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However, whether it is harmful or beneficial for subjects with mild cardiovascular diseases or even those without clinical manifestations is still controversial, likely because of the following reasons: (i) similar strains of mice in different studies from different suppliers differ in baseline bacterial gut microbiome, diet (e.g., different choline levels), age of the mice, animal housing conditions, and duration of the experiment

The activity of MC4R is strictly regulated by its endogenous ligands: -melanocyte-stimulating hormone (-MSH) binds to MC4R and transmits anorexigenic and energy-expenditure signals, whereas agouti-related protein (AgRP) exerts an antagonistic effect by binding to the receptor, competitively inhibiting -MSH action and promoting appetite

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