Obesity and overweight pose serious risk for many diseases and clinical conditions. However currently available weight loss strategies and pharmacotherapies of obesity are not satisfactory. This study shows that treatments with pH modifiers such as acids are not only well tolerated by obese mice but also very effective in reducing bodyweight and fat mass by depleting and suppressing the proliferation of proliferating epithelial cells of the intestinal villi. Therefore other cell proliferation inhibitors that suppress intestinal epithelial renewal can also be used for pharmacotherapy of obesity and overweight.