Human Appetite Research Articles

Ghrelin effect on nutritional indices, midgut and fat body of Lymantria dispar L. (Lymantriidae)

Ghrelin is a 28-amino acid peptide that has significant effects on appetite and growth in humans and animals. The aim of this study was to examine 4th instar larvae of the pest insect Lymantria dispar L. after ghrelin treatment. Parameters included changes in nutritional indices (efficiency of conversion of ingested food, efficiency of conversion of digested food, approximate digestibility); midgut and fat body mass; total proteases, trypsin and leucine aminopeptidase activities in the midgut; number, height and width of columnar and goblet cells and their nuclei in the midgut epithelium and detection of ghrelin-like immunoreactivity in the midgut tissue. Four subpicomolar injections of ghrelin (0.3pmol) or physiological saline (control) were applied every 24h. The nutritional indices were higher in the ghrelin treated than in the control group. Ghrelin treatment was also associated with elevation of midgut mass, induced digestive enzyme activities, increased fat body mass and morphometric changes in columnar and goblet cells. This is the first report of the presence of ghrelin-like hormone in endocrine cells of an insect midgut. Such information provides additional evidence for application of this relatively simple model system in the future studies of the mechanisms underlying of digestion and energy balance in more complex organisms.

The Effect of Tesofensine on Appetite Sensations

Tesofensine (TE), an inhibitor of monoamine presynaptic reuptake, has produced twice the weight loss seen with currently marketed drugs. However, its long term effect on appetite in humans has not been studied. A multicentre phase II trial was divided into two parts (24 weeks each). Part 1 had a randomized, double-blind, placebo-controlled design and Part 2, an open-labeled, single-group, uncontrolled design. A drug-free period (12 ± 3 weeks) separated them. In Part 1, participants (n = 158) were assigned to 0.25, 0.5 or 1.0mg TE, or placebo. Completers of Part 1 were invited to participate in Part 2 (n = 113), during which they all received 0.5 or 1.0mg TE. Appetite sensations and a composite satiety score (CSS = satiety + fullness + (100 - hunger) + (100 - prospective food consumption) were assessed. In Part 1 TE induced a dose-dependent increase in CSS at week 12 that correlated with weight loss during the 24 weeks (r = 0.36, P < 0.0001). However, CSS diminished over time as weight loss progressed (e.g., for 1.0mg; 52 ± 17mm; 64 ± 13mm; 55 ± 13mm at baseline, week 12 and week 24, respectively). After drug withdrawal CSS returned to baseline values (50 ± 17mm, in the whole sample.), despite the participants' reduced-weight state (-7.2 ± 6.7kg, P < 0.0001). The reintroduction of TE in Part 2 increased CSS again (56 ± 17mm at week 60), regardless of initial treatment/weight loss. We postulate that enhanced satiety is involved in early weight loss. Whether the attenuated effect on appetite seen after 24 weeks is due to a counteracting effect in the weight reduced state or whether the appetite suppressing effect of TE per se diminishes over time is, however, still unclear.

