scholarly journals The Effect of a Subcutaneous Infusion of GLP-1, OXM, and PYY on Energy Intake and Expenditure in Obese Volunteers

2017 ◽  
Vol 102 (7) ◽  
pp. 2364-2372 ◽  
Author(s):  
Tricia Tan ◽  
Preeshila Behary ◽  
George Tharakan ◽  
James Minnion ◽  
Werd Al-Najim ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Energy Intake ◽  
Peptide Yy ◽  
Gut Hormones ◽  
Resting Energy Expenditure ◽  
Subcutaneous Infusion ◽  
Glucagon Like Peptide 1 ◽  
Treatment Of Obesity ◽  
First Time

Abstract Background: Roux-en-Y gastric bypass (RYGB) surgery is currently the most effective treatment of obesity, although limited by availability and operative risk. The gut hormones Glucagon-like peptide-1 (GLP-1), Peptide YY (PYY), and Oxyntomodulin (OXM) are elevated postprandially after RYGB, which has been postulated to contribute to its metabolic benefits. Objective: We hypothesized that infusion of the three gut hormones to achieve levels similar to those encountered postprandially in RYGB patients might be effective in suppressing appetite. The aim of this study was to investigate the effect of a continuous infusion of GLP-1, OXM, and PYY (GOP) on energy intake and expenditure in obese volunteers. Methods: Obese volunteers were randomized to receive an infusion of GOP or placebo in a single-blinded, randomized, placebo-controlled crossover study for 10.5 hours a day. This was delivered subcutaneously using a pump device, allowing volunteers to remain ambulatory. Ad libitum food intake studies were performed during the infusion, and energy expenditure was measured using a ventilated hood calorimeter. Results: Postprandial levels of GLP-1, OXM, and PYY seen post RYGB were successfully matched using 4 pmol/kg/min, 4 pmol/kg/min, and 0.4 pmol/kg/min, respectively. This dose led to a mean reduction of 32% in food intake. No significant effects on resting energy expenditure were observed. Conclusion: This is, to our knowledge, the first time that an acute continuous subcutaneous infusion of GOP, replicating the postprandial levels observed after RYGB, is shown to be safe and effective in reducing food intake. This data suggests that triple hormone therapy might be a useful tool against obesity.

scholarly journals How Satiating Are the ‘Satiety’ Peptides: A Problem of Pharmacology versus Physiology in the Development of Novel Foods for Regulation of Food Intake

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1517 ◽  
Author(s):  
Jia Jiet Lim ◽  
Sally D. Poppitt
Keyword(s):  
Weight Loss ◽  
Food Intake ◽  
Energy Intake ◽  
Peptide Yy ◽  
Behavioural Change ◽  
Eating Behaviour ◽  
Predictive Biomarkers ◽  
Negative Energy ◽  
Novel Foods ◽  
Glucagon Like Peptide 1

Developing novel foods to suppress energy intake and promote negative energy balance and weight loss has been a long-term but commonly unsuccessful challenge. Targeting regulation of appetite is of interest to public health researchers and industry in the quest to develop ‘functional’ foods, but poor understanding of the underpinning mechanisms regulating food intake has hampered progress. The gastrointestinal (GI) or ‘satiety’ peptides including cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) secreted following a meal, have long been purported as predictive biomarkers of appetite response, including food intake. Whilst peptide infusion drives a clear change in hunger/fullness and eating behaviour, inducing GI-peptide secretion through diet may not, possibly due to modest effects of single meals on peptide levels. We conducted a review of 70 dietary preload (DIET) and peptide infusion (INFUSION) studies in lean healthy adults that reported outcomes of CCK, GLP-1 and PYY. DIET studies were acute preload interventions. INFUSION studies showed that minimum increase required to suppress ad libitum energy intake for CCK, GLP-1 and PYY was 3.6-, 4.0- and 3.1-fold, respectively, achieved through DIET in only 29%, 0% and 8% of interventions. Whether circulating ‘thresholds’ of peptide concentration likely required for behavioural change can be achieved through diet is questionable. As yet, no individual or group of peptides can be measured in blood to reliably predict feelings of hunger and food intake. Developing foods that successfully target enhanced secretion of GI-origin ‘satiety’ peptides for weight loss remains a significant challenge.

scholarly journals Peptide YY, appetite and food intake

2005 ◽  
Vol 64 (2) ◽  
pp. 213-216 ◽  
Author(s):  
C. W. le Roux ◽  
S. R. Bloom
Keyword(s):  
Food Intake ◽  
Peptide Yy ◽  
Energy Content ◽  
Peak Plasma ◽  
Evolutionary Relationship ◽  
Gut Hormones ◽  
Amino Acid Peptide ◽  
Control Food ◽  
Glucagon Like Peptide 1 ◽  
Control Food Intake

