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The significance of this paper is not only to compare the three routes of administration but also to evaluate them and determine which route is the best to administrate the drug

However, studies using beta-3-adrenergic receptor knockout mice revealed a more complex picture: Long-term AOD-9604 treatment failed to produce weight loss in beta-3-AR knockout mice Acute administration still increased energy expenditure and fat oxidation in knockout mice This suggests beta-3-AR expression enhancement contributes to, but does not directly mediate, lipolytic effects The peptide appears to work through an unidentified receptor mechanism that subsequently influences beta-3-adrenergic signaling pathways

The high fat content in KD lowers the oesophageal sphincter tone, slows gastric emptying, and decreases intestinal transit time 4,5

GIP has been shown to decrease food intake while blunting the metabolic adaptive responses that usually occur with calorie restriction resulting in weight reductions, and when combined with GLP-1 receptor agonism, may result in greater effects on markers of metabolic dysregulation such as body weight, glucose and lipids