Wole Soyinka: Dance Master of Appetite

Wole Soyinka is a master of the chameleon. He has shifted shapes so often from poetry to drama to fiction, and from comedy to tragedy and back again, that it is no wonder he has confused and sometimes upset critics and readers. His early work was at times obscure and abstract, but if there is one theme that connects Iiis comedies to Iiis tragedies , it would certainly deal with the enormity and variety of human appetite. Whether it be for power, sex, money, or martyrdom, overwhelming appetite has been one of the constants of Iiis work. We can study its evolution in four of Iiis early plays: two satires-Opera Wonvosi and Kongi Is Han'est, and two tragedies-The Bacchae of Euripides and Death and the King s Horseman.Kongi s Han'est and Opera Wonvosi are both satires of political tyranny. appetite in play is for absolute power in the hands of dictators like those who have dominated so much of post-colonial African history. two tragedies also deal with these appetites for power and control as well as their opposities: the appetites for pleasure, release, sex, and wild ecstasy.Kongi 's Han'est (1065) presents us with a classic parody of an African dictator. Kongi assigns Iiis Aweri lackeys to write Iiis books for him so that he may appear a man of learning and wisdom. His appetite for grandeur is so messianic he wants to renumber the calendar for himself, so that the past will be measured in years B.K.H. (Before Kongi's Harvest). He poses for a photographer in savior-like postires that could be labeled The Face of Benevolence... the Giver of Life (WS 93) Though Iiis enemies try to assassinate him, Kongi survives their attack and maintains Iiis power. final grim reality is that the tyrant still rules and Iiis enemies, who represent the healthy appetites of love and tradition, are killed or must flee for their lives. As in much of recent African history, the excessive appetite for power rules the day.Soyinka 's appetite for satire also leads him to write Opera Wonyosi, Iiis interpretation of a modern European classic: Brecht and Weill's Threepenny Opera (1928). Brecht's play was already an adaptation of Iiis original source, John Gay's Beggars Opera (1728). Both Gay and Brecht were out to criticize political corruption in their own societies: 18th century Britain and early 20th century Germany. two works satirize the human appetites for money, love, and power. In both the main characters are thieves, prostitutes, and hustlers: figures from the underworlds of London and Berlin. In other words, they provide a perfect model for Wole Soyinka.Soyinka keeps Brecht's plot intact but moves it to contemporary West Africa, retelling the story of Mack the Knife, Iiis rival the King of Beggars- called Chief Anikura and Iiis wife De Madam, and Mack's troubles in love with Polly, Lucy, Jenny and other ladies of the night. He even keeps some of Kurt Weill's famous songs, especially the Ballad of Mack the Knife, for which he writes Iiis own lyrics alluding to examples of Nigerian corruption like the marble monopoly at Igbeti. Instead of the street singer, Soyinka updates that role to a hip Dee-Jay. His main addition to Brecht's play is its setting in the neighboring Central African Republic during the coronation of His Imperial Diminuative Emperor Bokassa I. Both Gay and Brecht made use of coronation settings which usually provided major business for thieves and beggars. Gay used the coronation of King George II in 1727 and Brecht used the coronation of Queen Victoria in 1837. But Soyinka actually introduces Emperor Bokassa as one of Iiis major characters. Folksy Boksy as the Dee-Jay calls him. is simply too good a target for satire. His first scene is a masterful comic riff on the blustering tyrant. Emperor Boky compares himself to Napoleon who also started out as a commoner and was not even a real Frenchman coming from Corsica. Boky is a francophonie African, but like Napoleon he is a powerful leader who glorifies the traditions of the French Revolution, at least in Iiis own mind. …

Ghrelin and the central regulation of feeding and energy balance

Ghrelin was discovered in 1999 as growth hormone secretagouge released from the gut. Soon after it was recognized that ghrelin is a fundamental driver of appetite in rodents and humans and that its mode of action requires alteration of hypothalamic circuit function. Here we review aspects of ghrelin's action that revolve around the central nervous system with the goal to highlight these pathways in integrative physiology of metabolism regulation including ghrelin's cross-talk with the action of the adipose hormone, leptin.

Functionality of alginate based supplements for application in human appetite regulation

The present study investigated the functional properties of different alginate solutions intended as dietary supplements for enhanced satiety and limited energy intake in humans. Characteristics of the three alginates, obtained by NMR spectroscopy, showed differences in their mannuronic:guluronic (M:G) acids ratio. By correlation with their rheological behaviour it was found that alginate solutions with low M:G (M:G=0.8) exhibited stronger gel strength than did solutions with higher M:G (1.3 and 2.5). Subsequently, eight subjects participated in an acute meal test, where two alginate-based preloads with different M:G ratios (0.8 and 2.5) were administered after subjects had fasted overnight. Subjective appetite sensation was assessed over 4h; thereafter an ad libitum meal was served. Self-perceived capacity for food intake decreased (P=0.02), fullness increased (P=0.05), and subsequent energy intake decreased numerically by 10% (P=0.1) after consumption of the alginate formulation with low M:G compared with high M:G. These findings suggest that high-guluronic acid alginates are worth further investigation in relation to appetite regulation.

