Abstract: The invention concerns a method of reducing body fat content of a subject in need thereof, the method comprising administering to the subject an agent capable of down-regulating activity and/or expression of at least one component participating in protein digestion and/or absorption. Such agents may be (i) an oligonucleotide directed to an endogenous nucleic acid sequence expressing said at least one component participating in said protein digestion and/or absorption or (ii) a protease inhibitor directed to said at least one component participating in protein digestion and/or absorption. The invention is particularly directed to a method of reducing body fat content of a subject in need thereof, the method comprising administering to the subject serine protease inhibitor inhibiting both enteropeptidase and trypsin activity.