Help
Subscribe


GastroHep.com - the global online resource for all aspects of gastroenterology, hepatology and endoscopy

 19 November 2017

Advanced search
GastroHep.com - the global online resource for all aspects of gastroenterology, hepatology and endoscopy Profile of Roy Pounder

Home

News  
Journals
Review Articles
Slide Atlas
Video Clips
Online Books
Advanced Digestive Endoscopy
Classical Cases
Conference Diary
PubMed
International GH Links
USA GH Links
National GH Links
National GI Societies
Other Useful Links




Emails on Gastroenterology and Hepatology
the National AIDS Treatment Advocacy Project
Visit the gastroenterology section of the EUMS

News

Gut-derived hormone could help in search for obesity treatment

Scientists claim to have found a 'fullness' hormone that could lead to new drugs to help treat obesity.

News image

fiogf49gjkf04

They claim, in this week's Nature, that it travels to the brain's hypothalamus, where it shuts down nerves that trigger eating.

Volunteers injected with the hormone, called PYY3-36, helped themselves to one-third less food from a free buffet, Dr Stephen Bloom of Imperial College, London, and his colleagues discovered, and ate less for up to 12 hours.

Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus of the brain.

Within the arcuate nucleus, which is accessible to peripheral hormones, these 2 distinct subsets of neurons control food intake by acting in opposing manners to one other.

'Accelerator' neurons produce NPY, which acts in the brain to stimulate feeding, while adjacent 'braking' neurons produce melanocortin peptides. These act on the same areas of the brain as NPY, but inhibit eating.

During weight loss for example, NPY-expressing neurons are activated and melanocortin-producing neurons are inhibited - responses that stimulate eating and promote the recovery of depleted fuel stores when sufficient food becomes available.

Within the NPY system is a highly expressed presynaptic receptor named Y2R (NPY Y2 receptor).

A known agonist of Y2R is peptide YY3-36 (PYY3-36), a gut-derived hormone that is released post-prandially in proportion to the calorific intake.

This hormone, which is made by endocrine cells lining the distal small bowel and colon, rises in the blood after eating and remains high between meals.

Dr Bloom and his colleagues therefore investigated the effects of peripheral administration of PYY3-36 on feeding.

Initially using rodent studies, intra-peritoneal injection of PYY3-36 was shown to reduce both food intake and weight gain in rats.

Studies in Y2r-null mice also showed that the hormone could inhibit food intake, but no longer had an anorexic action, suggesting that PYY3-36 may require Y2R for mediation of this effect.

Using a combination of electrophysiological and hypothalamic explant studies, the research group were able to show that PYY3-36 can directly influence hypothalamic circuits, resulting in co-ordinate changes in the action of adjacent pro-opiomelanocortin and NPY neurons.

In addition, PYY3-36 administered directly into this region of the brain was also shown to reduce food intake.

12 healthy fasted, non-obese volunteers (six men and six women: mean age, 26.7 ±0.7 years; BMI, 24.6 ±0.94 kg m-2) were then recruited to examine the effects of PYY3-36 in humans.

PYY3-36 infusion reduced calorie intake by a third
Nature

The volunteers were infused with PYY3-36 (0.8 pmol per kg (body weight) per min) or saline for 90 minutes, in a double-blind, placebo-controlled crossover study.

PYY3-36 plasma concentrations were found to increase from a mean basal concentration of 8.3 ±1.0 pM to a maximum of 43.5 ±3 pM during the
PYY3-36 infusion and mimicked post-prandial concentrations.

After infusion, PYY3-36 concentrations returned to basal levels within 30 minutes, but resulted in a significant decrease in hunger scores, as assessed by a visual analogue scale.

2 hours after terminating the infusion, subjects were offered an excess free-choice buffet meal, such that all appetites could be satisfied. Food and water were weighed pre- and post-prandially, and caloric intake was calculated.

The researchers found that in the PYY3-36-infused subjects, calorie intake was reduced by more than a third compared with saline controls (36 ±7.4%).

However, there was no effect on fluid intake and no difference in sensations of fullness or nausea reported by the volunteers.

PYY3-36 administration also had no effect on gastric emptying, as estimated by the paracetamol absorption method, or on plasma glucose, plasma leptin or insulin.

Analysis of food diaries kept by the volunteers showed a significant inhibition of food intake in the 12-hour period after the PYY3-36 infusion (saline group, 2,205 ±243 kcal versus PYY3-36 group, 1,474 ±207 kcal).

Over the 12-hour to 24-hour period however, food intake between the two groups was virtually identical.

Overall there was a 33% decrease in cumulative total calorie consumption in the 24-hour period after the PYY3-36 infusion.

Commenting on the results of the studies, Dr Bloom said they showed that post-prandial concentrations of PYY3-36 inhibit food intake in both rodents and man for up to 12 hours, suggesting a role for PYY3-36 in 'longer term' regulation of food intake.

"It's what stops you having the third helping," he joked.

This contrasts with previously characterized gut-derived 'short-term' satiety signals such as cholecystokinin1, the effects of which are relatively short-lived.

Continuing, Dr Bloom said, "The failure of PYY3-36 to inhibit food intake in the Y2r-null mice provides further evidence that PYY3-36 reduces food intake through a Y2R-dependent mechanism."