Current progress in the assessment of ‘liking’ vs. ‘wanting’ food in human appetite. Comment on ‘“You Say it’s Liking, I Say it’s Wanting...”. On the difficulty of disentangling food reward in man’

Studies that make use of separate measures to capture ‘liking’ and ‘wanting’ components of food reward signal a paradigm shift in research on hedonic (over)eating in man. In a recent review, Havermans (2011) highlighted some key methodological and theoretical challenges faced by those working on this issue. Unfortunately, this selective reading of the recent literature in the field presents a skewed picture; but it should not dampen the building momentum. On the other hand the paper is a timely call for researchers to clarify some of the neological confusion that has inevitably been generated along the way. In this response to Havermans (2011), we offer a more robust review of current progress in the assessment of ‘liking’ vs. ‘wanting’ food in human appetite. The evidence supports important theoretical and practical implications for a dual-process account of food reward; the developing nature of the research means the majority of these remain tantalisingly unexplored.

Lorcaserin and the Role of 5-HT2C Agonism in the Treatment of Obesity

The serotonin (5-HT) system is implicated in the control of human appetite expression. However, previous serotonergic approaches to obesity, d-fenfluramine and sibutramine, were withdrawn over issues of safety. Selectively targeting hypothalamic 5-HT2C receptors should reduce the side effects produced by previous treatment. Lorcaserin is the first of a new generation of highly selective 5-HT2C agonists to pass through clinical development. Data is limited but the drug produces significant reductions in energy intake. These appear small compared to those reportedly produced by sibutramine and there is little evidence to indicate behavioural specificity or a clear satiety effect. However, Lorcaserin produces significant placebo-subtracted weight loss over two years of treatment which may be greater than current treatments such as the lipase inhibitor orlistat. Drugs that strengthen satiety may help individuals resist the urge to over-consume and maintain the reduction in energy intake required for successful weight control. However, for a number of patients Lorcaserin proved to be ineffective. For a centrally acting agent the drug's effect on appetite and behaviour remain poorly characterised. In summary, Lorcaserin produces statistically significant effects on energy intake, but the clinical significance of these findings is still debatable. Furthermore, the history of serotonin drugs indicates caution is warranted.

Neuroimaging and obesity: current knowledge and future directions.

Neuroimaging is becoming increasingly common in obesity research as investigators try to understand the neurological underpinnings of appetite and body weight in humans. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and magnetic resonance imaging (MRI) studies examining responses to food intake and food cues, dopamine function and brain volume in lean vs. obese individuals are now beginning to coalesce in identifying irregularities in a range of regions implicated in reward (e.g. striatum, orbitofrontal cortex, insula), emotion and memory (e.g. amygdala, hippocampus), homeostatic regulation of intake (e.g. hypothalamus), sensory and motor processing (e.g. insula, precentral gyrus), and cognitive control and attention (e.g. prefrontal cortex, cingulate). Studies of weight change in children and adolescents, and those at high genetic risk for obesity, promise to illuminate causal processes. Studies examining specific eating behaviours (e.g. external eating, emotional eating, dietary restraint) are teaching us about the distinct neural networks that drive components of appetite, and contribute to the phenotype of body weight. Finally, innovative investigations of appetite-related hormones, including studies of abnormalities (e.g. leptin deficiency) and interventions (e.g. leptin replacement, bariatric surgery), are shedding light on the interactive relationship between gut and brain. The dynamic distributed vulnerability model of eating behaviour in obesity that we propose has scientific and practical implications.

The effects of l-arabinose on intestinal sucrase activity: dose-response studies in vitro and in humans

On the basis of results in cell cultures, rodents, and pigs, l-arabinose may inhibit intestinal sucrase activity and thereby delay sucrose digestion. The objective was to investigate the dose-response effects of l-arabinose on intestinal sucrase activity in vitro and glucose tolerance, appetite, and energy intake in humans. In vitro, Caco-2 cells were cultured for 21 d, homogenized, and used as an enzyme preparation with sucrose as substrate in concentrations from 7 to 280 mmol/L with 0.84, 1.4, and 2.8 mmol l-arabinose/L as inhibitor. Released glucose was measured after 30 min. In the human studies, 15 healthy men participated in a randomized, double-blind, crossover study. Sucrose beverages (75 g in 300 mL) supplemented with 0%, 1.3%, 2.7%, and 4% by weight of l-arabinose were tested at breakfast. Blood for the measurement of glucose, insulin, C-peptide, incretin hormones, and triacylglycerol was collected under fasting conditions and for 3 h postprandially. Postprandial appetite sensations and energy intake at lunch were registered. In vitro, the addition of l-arabinose resulted in uncompetitive inhibition of sucrase activity. In the human studies, supplementation with 4% l-arabinose produced an 11% lower glucose peak, a 33% lower and delayed insulin peak, a 23% reduction in the incremental area under the curve (iAUC) for insulin, a 23% lower and delayed C-peptide peak, a 9% reduction in the iAUC for C-peptide, a 53% increase in the iAUC for glucagon-like peptide-1 (GLP-1), and a 28% reduction in the iAUC for glucose-dependent insulinotropic polypeptide. No effects on triacylglycerol, gastrointestinal symptoms, appetite ratings, or energy intake were observed. l-Arabinose inhibits sucrase activity from Caco-2 cells; 4% l-arabinose in sucrose beverages reduces postprandial glucose, insulin, and C-peptide responses and enhances the GLP-1 response in humans without gastrointestinal adverse effects. This trial is registered at clinicaltrials.gov as NCT00302302.

Learning and the motivation to eat: Forebrain circuitry

Appetite and eating are not only controlled by energy needs, but also by extrinsic factors that are not directly related to energy balance. Environmental signals that acquire motivational properties through associative learning—learned cues—can override homeostatic signals and stimulate eating in sated states, or inhibit eating in states of hunger. Such influences are important, as environmental factors are believed to contribute to the increased susceptibility to overeating and the rise in obesity in the developed world. Similarly, environmental and social factors contribute to the onset and maintenance of anorexia nervosa and other eating disorders through interactions with the individual genetic background. Nevertheless, how learning enables environmental signals to control feeding, and the underlying brain mechanisms are poorly understood. We developed two rodent models to study how learned cues are integrated with homeostatic signals within functional forebrain networks, and how these networks are modulated by experience. In one model, a cue previously paired with food when an animal was hungry induces eating in sated rats. In the other model, food-deprived rats inhibit feeding when presented with a cue that signals danger, a tone previously paired with footshocks. Here evidence will be reviewed that the forebrain network formed by the amygdala, lateral hypothalamus and medial prefrontal cortex mediates cue-driven feeding, while a parallel amygdalar circuitry mediates suppression of eating by the fear cue. Findings from the animal models may be relevant for understanding aspects of human appetite and eating, and maladaptive mechanisms that could lead to overeating and anorexia.

Effect of resistant starch in rice on postprandial glucose response and appetite in humans

Effect of resistant starch in rice on postprandial glucose response and appetite in humans

Pulmonary delivery of peptide YY for food intake suppression and reduced body weight gain in rats

Peptide YY (PYY) is an endogenous anorectic gut-secreted peptide that has been shown to suppress appetite in animals and humans, when given by injection. This study tested if needle-free pulmonary delivery of PYY enables food intake suppression and reduced body weight gain in rats. The PYY pharmacokinetics and effects on brain neuropeptide levels were also examined. Rats received single or once-daily 7-day pulmonary administration of saline or PYYs. Food intake and body weight gain were monitored to study the effects of different doses (0.08-0.90 mg/kg) of PYY3-36, PYY1-36 and PYY13-36. Plasma PYY pharmacokinetics were determined via enzyme-linked immunosorbent assay. Changes in orexigenic neuropeptide Y (NPY) and c-Fos protein levels in the hypothalamus arcuate nucleus (ARC) were measured by immunofluorescence microscopy. PYY3-36 caused dose-dependent and 4- to 6-h food intake suppression following pulmonary delivery. At 0.80 mg/kg, the effect was significant with 35.1 ± 5.7 and 19.7 ± 4.2% suppression at 4 and 6 h, respectively. Repeated administration for 7 days reduced cumulative body weight gain by 39.4 ± 11.0%. PYY1-36, but not PYY13-36, was equipotent to PYY3-36 in food intake suppression. The plasma PYY concentration reached its peak at 10 min following pulmonary delivery with 12-14% of bioavailability. Increased c-Fos and reduced NPY expressions were observed in the hypothalamus ARC, consistent with the magnitude of food intake suppression by each of the PYYs. Pulmonary delivery of PYY enabled significant 4- to 6-h food intake suppression via 12-14% of lung absorption and hypothalamic ARC interaction, leading to reduced body weight gain in rats.

