Brown adipose tissue (BAT) is a potential target against obesity and T2D, because activation of BAT induces oxidation of fatty acids and glucose and increases energy expenditure. Theoretically, BAT is activated by beta 3 adrenergic receptors (β3AR). However, β3AR agonists have been unsuccessful in reducing weight and blood glucose in humans. Cold temperatures can also activate BAT and increase the metabolism of fatty acids and glucose. Transient receptor potential cation channel subfamily M member 8 (TRPM8) is a cold-sensing cation channel expressed on BAT and is activated by menthol and icilin, with icilin being more potent.
Diet-induced C57Bl/6J mice (n=17) were divided into four treatment groups: vehicle (100 L s.c); menthol (40mg/kg s.c, 100 L.); low dose of icilin (2mg/kg s.c, 100 L) and high dose of icilin (5mg/kg s.c, 100 L) and treated daily for 1 week. Mice were implanted with biotelemetry devices (G2 E-mitter, STARR Life Sciences Corp, PA, USA). Food intake and body weight were recorded daily. BAT temperature and activity were recorded every minute. Glucose tolerance was assessed by ipGTT before and after 7-days of drug treatment. Body composition was assessed by DEXA (Lunar PIXI densitometer, PIXImus, WI USA) immediately after GTT.
Food Intake
Mice treated with low dose of icilin had significantly reduced food intake on D5-7 (p< 0.05), menthol did not change food intake.
Body Weight and Composition
Low dose icilin reduced body weight on D6-7 (p<0.05). Menthol treatment did not change body weight.
BAT Temperature and Activity
Still being analysed.
Glucose Tolerance
Low dose icilin treatment reduced glucose throughout the GTT (p< 0.05) but did not change baseline or resting blood glucose. Menthol did cause any significant changes to blood glucose.
These results demonstrate that icilin, a TRPM8 agonist, is more potent than menthol at reducing body weight, body fat and glucose tolerance.