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Ablation of TRPM5 in Mice Results in Reduced Body Weight Gain and Improved Glucose Tolerance and Protects from Excessive Consumption of Sweet Palatable Food when Fed High Caloric Diets.

Larsson MH, Håkansson P, Jansen FP, Magnell K, Brodin P - PLoS ONE (2015)

Bottom Line: In addition it is also found in other types of chemosensory cells in various parts of the body as well as in pancreatic β-cells.A main finding was the clearly improved glucose tolerance in Trpm5-/- mice compared to wild type mice on cafeteria diet, which was independent of body weight.In addition, it was shown that Trpm5-/- mice consumed the same amount of calories when fed a HFD only or a HFD in combination with a palatable chocolate ball, which is in contrast to wild type mice that increased their caloric intake when fed the combination, mainly due to excessive consumption of the chocolate ball.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioscience, Cardiovascular & Metabolic Disease Innovative Medicines, AstraZeneca R&D, Mölndal, Sweden; Department of Discovery Safety, Drug Safety and Metabolism, AstraZeneca R&D, Mölndal, Sweden.

ABSTRACT
The calcium activated cation channel transient receptor potential channel type M5 (TRPM5) is part of the downstream machinery of the taste receptors and have been shown to play a central role in taste signalling. In addition it is also found in other types of chemosensory cells in various parts of the body as well as in pancreatic β-cells. The aim of this study was to investigate the effects of TRPM5 gene ablation on body weight, insulin sensitivity and other metabolic parameters in long-term high caloric diet induced obesity. Trpm5-/- mice gained significantly less body weight and fat mass on both palatable carbohydrate and fat rich cafeteria diet and 60% high fat diet (HFD) and developed less insulin resistance compared to wild type mice. A main finding was the clearly improved glucose tolerance in Trpm5-/- mice compared to wild type mice on cafeteria diet, which was independent of body weight. In addition, it was shown that Trpm5-/- mice consumed the same amount of calories when fed a HFD only or a HFD in combination with a palatable chocolate ball, which is in contrast to wild type mice that increased their caloric intake when fed the combination, mainly due to excessive consumption of the chocolate ball. Thus the palatable sugar containing diet induced overeating was prevented in Trpm5-/- mice. This indicates that sweet taste induced overeating may be a cause for the increased energy intake and glucose intolerance development seen for wild type mice on a sugar and high fat rich cafeteria diet compared to when on a high fat diet. This study point to an important role for the taste signalling system and TRPM5 in diet induced glucose intolerance.

No MeSH data available.


Related in: MedlinePlus

Lickometer taste preference test in male Trpm5-/- and wild type mice.Preferences of 1M sucrose or 10 mM sucralose over water were followed during 4 consecutive days. Average daily number of licks of water and 1M sucrose (A) or 1 mM sucralose (B) for Trpm5-/- and wild type mice were calculated. A preference score (percent licks on the test solution of the total number of licks) were calculated for 1M sucrose (C) and 10 mM sucralose (D). The dashed line (50% preference) indicates when the mouse consume equal amount of water and liquid tastant. Data are presented as mean ± SEM, n = 4, *** p<0.001, water vs sweetener within the same genotype (Students t-test).
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pone.0138373.g008: Lickometer taste preference test in male Trpm5-/- and wild type mice.Preferences of 1M sucrose or 10 mM sucralose over water were followed during 4 consecutive days. Average daily number of licks of water and 1M sucrose (A) or 1 mM sucralose (B) for Trpm5-/- and wild type mice were calculated. A preference score (percent licks on the test solution of the total number of licks) were calculated for 1M sucrose (C) and 10 mM sucralose (D). The dashed line (50% preference) indicates when the mouse consume equal amount of water and liquid tastant. Data are presented as mean ± SEM, n = 4, *** p<0.001, water vs sweetener within the same genotype (Students t-test).

Mentions: To further investigate the ability of the mice to sense and show preference for the nutrient content, a lickometer taste preference test was performed. As reported above, male Trpm5-/- mice did not show an acute preference for either sucrose or the artificial sweetener sucralose as observed with wild type mice. However, after 3 days in the nutrient preference test, Trpm5-/- mice developed a preference for sucrose but not sucralose (Fig 8).


