title: The angiogenic inhibitor TNP-470 decreases caloric intake and weight gain in high-fat fed mice.
abstract: The angiogenic inhibitor TNP-470 attenuates high-fat diet-induced obesity; however, it is not clear how the compound alters energy balance to prevent weight gain. Five-week-old C57BL/6J mice were fed high-fat diet (45% energy from fat) for 6.5 weeks and treated with TNP-470 (20 mg/kg body weight; n = 7) or vehicle (saline; n = 7). Control mice (n = 8) received standard chow and sham injection. TNP-470 mice initially gained weight, but by day 5 body weight was significantly less than high-fat fed (HFF) mice and not different from that of chow-fed mice, an effect maintained to the end of the study (28.6 ± 0.6 vs. 22.4 ± 0.6 and 22.2 ± 0.5 g). Percent body fat was reduced in TNP-470 compared to HFF mice, but was greater than that of chow mice (34.0 ± 1.5, 23.9 ± 1.5, and 17.0 ± 1.4%, P < 0.05). Food intake in TNP-470-treated mice was less (P < 0.05) than that in HFF mice by day 5 of treatment (2.5 ± 0.1 vs. 2.8 ± 0.1 g/mouse/day) and remained so to the end of the study. Twenty-four hours energy expenditure was greater (P < 0.05) in TNP-470 than HFF or chow mice (7.05 ± 0.07 vs. 6.69 ± 0.08 vs. 6.79 ± 0.09 kcal/kg/h), an effect not explained by a difference in energy expended in locomotion. Despite normalization of body weight, TNP-470 mice exhibited impaired glucose tolerance (area under the curve 30,556 ± 1,918 and 29,290 ± 1,584 vs. 24,421 ± 903 for TNP, HFF, and chow fed, P < 0.05). In summary, the angiogenic inhibitor TNP-470 attenuates weight gain in HFF mice via a reduction in caloric intake and an increase in energy expenditure.
authors.affiliation: Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: White
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Acton
authors.forename: Robert V
authors.initials: RV
authors.lastname: Considine
mesh_terms: D015502:Absorptiometry, Photon; D050154:Adiposity / Q000187:drug effects*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D003510:Cyclohexanes / Q000494:pharmacology*; D059305:Diet, High-Fat; D002149:Energy Intake / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D005951:Glucose Tolerance Test; D051379:Mice; D008810:Mice, Inbred C57BL; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D009765:Obesity / Q000517:prevention & control*; D012717:Sesquiterpenes / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D020533:Angiogenesis Inhibitors; D001786:Blood Glucose; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol