Demi
Wed, Nov-27-13, 03:20
From The Times
London, UK
27 November, 2013
Implant that tells you when you’re full may replace gastric bands
An implant that prevents weight gain by sending out signals to block appetite has been developed by scientists. The device, which was shown to be effective at reducing weight in obese mice, could provide an alternative to gastric band surgery. The implant contains genetically engineered cells, designed to respond to fat in the bloodstream by producing a powerful hormone signal that tells the brain: “You’re full, stop eating.”
Martin Fussenegger, who led the research at the Swiss Federal Institute of Technology in Zurich, said that the human natural feedback circuit is weaker because it takes into account factors such as whether we find food tasty. “Often we override our sensing circuitry because we like the food and want to eat more,” he said. “The implant short-circuits this, giving an appetite- reducing signal.”
Professor Fussenegger hopes to develop a similar implant for use in humans, but not everybody is convinced. Sir Stephen O’Rahilly, a professor of Clinical Biochemistry and Medicine at the University of Cambridge, said: “This is elegant technology, but its likely applicability to humans in the near future is low.”
The implant, described yesterday in the journal Nature Communications, comprised gel capsules each containing hundreds of human cells. These were genetically engineered to increase the activity of a gene, PPAR-alpha, which responds to circulating fats in the body.
The cells were modified so that when the PPAR-alpha gene was activated, it triggered the production of pramlintide, a hormone which suppresses appetite.
A few hundred capsules were implanted in overweight mice, and they stopped eating and lost weight. As blood-fat levels returned to normal, the implant stopped producing the “satiety” signal.
“The mice lost weight, although we kept giving them as much high-calorie food as they could eat,” Professor Fussenegger said. Mice that were a healthy weight and on a normal diet did not lose weight or reduce their intake of food when they had the device implanted.
The researchers hope that, in humans, the capsules could be put in a sachet that would be inserted under the skin. Professor Fussenegger said that it might be necessary to use genetically engineered copies of a patient’s cells to prevent rejection by the immune system — and that could be costly. http://www.thetimes.co.uk/tto/science/article3933123.ece
From Nature Communications
26 November, 2013
A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice
ABSTRACT
Diet-induced obesity is a lifestyle-associated medical condition that increases the risk of developing cardiovascular disease, type 2 diabetes and certain types of cancer. Here we report the design of a closed-loop genetic circuit that constantly monitors blood fatty acid levels in the setting of diet-associated hyperlipidemia and coordinates reversible and adjustable expression of the clinically licensed appetite-suppressing peptide hormone pramlintide. Grafting of the peroxisome proliferator-activated receptor-α onto the phloretin-responsive repressor TtgR produces a synthetic intracellular lipid-sensing receptor (LSR) that reversibly induces chimeric TtgR-specific promoters in a fatty acid-adjustable manner. Mice with diet-induced obesity in which microencapsulated cells engineered for LSR-driven expression of pramlintide are implanted show significant reduction in food consumption, blood lipid levels and body weight when put on a high-fat diet. Therapeutic designer circuits that monitor levels of pathologic metabolites and link these with the tailored expression of protein pharmaceuticals may provide new opportunities for the treatment of metabolic disorders.Read the full article here: http://www.nature.com/ncomms/2013/131126/ncomms3825/full/ncomms3825.html
London, UK
27 November, 2013
Implant that tells you when you’re full may replace gastric bands
An implant that prevents weight gain by sending out signals to block appetite has been developed by scientists. The device, which was shown to be effective at reducing weight in obese mice, could provide an alternative to gastric band surgery. The implant contains genetically engineered cells, designed to respond to fat in the bloodstream by producing a powerful hormone signal that tells the brain: “You’re full, stop eating.”
Martin Fussenegger, who led the research at the Swiss Federal Institute of Technology in Zurich, said that the human natural feedback circuit is weaker because it takes into account factors such as whether we find food tasty. “Often we override our sensing circuitry because we like the food and want to eat more,” he said. “The implant short-circuits this, giving an appetite- reducing signal.”
Professor Fussenegger hopes to develop a similar implant for use in humans, but not everybody is convinced. Sir Stephen O’Rahilly, a professor of Clinical Biochemistry and Medicine at the University of Cambridge, said: “This is elegant technology, but its likely applicability to humans in the near future is low.”
The implant, described yesterday in the journal Nature Communications, comprised gel capsules each containing hundreds of human cells. These were genetically engineered to increase the activity of a gene, PPAR-alpha, which responds to circulating fats in the body.
The cells were modified so that when the PPAR-alpha gene was activated, it triggered the production of pramlintide, a hormone which suppresses appetite.
A few hundred capsules were implanted in overweight mice, and they stopped eating and lost weight. As blood-fat levels returned to normal, the implant stopped producing the “satiety” signal.
“The mice lost weight, although we kept giving them as much high-calorie food as they could eat,” Professor Fussenegger said. Mice that were a healthy weight and on a normal diet did not lose weight or reduce their intake of food when they had the device implanted.
The researchers hope that, in humans, the capsules could be put in a sachet that would be inserted under the skin. Professor Fussenegger said that it might be necessary to use genetically engineered copies of a patient’s cells to prevent rejection by the immune system — and that could be costly. http://www.thetimes.co.uk/tto/science/article3933123.ece
From Nature Communications
26 November, 2013
A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice
ABSTRACT
Diet-induced obesity is a lifestyle-associated medical condition that increases the risk of developing cardiovascular disease, type 2 diabetes and certain types of cancer. Here we report the design of a closed-loop genetic circuit that constantly monitors blood fatty acid levels in the setting of diet-associated hyperlipidemia and coordinates reversible and adjustable expression of the clinically licensed appetite-suppressing peptide hormone pramlintide. Grafting of the peroxisome proliferator-activated receptor-α onto the phloretin-responsive repressor TtgR produces a synthetic intracellular lipid-sensing receptor (LSR) that reversibly induces chimeric TtgR-specific promoters in a fatty acid-adjustable manner. Mice with diet-induced obesity in which microencapsulated cells engineered for LSR-driven expression of pramlintide are implanted show significant reduction in food consumption, blood lipid levels and body weight when put on a high-fat diet. Therapeutic designer circuits that monitor levels of pathologic metabolites and link these with the tailored expression of protein pharmaceuticals may provide new opportunities for the treatment of metabolic disorders.Read the full article here: http://www.nature.com/ncomms/2013/131126/ncomms3825/full/ncomms3825.html