Obesity is taking on pandemic proportions. The laws of thermodynamics, however, remain unchanged, as energy will be stored if less energy is expended than consumed; the storage is usually in the form of adipose tissue. Several neural, humeral and psychological factors control the complex process known as appetite. Recently, a close evolutionary relationship between the gut and brain has become apparent. The gut hormones regulate important gastrointestinal functions such as motility, secretion, absorption, provide feedback to the central nervous system on availability of nutrients and may play a part in regulating food intake. Peptide YY (PYY) is a thirty-six amino acid peptide related to neuropeptide Y (NPY) and is co-secreted with glucagon-like peptide 1. Produced by the intestinal L-cells, the highest tissue concentrations of PYY are found in distal segments of the gastrointestinal tract, although it is present throughout the gut. Following food intake PYY is released into the circulation. PYY concentrations are proportional to meal energy content and peak plasma levels appear postprandially after 1 h. PYY3-36 is a major form of PYY in both the gut mucosal endocrine cells and the circulation. Peripheral administration of PYY3-36 inhibits food intake for several hours in both rodents and man. The binding of PYY3-36 to the Y2 receptor leads to an inhibition of the NPY neurones and a possible reciprocal stimulation of the pro-opiomelanocortin neurones. Thus, PYY3-36 appears to control food intake by providing a powerful feedback on the hypothalamic circuits. The effect on food intake has been demonstrated at physiological concentrations and, therefore, PYY3-36 may be important in the everyday regulation of food intake.

scholarly journals Combination gut hormones: prospects and questions for the future of obesity and diabetes therapy

2020 ◽  
Vol 246 (3) ◽  
pp. R65-R74 ◽  
Author(s):  
Bernard Khoo ◽  
Tricia Mei-Mei Tan
Keyword(s):  
Peptide Yy ◽  
Gut Hormones ◽  
Clinical Results ◽  
Therapeutic Effects ◽  
Physiological Basis ◽  
Obesity And Diabetes ◽  
Gut Hormone ◽  
Glucagon Like Peptide 1 ◽  
Treatment Of Obesity ◽  
Insulinotropic Peptide

Obesity represents an important public health challenge for the twenty-first century: globalised, highly prevalent and increasingly common with time, this condition is likely to reverse some of the hard-won gains in mortality accomplished in previous centuries. In the search for safe and effective therapies for obesity and its companion, type 2 diabetes mellitus (T2D), the gut hormone glucagon-like peptide-1 (GLP-1) has emerged as a forerunner and analogues thereof are now widely used in treatment of obesity and T2D, bringing proven benefits in improving glycaemia and weight loss and, notably, cardiovascular outcomes. However, GLP-1 alone is subject to limitations in terms of efficacy, and as a result, investigators are evaluating other gut hormones such as glucose-dependent insulinotropic peptide (GIP), glucagon and peptide YY (PYY) as possible partner hormones that may complement and enhance GLP-1’s therapeutic effects. Such combination gut hormone therapies are in pharmaceutical development at present and are likely to make it to market within the next few years. This review examines the physiological basis for combination gut hormone therapy and presents the latest clinical results that underpin the excitement around these treatments. We also pose, however, some hard questions for the field which need to be answered before the full benefit of such treatments can be realised.

Effects of varying combinations of intraduodenal lipid and carbohydrate on antropyloroduodenal motility, hormone release, and appetite in healthy males

2009 ◽  
Vol 296 (4) ◽  
pp. R912-R920 ◽  
Author(s):  
Radhika V. Seimon ◽  
Kate L. Feltrin ◽  
James H. Meyer ◽  
Ixchel M. Brennan ◽  
Judith M. Wishart ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Energy Intake ◽  
Peptide Yy ◽  
Gut Hormones ◽  
Double Blind ◽  
Glucose Levels ◽  
Gut Function ◽  
Glucagon Like Peptide 1 ◽  
Desire To Eat ◽  
Healthy Males