Ghrelin for cachexia

Ghrelin, a natural ligand for the growth hormone (GH)-secretagogue receptor, is primarily produced in the stomach. Administration of ghrelin stimulates food intake and GH secretion in both animals and humans. Ghrelin is the only circulating hormone known to stimulate appetite in humans. As GH is an anabolic hormone, protein stores are spared at the expense of fat during conditions of caloric restriction. Ghrelin also inhibits the production of anorectic proinflammatory cytokines. Thus, ghrelin exhibits anti-cachectic actions via both GH-dependent and -independent mechanisms. Several studies are evaluating the efficacy of ghrelin in the treatment of cachexia caused by a variety of diseases, including congestive heart failure, chronic obstructive pulmonary disease, cancer, and end-stage renal disease. These studies will hopefully lead to the development of novel clinical applications for ghrelin in the future. These studies have also facilitated a better understanding of the molecular basis of the anti-catabolic effects of ghrelin. This review summarizes the recent advances in this area of research.

Salvaging Wilderness from the Tomb of History: A Response to The National Parks: America's Best Idea

In the age of industrialism, wilderness is the counterbalance to human excesses and the inspiration for environmental activists. Today, wilderness is even more important and contested as people face multiple environmental crises on a planet with an exploding human population and voracious consumer appetite. Too often obscured by the technosphere that engulfs us, wilderness awaits its ecoteur filmmakers to give it greater presence on the public screens of the technoscape. After The National Parks: America's Best Idea, wilderness still waits. By treating wilderness as an historical relic and vacation spot, the film saps it of its vital relevance and political power. Audiences must understand the foundational role of wilderness in their lives, instead of being pacified with an history drained of color that disconnects them from wilderness. As people wonder if there is a future for industrial civilization, wilderness provides the last best hope for rethinking our place on earth.

Short term effects of alcohol on appetite in humans. Effects of context and restrained eating

The present study examined further the short-term effects of alcohol on food intake and appetite in women volunteers, testing the extent to which the apparent appetizing effects of alcohol depend on (a) expectations that alcohol had been consumed and (b) disinhibition of dietary restraint. Twenty restrained and 20 unrestrained women consumed a drink preload 30 min before a test meal on four different days, with preloads varying in alcohol content (alcohol or energy-matched control) and drink context (alcohol-related – beer or alcohol unrelated – juice). Significantly more energy was consumed following alcohol than no-alcohol, but this effect depended on the drink consumed: least was eaten after the alcohol-free juice drink, and most after the same juice drink with added alcohol. There was no evidence that the effect of alcohol on intake was due to disinhibition of restrained eating, nor did alcohol increase liking for the test foods. The change in energy intake at lunch was mainly due to greater intake of energy-rich foods on days when alcohol had been consumed. Alcohol also increased rated appetite once food had been tasted, suggesting alcohol may increase food-related reward. Overall these data suggest that effects of alcoholic drinks represent a complex interaction between physiological effects of alcohol and expectations and associations generated by past experience of alcoholic drinks.