Ablation of TRPM5 in Mice Results in Reduced Body Weight Gain and Improved Glucose Tolerance and Protects from Excessive Consumption of Sweet Palatable Food when Fed High Caloric Diets.

Larsson MH, Håkansson P, Jansen FP, Magnell K, Brodin P - PLoS ONE (2015)

Lickometer taste preference test in male Trpm5-/- and wild type mice.Preferences of 1M sucrose or 10 mM sucralose over water were followed during 4 consecutive days. Average daily number of licks of water and 1M sucrose (A) or 1 mM sucralose (B) for Trpm5-/- and wild type mice were calculated. A preference score (percent licks on the test solution of the total number of licks) were calculated for 1M sucrose (C) and 10 mM sucralose (D). The dashed line (50% preference) indicates when the mouse consume equal amount of water and liquid tastant. Data are presented as mean ± SEM, n = 4, *** p<0.001, water vs sweetener within the same genotype (Students t-test).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4580452&req=5

pone.0138373.g008: Lickometer taste preference test in male Trpm5-/- and wild type mice.Preferences of 1M sucrose or 10 mM sucralose over water were followed during 4 consecutive days. Average daily number of licks of water and 1M sucrose (A) or 1 mM sucralose (B) for Trpm5-/- and wild type mice were calculated. A preference score (percent licks on the test solution of the total number of licks) were calculated for 1M sucrose (C) and 10 mM sucralose (D). The dashed line (50% preference) indicates when the mouse consume equal amount of water and liquid tastant. Data are presented as mean ± SEM, n = 4, *** p<0.001, water vs sweetener within the same genotype (Students t-test).
Mentions: To further investigate the ability of the mice to sense and show preference for the nutrient content, a lickometer taste preference test was performed. As reported above, male Trpm5-/- mice did not show an acute preference for either sucrose or the artificial sweetener sucralose as observed with wild type mice. However, after 3 days in the nutrient preference test, Trpm5-/- mice developed a preference for sucrose but not sucralose (Fig 8).

Bottom Line: In addition it is also found in other types of chemosensory cells in various parts of the body as well as in pancreatic β-cells.A main finding was the clearly improved glucose tolerance in Trpm5-/- mice compared to wild type mice on cafeteria diet, which was independent of body weight.In addition, it was shown that Trpm5-/- mice consumed the same amount of calories when fed a HFD only or a HFD in combination with a palatable chocolate ball, which is in contrast to wild type mice that increased their caloric intake when fed the combination, mainly due to excessive consumption of the chocolate ball.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioscience, Cardiovascular & Metabolic Disease Innovative Medicines, AstraZeneca R&D, Mölndal, Sweden; Department of Discovery Safety, Drug Safety and Metabolism, AstraZeneca R&D, Mölndal, Sweden.

ABSTRACT
The calcium activated cation channel transient receptor potential channel type M5 (TRPM5) is part of the downstream machinery of the taste receptors and have been shown to play a central role in taste signalling. In addition it is also found in other types of chemosensory cells in various parts of the body as well as in pancreatic β-cells. The aim of this study was to investigate the effects of TRPM5 gene ablation on body weight, insulin sensitivity and other metabolic parameters in long-term high caloric diet induced obesity. Trpm5-/- mice gained significantly less body weight and fat mass on both palatable carbohydrate and fat rich cafeteria diet and 60% high fat diet (HFD) and developed less insulin resistance compared to wild type mice. A main finding was the clearly improved glucose tolerance in Trpm5-/- mice compared to wild type mice on cafeteria diet, which was independent of body weight. In addition, it was shown that Trpm5-/- mice consumed the same amount of calories when fed a HFD only or a HFD in combination with a palatable chocolate ball, which is in contrast to wild type mice that increased their caloric intake when fed the combination, mainly due to excessive consumption of the chocolate ball. Thus the palatable sugar containing diet induced overeating was prevented in Trpm5-/- mice. This indicates that sweet taste induced overeating may be a cause for the increased energy intake and glucose intolerance development seen for wild type mice on a sugar and high fat rich cafeteria diet compared to when on a high fat diet. This study point to an important role for the taste signalling system and TRPM5 in diet induced glucose intolerance.

No MeSH data available.


Related in: MedlinePlus