Intraduodenal infusions of both lipid and glucose modulate antropyloroduodenal motility and stimulate plasma CCK, with lipid being more potent than glucose. Both stimulate glucagon-like peptide-1, but only lipid stimulates peptide YY (PYY), while only glucose raises blood glucose and stimulates insulin. When administered in combination, lipid and carbohydrate may, thus, have additive effects on energy intake. However, elevated blood glucose levels do not suppress energy intake, and the effect of insulin is controversial. We hypothesized that increasing the ratio of maltodextrin, a complex carbohydrate, relative to lipid would be associated with a reduction in effects on antropyloroduodenal pressures, gut hormones, appetite, and energy intake, when compared with lipid alone. Ten healthy males were studied on three occasions in double-blind, randomized order. Antropyloroduodenal pressures, plasma CCK, PYY and insulin, blood glucose, and appetite were measured during 90-min intraduodenal infusions of 1) 3 kcal/min lipid (L3), 2) 2 kcal/min lipid and 1 kcal/min maltodextrin (L2/CHO1), or 3) 1 kcal/min lipid and 2 kcal/min maltodextrin (L1/CHO2). Energy intake at a buffet lunch consumed immediately after the infusion was quantified. Reducing the lipid (thus, increasing the carbohydrate) content of the infusion was associated with reduced stimulation of basal pyloric pressures ( r = 0.76, P < 0.01), plasma CCK ( r = 0.66, P < 0.01), and PYY ( r = 0.98, P < 0.001), and reduced suppression of antral ( r = −0.64, P < 0.05) and duodenal ( r = −0.69, P < 0.05) pressure waves, desire-to-eat ( r = −0.8, P < 0.001), and energy intake ( r = 0.74, P < 0.01), with no differences in phasic (isolated) pyloric pressures. In conclusion, in healthy males, intraduodenal lipid is a more potent modulator of gut function, associated with greater suppression of energy intake, when compared with isocaloric combinations of lipid and maltodextrin.

scholarly journals The Gut Hormones in Appetite Regulation

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Keisuke Suzuki ◽  
Channa N. Jayasena ◽  
Stephen R. Bloom
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Food Intake ◽  
Peptide Yy ◽  
Critical Role ◽  
Gut Hormones ◽  
Energy Status ◽  
Increased Risk ◽  
Glucagon Like Peptide 1

Obesity has received much attention worldwide in association with an increased risk of cardiovascular diseases, diabetes, and cancer. At present, bariatric surgery is the only effective treatment for obesity in which long-term weight loss is achieved in patients. By contrast, pharmacological interventions for obesity are usually followed by weight regain. Although the exact mechanisms of long-term weight loss following bariatric surgery are yet to be fully elucidated, several gut hormones have been implicated. Gut hormones play a critical role in relaying signals of nutritional and energy status from the gut to the central nervous system, in order to regulate food intake. Cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide-1, and oxyntomodulin act through distinct yet synergistic mechanisms to suppress appetite, whereas ghrelin stimulates food intake. Here, we discuss the role of gut hormones in the regulation of food intake and body weight.

scholarly journals Obesity and Appetite Control

2012 ◽  
Vol 2012 ◽  
pp. 1-19 ◽  
Author(s):  
Keisuke Suzuki ◽  
Channa N. Jayasena ◽  
Stephen R. Bloom
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Peptide Yy ◽  
Gut Hormones ◽  
Appetite Control ◽  
Control Food ◽  
Adiposity Signals ◽  
Term Energy ◽  
Glucagon Like Peptide 1 ◽  
Control Food Intake

Obesity is one of the major challenges to human health worldwide; however, there are currently no effective pharmacological interventions for obesity. Recent studies have improved our understanding of energy homeostasis by identifying sophisticated neurohumoral networks which convey signals between the brain and gut in order to control food intake. The hypothalamus is a key region which possesses reciprocal connections between the higher cortical centres such as reward-related limbic pathways, and the brainstem. Furthermore, the hypothalamus integrates a number of peripheral signals which modulate food intake and energy expenditure. Gut hormones, such as peptide YY, pancreatic polypeptide, glucagon-like peptide-1, oxyntomodulin, and ghrelin, are modulated by acute food ingestion. In contrast, adiposity signals such as leptin and insulin are implicated in both short- and long-term energy homeostasis. In this paper, we focus on the role of gut hormones and their related neuronal networks (the gut-brain axis) in appetite control, and their potentials as novel therapies for obesity.

Increased resting energy expenditure, fat oxidation, and food intake in patients with highly active antiretroviral therapy-associated lipodystrophy

2007 ◽  
Vol 292 (3) ◽  
pp. E687-E692 ◽  
Author(s):  
Jussi Sutinen ◽  
Hannele Yki-Järvinen
Keyword(s):  
Antiretroviral Therapy ◽  
Food Intake ◽  
Energy Expenditure ◽  
Lipid Oxidation ◽  
Energy Intake ◽  
Highly Active Antiretroviral Therapy ◽  
Resting Energy Expenditure ◽  
Fat Free Mass ◽  
Highly Active ◽  
Resting Energy