Measure for Measure (review)

Reviewed by: Measure for Measure Katharine Goodland Measure for Measure Presented by Theatre for a New Audience at The Duke on 42nd Street, New York, New York. February 6–March 14, 2010. Directed by Arin Arbus. Set by Peter Ksander. Costumes by David Zinn. Lighting by Marcus Doshi. Sound by Jane Shaw. Music by Sarah Pickett. With Jefferson Mays (Duke Vincentio), Robert Langdon Lloyd (Escalus), Rocco Sisto (Angelo), Joe Forbrich (Justice, Barnardine), Alfredo Narciso (Lucio), Elisabeth Waterston (Isabella), John Keating (Pompey), Mary Testa (Mistress Overdone), Samara Bay (Kate Keepdown), LeRoy McClain (Claudio), Graham Winton (Provost), Rose Seccareccia (Juliet, Punk), Denis Butkis (Friar Peter, Froth), Alyssa Bresnahan (Francisca, Mariana, Punk), and John Christopher Jones (Elbow, Abhorson) Arin Arbus’s production of Measure for Measure for Theatre for a New Audience had many of the signature qualities of her definitive 2009 production of Othello: simplicity of design, an eloquent use of theatrical space, and fluid staging that was sensitive to the dramatic tension inherent in specific scenes while at the same time cognizant of the play’s larger motifs and paradoxes. There is a spaciousness and stillness at the core of her productions which allows the text, the players, and the theatrical space to breathe and come to life with apparent effortlessness. The set design consisted primarily of three enormous doors along the upstage wall. Slight changes of lighting altered the doors’ aspects to shift the scene among the play’s three primary locales: the interior of the formal entrance to the Duke’s and Angelo’s offices, the interior of the prison, and the exterior world of the street. The stage itself remained largely bare: a desk was added to signify Angelo’s office; Claudio was granted a chair, center stage, for his prison cell. The cumulative effect of this shared space, altered in perspective by shifts in light, was to embody the play’s investigation of the sometimes tenuous line between virtue and vice, as scenes involving the underworld, or “Southwark,” characters followed hard upon those of the “virtuous” ones. Most memorable was Pompey’s arrest for pimping in 3.2. As Elbow entered at the top of the scene, declaring, “Nay, if there be no remedy for it but that you will needs buy and sell men and women like beasts, we shall have all the world drink brown and white bastard,” Pompey was interrogated by the Duke in the same spot that the Duke and Isabella had stood only moments before as they plotted what, in a certain light, could be seen as the “pimping” of Mariana. Arbus used the upstage balcony to emphasize these parallels and paradoxes: the Duke spied on Claudio’s and Isabella’s prison exchange [End Page 383] from this location; this was Mariana’s “moated grange”; and it served as Angelo’s garden where the bed trick occurred. In the final scene, the set’s three doors served as a symbolic frame for the play’s exploration of the fine line between marriage and prostitution. As Duke Vincentio meted out his “punishments” of marriage, each of the three central pairs completed their coupling by standing framed in the doorways—Claudio and Juliet in the center, Angelo and Mariana stage right, and Lucio and Kate Keepdown stage left. Inviting us to contemplate the similarities and differences amongst the three couples, this concluding tableau aptly symbolized the play’s complex and dark exploration of human appetite, memorialized most succinctly in Claudio’s observation that, “Our natures do pursue, / Like rats that ravin down their proper bane, / A thirsty evil, and when we drink, we die.” Like the set, the contemporary costumes were efficient and understated. The play began with a nod to its Renaissance roots with the Duke appearing in his ducal robes and crown, which he doffed as he made his abrupt departure. From this point on, the costumes were contemporary: dark gray suits for the Duke, Angelo, and Lucio, street clothes for Claudio (jeans and a t-shirt) and Juliet (a dress that accentuated her pregnancy), and fishnets, high heels, mini skirts and skimpy tops for the “bawds.” The middle-aged Mistress Overdone wore a longer dress than the younger women, but her...

