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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

Schematic presentation of the experimental protocols used in the long term diet studies.From 12 weeks of age female Trpm5-/- and wild type mice were fed normal mouse chow together with a cafeteria diet (high fat-high sugar) (n = 5-7/strain) (A) or a 60% HFD only (n = 13-15/strain) (B). The mice were weighed weekly, oral glucose tolerance tests (OGTTs) were performed at the start of the study and at different time-points during the studies and a DEXA scan was run at the end of the studies. In the female 60% HFD study, food intake was recorded for 4 days at 3 different occasions. C; Male Trpm5-/- and wild type mice were fed 60% HFD (n = 8/strain) from the age of 15 weeks.The mice were weighed weekly and energy expenditure, OGTT and DEXA scan were performed before and after the diet treatment. FI = Food Intake, EE = Energy Expenditure.
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pone.0138373.g001: Schematic presentation of the experimental protocols used in the long term diet studies.From 12 weeks of age female Trpm5-/- and wild type mice were fed normal mouse chow together with a cafeteria diet (high fat-high sugar) (n = 5-7/strain) (A) or a 60% HFD only (n = 13-15/strain) (B). The mice were weighed weekly, oral glucose tolerance tests (OGTTs) were performed at the start of the study and at different time-points during the studies and a DEXA scan was run at the end of the studies. In the female 60% HFD study, food intake was recorded for 4 days at 3 different occasions. C; Male Trpm5-/- and wild type mice were fed 60% HFD (n = 8/strain) from the age of 15 weeks.The mice were weighed weekly and energy expenditure, OGTT and DEXA scan were performed before and after the diet treatment. FI = Food Intake, EE = Energy Expenditure.

Mentions: Two separate long-term high caloric diet studies were performed using either cafeteria diet or HFD in female mice (4–5 mice/cage), starting at an age of 12 weeks. In the first high caloric diet study female Trpm5-/- and wild type mice were given, in addition to regular mouse chow (R3, Lactamine AB, Stockholm, Sweden, 3.0 Kcal/g), a high energy fat and sugar containing cafeteria diet consisting of nougat (Odense Marcipanfabrik, Odense, Denmark, 5.6 Kcal/g), chocolate ball (Delicatoboll, Delicato Bakverk AB, Huddinge, Sweden, 5.0 Kcal/g), chocolate (Marabou milk chocolate, Marabou Sweden, 5.4 Kcal/g) and cheese (Västervik Gräddost, Arla Foods, Sweden, 4.2 Kcal/g) (Table 1) for 40 weeks. In the second high caloric diet study, female Trpm5-/- and wild type mice were given a HFD containing (energy percentage) 60% fat, 20% carbohydrates, and 20% protein (D12492; Research Diets, New Brunswick, NJ, USA, 5.2 Kcal/g, Table 1) for 40 weeks. In both studies, the mice were weighed weekly, an oral glucose tolerance test (OGTT) was performed at the start of the studies and at different time-points during the studies and body composition analysis was performed at the end of the studies (Fig 1). At the day of termination (9–11 a.m.), plasma was isolated from isoflurane anesthetized mice and organs were collected, weighed and snap frozen in liquid N2 and stored at -80°C for further analysis of metabolic parameters.


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)

Schematic presentation of the experimental protocols used in the long term diet studies.From 12 weeks of age female Trpm5-/- and wild type mice were fed normal mouse chow together with a cafeteria diet (high fat-high sugar) (n = 5-7/strain) (A) or a 60% HFD only (n = 13-15/strain) (B). The mice were weighed weekly, oral glucose tolerance tests (OGTTs) were performed at the start of the study and at different time-points during the studies and a DEXA scan was run at the end of the studies. In the female 60% HFD study, food intake was recorded for 4 days at 3 different occasions. C; Male Trpm5-/- and wild type mice were fed 60% HFD (n = 8/strain) from the age of 15 weeks.The mice were weighed weekly and energy expenditure, OGTT and DEXA scan were performed before and after the diet treatment. FI = Food Intake, EE = Energy Expenditure.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0138373.g001: Schematic presentation of the experimental protocols used in the long term diet studies.From 12 weeks of age female Trpm5-/- and wild type mice were fed normal mouse chow together with a cafeteria diet (high fat-high sugar) (n = 5-7/strain) (A) or a 60% HFD only (n = 13-15/strain) (B). The mice were weighed weekly, oral glucose tolerance tests (OGTTs) were performed at the start of the study and at different time-points during the studies and a DEXA scan was run at the end of the studies. In the female 60% HFD study, food intake was recorded for 4 days at 3 different occasions. C; Male Trpm5-/- and wild type mice were fed 60% HFD (n = 8/strain) from the age of 15 weeks.The mice were weighed weekly and energy expenditure, OGTT and DEXA scan were performed before and after the diet treatment. FI = Food Intake, EE = Energy Expenditure.
Mentions: Two separate long-term high caloric diet studies were performed using either cafeteria diet or HFD in female mice (4–5 mice/cage), starting at an age of 12 weeks. In the first high caloric diet study female Trpm5-/- and wild type mice were given, in addition to regular mouse chow (R3, Lactamine AB, Stockholm, Sweden, 3.0 Kcal/g), a high energy fat and sugar containing cafeteria diet consisting of nougat (Odense Marcipanfabrik, Odense, Denmark, 5.6 Kcal/g), chocolate ball (Delicatoboll, Delicato Bakverk AB, Huddinge, Sweden, 5.0 Kcal/g), chocolate (Marabou milk chocolate, Marabou Sweden, 5.4 Kcal/g) and cheese (Västervik Gräddost, Arla Foods, Sweden, 4.2 Kcal/g) (Table 1) for 40 weeks. In the second high caloric diet study, female Trpm5-/- and wild type mice were given a HFD containing (energy percentage) 60% fat, 20% carbohydrates, and 20% protein (D12492; Research Diets, New Brunswick, NJ, USA, 5.2 Kcal/g, Table 1) for 40 weeks. In both studies, the mice were weighed weekly, an oral glucose tolerance test (OGTT) was performed at the start of the studies and at different time-points during the studies and body composition analysis was performed at the end of the studies (Fig 1). At the day of termination (9–11 a.m.), plasma was isolated from isoflurane anesthetized mice and organs were collected, weighed and snap frozen in liquid N2 and stored at -80°C for further analysis of metabolic parameters.

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