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Lipid-induced pramlintide release from genetically modified cells transiently reduces weight gain in rats


Roch, Marie. Lipid-induced pramlintide release from genetically modified cells transiently reduces weight gain in rats. 2016, University of Zurich, Vetsuisse Faculty.

Abstract

Amylin is an important control of energy homeostasis and it enhances leptin signaling in the mediobasal hypothalamus. The amylin analogue pramlintide has been used clinically as an adjunct to insulin therapy in type 1 and 2 diabetes to better control postprandial glucose levels and has been previously shown to reduce body weight and energy intake. Here, a new approach was used to deliver pramlintide. HT-1080 cells were co-transfected with the lipid-sensing receptor (LSR) plasmid (pKR135) and the LSR-controlled pramlintide plasmid (pKR146). These cells were microencapsulated in alginate beads and injected intraperitoneally in male Sprague-Dawley rats maintained on high fat diet (60% fat). 20 x 106 cells (pKR135/pKR146-engineered cells) were injected per rat; the control group was implanted with pKR135-engineered cells. Rats injected with the pramlintide secreting cells had significantly lower food intake on day 1, and lower cumulative body weight gain from day 2 to day 5 as compared to controls. Pramlintide reduced food intake by 26% during a meal test on day 3; this effect was associated with an increase in plasma pramlintide levels. Leptin’s effect on 4h-food intake was amplified by 33% in rats injected with pramlintide beads tested 5 and 7 days after implantation. The current study demonstrated the successful but transient effect of an autonomous genetic system providing fatty acid-induced production and secretion of pramlintide in rats put on high fat diet.

Abstract

Amylin is an important control of energy homeostasis and it enhances leptin signaling in the mediobasal hypothalamus. The amylin analogue pramlintide has been used clinically as an adjunct to insulin therapy in type 1 and 2 diabetes to better control postprandial glucose levels and has been previously shown to reduce body weight and energy intake. Here, a new approach was used to deliver pramlintide. HT-1080 cells were co-transfected with the lipid-sensing receptor (LSR) plasmid (pKR135) and the LSR-controlled pramlintide plasmid (pKR146). These cells were microencapsulated in alginate beads and injected intraperitoneally in male Sprague-Dawley rats maintained on high fat diet (60% fat). 20 x 106 cells (pKR135/pKR146-engineered cells) were injected per rat; the control group was implanted with pKR135-engineered cells. Rats injected with the pramlintide secreting cells had significantly lower food intake on day 1, and lower cumulative body weight gain from day 2 to day 5 as compared to controls. Pramlintide reduced food intake by 26% during a meal test on day 3; this effect was associated with an increase in plasma pramlintide levels. Leptin’s effect on 4h-food intake was amplified by 33% in rats injected with pramlintide beads tested 5 and 7 days after implantation. The current study demonstrated the successful but transient effect of an autonomous genetic system providing fatty acid-induced production and secretion of pramlintide in rats put on high fat diet.

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Additional indexing

Item Type:Dissertation
Referees:Lutz Thomas A, Langhans Wolfgang
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Physiology
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2016
Deposited On:18 Oct 2017 16:18
Last Modified:02 Feb 2018 12:32
Number of Pages:28
OA Status:Green
Related URLs:https://www.recherche-portal.ch/ZAD:default_scope:ebi01_prod010831854 (Library Catalogue)

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