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Micelle Sequestrant Polymers as Novel Therapeutics to Treat Obesity
Author(s) -
Sullivan Bradley,
Qian Jian,
Berkland Cory
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1020.10
Subject(s) - bile acid , feces , triglyceride , weight loss , cholesterol , overweight , medicine , micelle , chemistry , population , obesity , absorption (acoustics) , endocrinology , pharmacology , biology , aqueous solution , organic chemistry , paleontology , physics , environmental health , acoustics
Thirty‐five percent of the United States population is classified as overweight or obese. Several options exist to treat obese patients; however, currently available therapies are associated with side effects or poor long term compliance necessitating development of more efficacious and accepted therapeutics for treating obesity. We synthesized and evaluated a library of Micelle Sequestrant Polymers (MSP) as novel orally dosed non‐absorbable molecules that bind intestinal micelles (i.e., dietary triglycerides, bile acids, and cholesterol) and prevent their digestive absorption. Individual MSPs were incorporated into a high fat diet (HFD, 45% kcal from fat) at 0.5% (wt/wt) and fed to mice. Feeding mice a MSP containing HFD increased fecal elimination of triglycerides. Interestingly, fecal elimination of bile acids was increased by some, but not all MSP containing HFDs. Of importance, fecal bile acid, fecal triglyceride, and weight loss was increased in mice treated with 300 or 1,500 mg/kg/day of a top performing MSP via daily oral gavage for 5‐days compared to mice fed HFD given control gavage (H 2 O), although weight loss in the 300 mg/kg group did not achieve the level of statistical significance. The data suggest that MSPs can bind whole intestinal micelles and enhance fecal elimination of bile acids and triglycerides. Taken together, MSPs may serve as a novel weight loss platform for inhibiting excess caloric intake by preventing absorption of dietary triglycerides. Furthermore, increasing fecal elimination of bile acids may also simultaneously serve as a cholesterol lowering agent by increasing de novo bile acid synthesis, a metabolite of cholesterol.