The Angiogenic Inhibitor TNP‐470 Decreases Caloric Intake and Weight Gain in High‐Fat Fed Mice

• Published in: Obesity (Silver Spring, Md.) Md.), 2012-10, Vol.20 (10), p.2003-2009
• Main Authors: White, Heather M., Acton, Anthony J., Considine, Robert V.
• Format: Article
• Language: English
• Subjects: Absorptiometry, Photon; Adiposity - drug effects; Angiogenesis; Angiogenesis Inhibitors - pharmacology; Animals; Area Under Curve; Blood Glucose - metabolism; Cyclohexanes - pharmacology; Diet, High-Fat; Energy Intake - drug effects; Energy Metabolism - drug effects; Glucose Tolerance Test; Inhibitor drugs; Mice; Mice, Inbred C57BL; Obesity; Obesity - prevention & control; Rodents; Sesquiterpenes - pharmacology; Weight Gain - drug effects
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1038/oby.2012.87

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.