats and humans is presented including theoretical and experimental components. First, a historical perspective on the role of blood glucose in the control of feeding is presented. Next, the theoretical approaches that have been applied to the control of feeding and had a strong influence on experimental feeding research are summarized. This is followed by a statement and overview of a current theory that has emerged from studies of the role of transient declines in blood glucose in the control of meal initiation. The current working hypothesis that transient declines in blood glucose are endogenous metabolic patterns that are detected and recognized by the central nervous system and are mapped into meal initiation in rats and are correlated with meal requests in humans are then presented. Then, the experimental studies on meal initiation and its dependence on patterns of blood glucose, first in rats and then in humans, are reviewed in detail. Finally, the future directions of the work, limitations, and the implications for the understanding of the control of feeding behavior and the regulation of energy balance are discussed.

To assess the biological activity and tolerability of pegylated recombinant native human leptin (PEG-OB), 30 obese men (mean body mass index, 33.9 kg/m2) were randomized to a double-blind treatment with weekly sc injections of 20 mg PEG-OB or placebo for 12 weeks, in addition to a hypocaloric diet (deficit, 2 MJ/day). Body composition, energy expenditure, and metabolic parameters were measured before and after treatment. PEG-OB was generally well tolerated based on adverse event reports, lab values, and vital signs. Weekly sc PEG-OB led to sustained serum concentrations of PEG-OB and leptin throughout treatment. No significant differences in the delta or percent weight loss, percent body fat, sleeping metabolic rate, or respiratory quotient were observed between the PEG-OB and placebo groups. Percent change in serum triglycerides from baseline was significantly correlated with body weight loss in the PEG-OB group, but not in the placebo group. Although larger reductions in serum triglycerides were observed in the PEG-OB group compared with the placebo group, these differences were not statistically significant. We concluded that weekly injection of PEG-OB leads to sustained serum concentration of PEG-OB and leptin throughout the 12-week treatment period and is generally well tolerated. The trends observed in serum triglycerides suggest that a weekly 20-mg sc treatment with PEG-OB may have biological effects in obese men.

Obesity is a complex, increasingly prevalent, and important health problem throughout the world. Human obesity is characterized by increased adipose tissue mass resulting from a complex interaction of genetic predisposition to metabolic efficiency and environmental/lifestyle factors. Recent studies have clearly demonstrated that obesity is a disease with a strong biological basis. Although treatment (e.g., healthy eating (including behavioral modification), physical activity, drugs) is available and most people can achieve medically significant weight loss (5%-10% of initial body weight), the long-term maintenance of that weight loss and its associated improvement in health is, unfortunately, very rare. However, an explosion of new scientific information concerning the regulation of energy balance and fat mass at several levels has occurred since the discovery of OB protein (also known as leptin). The recent identification of obesity-associated genes and gene products in mice and humans has provided new pathways involved in obesity. This new understanding of the regulation of energy balance has revealed, and will continue to reveal, additional targets for pharmacological intervention that will certainly lead, with a little luck, to innovative medicines to treat obesity. New drugs will be viewed as adjuncts to behavioral and lifestyle change to maintain weight loss and its associated increases in metabolic fitness.

Obesity is an extremely challenging medical condition because it is a multifactorial disease that lies at the interface between the biology of body energy regulation and an environment (physical and sensory) that has been increasingly characterized as 'hostile to good health'. The deceptively straightforward anthropomorphic definition of obesity is the excessive accumulation of body fat. However, obesity is a chronic disease that is much more than excessive fat. It involves genetic predisposition and metabolic, hormonal and behavioural aspects and results in significant morbidity, reduced quality of life, discrimination and early mortality. The development and maintenance of obesity can be considered to result from the integration, or the accumulation, of small daily errors in energy balance over several months and years. The biological factors involved increase the predisposition toward the expansion of adipose tissue mass together with the consequences of an environment that promotes increased food intake and decreased physical activity. Multiple aetiologies may result in similar degrees of obesity.