Highly active antiretroviral therapy (HAART) is associated with metabolic adverse events such as lipodystrophy in human immunodeficiency virus (HIV)-infected patients. The objective of the present study was to evaluate the effects of HAART-associated lipodystrophy on resting energy expenditure and caloric intake. In this cross-sectional study we compared resting energy expenditure (REE) and energy intake in 30 HAART-treated patients with lipodystrophy (HAART+LD+) with 13 HAART-treated patients without lipodystrophy (HAART+LD−). REE was measured using indirect calorimetry, and energy intake was recorded as a 3-day diary of food intake. REE (5,180 ± 160 vs. 4,260 ± 150 J/min, P < 0.01) and also REE expressed per fat-free mass (86 ± 1 vs. 78 ± 2 J·kg fat-free mass−1·min−1, P < 0.01) were significantly higher in the HAART+LD+ than the HAART+LD− group. Rate of lipid oxidation was significantly higher in the HAART+LD+ than the HAART+LD− group. Total energy and fat intakes were significantly increased in the HAART+LD+ compared with the HAART+LD− group. These results imply that HAART-associated lipodystrophy is associated with increased REE and lipid oxidation and with increased caloric and fat intake.

PYY3-36 injection in mice produces an acute anorexigenic effect followed by a delayed orexigenic effect not observed with other anorexigenic gut hormones

2008 ◽  
Vol 294 (4) ◽  
pp. E698-E708 ◽  
Author(s):  
James R. C. Parkinson ◽  
Waljit S. Dhillo ◽  
Caroline J. Small ◽  
Owais B. Chaudhri ◽  
Gavin A. Bewick ◽  
...  
Keyword(s):  
Food Intake ◽  
Peptide Yy ◽  
Gut Hormones ◽  
Reduce Food Intake ◽  
Dark Phase ◽  
Light Phase ◽  
Show Evidence ◽  
Ad Libitum ◽  
Glucagon Like Peptide 1 ◽  
Anorexigenic Effect

Peptide YY (PYY) is secreted postprandially from the endocrine L cells of the gastrointestinal tract. PYY3-36, the major circulating form of the peptide, is thought to reduce food intake in humans and rodents via high-affinity binding to the autoinhibitory neuropeptide Y (NPY) receptor within the arcuate nucleus. We studied the effect of early light-phase injection of PYY3-36 on food intake in mice fasted for 0, 6, 12, 18, 24, and 30 h and show that PYY3-36 produces an acute anorexigenic effect regardless of the duration of fasting. We also show evidence of a delayed orexigenic effect in ad libitum-fed mice injected with PYY3-36 in the early light phase. This delayed orexigenic effect also occurs in mice administered a potent analog of PYY3-36, d-Allo Ile3 PYY3-36, but not following injection of other anorectic agents (glucagon-like-peptide 1, oxyntomodulin, and lithium chloride). Early light-phase injection of PYY3-36 to ad libitum-fed mice resulted in a trend toward increased levels of hypothalamic NPY and agouti-related peptide mRNA and a decrease in proopiomelanocortin mRNA at the beginning of the dark phase. Furthermore, plasma levels of ghrelin were increased significantly, and there was a trend toward decreased plasma PYY3-36 levels at the beginning of the dark phase. These data indicate that PYY3-36 injection results in an acute anorexigenic effect followed by a delayed orexigenic effect.

scholarly journals Energy intake and resting energy expenditure in adult male rats after early postnatal food restriction

2008 ◽  
Vol 99 (5) ◽  
pp. 1149-1156 ◽  
Author(s):  
Floor Remmers ◽  
Michiel F. Schreuder ◽  
Reinoud J. B. J. Gemke ◽  
Henriette A. Delemarre-van de Waal
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Energy Intake ◽  
Food Restriction ◽  
Adult Life ◽  
Resting Energy Expenditure ◽  
Later Life ◽  
Male Rats ◽  
Resting Energy

Both in man and in animal models, changes in food intake and body composition in later life have been reported after alterations in perinatal nutrition. Therefore, we hypothesised that early postnatal undernutrition in the rat induces permanent changes in energy balance. Food restriction (FR) during lactation was achieved by enlarging litter size to twenty pups, whereas control animals were raised in litters containing ten pups. Energy intake and resting energy expenditure were determined in adult males. Early postnatal FR resulted in acute growth restriction followed by incomplete catch-up in body weight, body length and BMI. At the age of 12 months, middle-aged FR males had significantly lower absolute resting energy expenditure (200 v. 216 kJ/24 h, P = 0·009), absolute energy intake (281 v. 310 kJ/24 h, P = 0·001) and energy intake adjusted for BMI (284 v. 305 kJ/24 h, P = 0·016) than controls, whereas resting energy expenditure adjusted for BMI did not differ significantly between the groups (204 v. 211 kJ/24 h, P = 0·156). The amount of energy remaining for other functions was lower in FR males (80 v. 94 kJ/24 h, P = 0·044). Comparable data were obtained at the age of 6 months. These results indicate that in rats energy balance can be programmed by early nutrition. A low early postnatal food intake appears to programme these animals for a low energy intake and to remain slender in adult life.

Sign in / Sign up

Export Citation Format

Share Document