The effect of protease inhibitors derived from potato formulated in a minidrink on appetite, food intake and plasma cholecystokinin levels in humans

Protease inhibitor 2 derived from potato (PI2) is claimed to reduce appetite and food intake, stimulate the satiety hormone cholecystokinin (CCK) and lower postprandial glucose peaks when taken before a meal. However, current literature is inconclusive with regard to its efficacy and mechanism. Furthermore, the potential effect of PI2 on appetite motivational ratings without an immediately following meal has not previously been reported. To comprehensively test the effects of 30 mg PI2 in a minidrink on appetite ratings, subsequent food intake, and plasma CCK and glucose responses. Minidrinks with or without 30 mg PI2 were compared in three separate substudies (A, B and C), each using a two-way, placebo-controlled, balanced-order, cross-over design and 23 or 24 subjects (mean over groups: body mass index 25.0 kg m(-2), range 22.5-30.7 kg m(-2); age 41.3, range 18-62 years). The minidrink was given (A) 120 or (B) 30 min before an ad libitum lunch or (C) 30 min before a fixed lunch. Study parameters were self-reported satiety (substudies A and C), ad libitum meal intake (substudies A and B), and (in an n=12 subset) plasma CCK and blood glucose in all substudies. All results were analyzed using analysis of covariance. Protease-inhibitory activity of the PI2-containing minidrinks was assessed under simulated gut conditions. PI2 did not differ from control for any study parameters, in any substudy, despite confirmation of the inhibitory activity of PI2. In this study protease inhibition using PI2 in a minidrink at a dose of 30 mg, as commercially used, had no (functional) efficacy on a range of behavioral and physiological appetite and intake control measures.

Nonhomeostatic Control of Human Appetite and Physical Activity in Regulation of Energy Balance

Ghrelin and leptin, putative controllers of human appetite, have no effect on human meal-to-meal appetite but respond to variations in energy availability. Nonhomeostatic characteristics of appetite and spontaneous activity stem from inhibition by leptin and ghrelin of brain reward circuit that is responsive to energy deficit, but refractory in obesity, and from the operation of a meal-timing circadian clock.

Effects of fat on appetite and energy intake in humans

Effects of fat on appetite and energy intake in humans

Sizing Up Pharmacotherapy for Obesity

Obesity has increased over the last 20 years, from a condition affecting only a small portion of populations in developed countries, into a global pandemic.1 The impact of obesity can be appreciated in the context of the populations at risk, and it is estimated that >1 billion adults worldwide are overweight (BMI >25 kg/m2), 300 million of whom are clinically obese (BMI >30 kg/m2).2 In the United States, 65% of adults are overweight, and 32.2% of them are obese, a prevalence that has doubled over 20 years.3 In industrialized countries, obesity rates have tripled, coinciding with adoption of a Western lifestyle.4 Further, the growing worldwide rates of childhood obesity have reached epidemic values in developed countries.5 This global obesity pandemic reflects genetic susceptibility, availability of high-energy foods, and decreased physical activity. Accelerating rates of obesity have profound health and economic consequences. Obesity is associated with a myriad of co-morbidities, including type II diabetes, coronary artery disease, obstructive sleep apnea, stroke, cancer, hypertension, osteoarthritis, and liver and biliary disease which collectively increase mortality.6 Indeed, the health care impact of chronic obesity exceeds that of smoking or alcohol abuse.7 National health care costs of obesity are $70–100 billion, and if this trend continues, in 15 years 20% of health care costs in the United States will be attributed to the chronic diseases associated with obesity.8 Collectively, these considerations underscore the health and economic imperative to develop novel therapeutic approaches to combat obesity and its co-morbidities. In that context, overweight and obese individuals who receive assistance from their health care providers to lose weight are three times more likely to attempt weight loss.9 The most common approach to medical weight management is counseling and lifestyle modification. However, while patients enrolled in these programs initially lose weight, they usually regain 30–35% of their lost weight within one year following treatment, and >50% of patients return to their baseline weight by five years.10, 11 At present, only two drugs, orlistat and sibutramine, are approved for the long-term treatment of obesity. However, due to their inherent cardiovascular and gastrointestinal adverse effects, respectively, these drugs are often only utilized as rescue therapy for patients who fail diet and exercise. The scope of the obesity problem and the absence of available long-term solutions highlights the unmet clinical need for safe and effective pharmacotherapeutics to induce and maintain weight loss.