Obesity is an increasingly prevalent and important health problem. Although treatment is available, the long-term maintenance of medically significant weight loss (5 to 10 percent of initial body weight) is rare. Since 1995 there has been an explosion of research focused on the regulation of energy balance and fat mass. Characterization of obesity-associated gene products has revealed new biochemical pathways and molecular targets for pharmacological intervention that will likely lead to new treatments. Ideally, these treatments will be viewed as adjuncts to behavioral and lifestyle changes aimed at maintenance of weight loss and improved health.

Specific [125I]leptin receptor binding sites have been identified in choroid plexus (CP), but have eluded regional localization within the brain parenchyma. To optimize specific [125I]leptin binding in brain loci, we ran experiments varying the pH of incubation buffers. We found that specific [125I]leptin binding in CP was strikingly pH dependent with the most acidic buffer, pH 5.5, resulting in a greater than 100% increase over the amount of specific binding measured at pH 7.5. While low pH permitted detection of specific binding in parenchymal loci, clear pH dependency was only observed in the CP. In the caudate putamen (CauP), a locus with low specific binding, values for specific binding did not differ significantly across the range of pH conditions tested. Using incubation buffers at pH 6.0 in subsequent binding experiments, we localized specific [125I]leptin binding in several brain loci including thalamus and hypothalamus. In CP and thalamus, where the range of OD permitted analysis of binding parameters, [125I]leptin binding was saturable with increasing concentrations of unlabelled leptin. In all loci, specific [125I]leptin binding was insensitive to competition by high concentrations of other unlabelled compounds. Our results varying pH conditions of the incubation buffer suggest leptin receptors may be divided into subclassifications based on pH sensitivity of the specific binding. Furthermore, our results suggest that although densities are low, high affinity leptin receptors are present in neural loci implicated in food intake and energy balance, and are more widespread in the forebrain than previously determined.

The genes encoding the mature forms of mouse (mOB) and human OB (hOB) protein (also called leptin) were fused to the secretion signal coding sequence of theEscherichia coliouter membrane protein A (sOMP A). The hybrid genes were preceded by a ribosome binding site (RBS) and were expressed under transcriptional control of both the lipoprotein promoter (Plpp) and thelacpromoter-operator (POlac). The recombinant fusion proteins were efficiently expressed and exported into the periplasmic compartment ofE. colicells from where they were recovered by osmotic shock as soluble mature polypeptides with the sOMP A precisely removed. Recombinant mOB and hOB proteins were also produced inSf9insect cells using the baculovirus expression system. Milligram quantities of both proteins were purified to homogeneity using ion-exchange, hydrophobic interaction chromatography and gel filtration and were found to be biologically active and to have antiobesity effects upon testing in genetically obeseob/obmice.

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OB protein (also known as leptin), a previously unknown hormone, is secreted from adipose tissue, circulates in the blood in free and bound forms, enters the brain, binds to a receptor, OB-R, and acts on central neural networks that regulate ingestive behavior and energy balance. The circulating concentrations of OB protein are proportional to adiposity and increase with increasing levels of body fat. OB protein provides a hormonal communication link from fat tissue to the brain. Rapidly accumulating evidence suggests that OB protein appears to play a major role in the control of body fat stores through coordinated regulation of feeding behavior, metabolism, autonomic nervous system and body energy balance in rodents, primates and humans. In less than 2.5 years, research has moved quickly from cloning of the ob gene to demonstration of complex regulation of ob gene expression in adipose tissue in rats and humans, the demonstration of biological activity of OB protein, and the identification of the OB-R receptor. Significant milestones were our demonstration that central administration of on protein leads to reductions in food intake, body weight and alterations in metabolism consistent with activation of the autonomic nervous system and the cloning of the OB-R. The OB-R exists in multiple forms and was found to be expressed in the choroid plexus, the hypothalamus, and several peripheral tissues. OB-R, the long form of OB-R, has the complete intracellular domain and is thought to be the form that signals and mediates the biological effects of OB protein. Evidence has been provided for a specific transport system for OB protein at the blood-brain barrier in mice, rats and humans. The rate of transport is decreased in subjects with high plasma concentrations of OB protein. Thus, reduced entry of OB protein to the brain may be one of the mechanisms of reduced sensitivity of the DR protein pathway in obese individuals. OB protein also appears to play a role in the important neuroendocrine adaptive responses to fasting and in the control of reproduction.