"Our results suggest that a gut-hypothalamic pathway that involves postprandial PYY3-36 acting at the arcuate Y2R has a role in regulating feeding."

Researchers hope that the PYY3-36 system may provide a therapeutic target for the treatment of obesity.

Drugs mimicking the peptide hormone and taken before mealtimes might work to curb appetite and help fight weight gain.

"If we are to combat the global obesity epidemic, such breakthroughs are urgently needed," said Michael Schwartz of the University of Washington in Seattle, USA, in an accompanying News and Views article.

Nature 2002; 418(6898): 650-654
09 August 2002

Go to top of page Email this page Email this page to a colleague

 17 November 2017 
Food elimination diets for treatment of adults with eosinophilic esophagitis
 17 November 2017 
PPI use and cognitive function in women
 17 November 2017 
Predicting microscopic colitis
 16 November 2017 
NAFLD-hepatocellular carcinoma and survival after orthotopic liver transplant
 16 November 2017 
Prepregnancy obesity and severe maternal morbidity
 16 November 2017 
Celiac disease screening in adult first-degree relatives
 15 November 2017 
Breastfeeding and the risk of IBD
 15 November 2017 
Medication nonadherence and health care costs
 15 November 2017 
Predicting recurrence after curative rectal cancer surgery
 14 November 2017 
HBV/HCV coinfection and cirrhosis
 14 November 2017 
Sexual dysfunction after rectal cancer surgery
 14 November 2017 
Eosinophilic gastroenteritis and colitis
 13 November 2017 
GI bleeding in patients taking non–vitamin K antagonist oral anticoagulants
 13 November 2017 
Genetic polymorphisms, fatty acids and ulcerative colitis
 13 November 2017 
Flares after immunomodulator withdrawal in Crohn's
 10 November 2017 
Thiopurines vs TNF and lymphoma risk in IBD
 10 November 2017 
Drug monitoring of anti-tumour necrosis factor therapy in IBD
 10 November 2017 
Treatment decisions for older patients with colorectal cancer
 09 November 2017 
Quality standards in upper gastrointestinal endoscopy
 09 November 2017 
Irradiated rectal cancer and chemoradiotherapy
 09 November 2017 
Environmental factors and IBD
 08 November 2017 
Prophylaxis of spontaneous bacterial peritonitis
 08 November 2017 
Socioeconomic characteristics in diverticular disease
 08 November 2017 
Optimal management of postoperative Crohn's disease
 07 November 2017 
Community Screening for Helicobacter pylori
 07 November 2017 
Early readmission in IBD patients
 07 November 2017 
Mesocolic excision for colon cancer
 06 November 2017 
Food elimination diet for children with eosinophilic esophagitis
 06 November 2017 
Biologic agents and obesity in children with IBD
 06 November 2017 
Liver cancer burden despite extensive use of antiviral agents
 03 November 2017 
Statins and mortality in chronic viral hepatitis
 03 November 2017 
Propofol for outpatient colonoscopy
 03 November 2017 
Asthma and IBD development
 02 November 2017 
Diverticulitis and emergency department burden
 02 November 2017 
Rural residence and risk of IBD
 02 November 2017 
Sexual functioning in Hep C
 01 November 2017 
Heartburn relief in adolescents with GERD
 01 November 2017 
Barriers to hepatitis C treatment
 01 November 2017 
Autoimmune pancreatitis in children
 31 October 2017 
Surveillance in ulcerative colitis and Crohn’s disease
 31 October 2017 
Endoscopic indices of disease activity for Crohn’s
 31 October 2017 
Follow-up of positive results on fecal blood tests
 30 October 2017 
Local recurrence after curative rectal cancer surgery
 30 October 2017 
Low-flow ascites pump in refractory cirrhosis
 30 October 2017 
Medical therapy of patients with pediatric-onset IBD
 27 October 2017 
NAFLD in advanced fibrosis in the USA
 27 October 2017 
Early readmission in cirrhosis after bacterial infections
 26 October 2017 
Predicting response to anti-TNF therapy in Crohn's
 26 October 2017 
Conversion to open laparotomy in rectal cancer
 25 October 2017 
Conversion of colonoscopy to sigmoidoscopy
 25 October 2017 
Fecal microbiota transplantation
 25 October 2017 
Rifaximin and survival in hepatic encephalopathy
 24 October 2017 
Eosinophilic esophagitis with swallowed topical corticosteroids
 24 October 2017 
Meta-analysis in nutritiona research
 23 October 2017 
NAFLD-related hepatocellular carcinoma in liver resection
 23 October 2017 
Outcome of hepatic sarcoidosis
 20 October 2017 
Hospital readmissions reduction program
 20 October 2017 
Conversion of planned colonoscopy to sigmoidoscopy
 19 October 2017 
Fecal immunochemical tests in colorectal cancer screening
 19 October 2017 
Current management of chylous ascites

Blackwell Publishing


GastroHep.com is a Blackwell Publishing registered trademark
© 2017 Wiley-Blackwell and GastroHep.com and contributors
Privacy Statement
Disclaimer
About Us