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Title: Differential effect of weight loss with low-fat diet or high-fat diet restriction on inflammation in the liver and adipose tissue of mice with diet-induced obesity

Author
item WANG, QUN - Baylor College Of Medicine
item PERRARD, XIAOYUAN - Baylor College Of Medicine
item PERRARD, JERY - Baylor College Of Medicine
item MANSOORI, AMIR - Baylor College Of Medicine
item RAYA, JOE - Baylor College Of Medicine
item HOOGEVEEN, RON - Baylor College Of Medicine
item SMITH, C - Children'S Nutrition Research Center (CNRC)
item BALLANTYNE, CHRISTIE - Children'S Nutrition Research Center (CNRC)
item WU, HUAIZHU - Children'S Nutrition Research Center (CNRC)

Submitted to: Atherosclerosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/7/2011
Publication Date: 7/21/2011
Citation: Wang, Q., Perrard, X.D., Perrard, J.L., Mansoori, A., Raya, J.L., Hoogeveen, R., Smith, C.W., Ballantyne, C.M., Wu, H. 2011. Differential effect of weight loss with low-fat diet or high-fat diet restriction on inflammation in the liver and adipose tissue of mice with diet-induced obesity. Atherosclerosis. 219(1):100-108.

Interpretive Summary: The beneficial effect of weight loss in obese individuals was tested in obese mice. Obesity was induced by feeding a high fat diet for 6 months. Then, weight loss was caused by changing the diet, either switching to a normal low fat diet or restricting the amount of the high fat diet. One month after beginning the weight loss diets, the normal low fat diet was more effective in protecting the liver from the injurious effects of obesity, and the restricted high fat diet was more effective in reducing tissue inflammation caused by obesity. These findings underscore the beneficial effects of weight loss, and emphasize the need for additional study to define the most comprehensive approach to weight loss.

Technical Abstract: We studied the effects of weight loss induced by either a low-fat normal diet or restriction of high-fat diet on hepatic steatosis, inflammation in the liver and adipose tissue, and blood monocytes of obese mice. In mice with high-fat diet-induced obesity, weight loss was achieved by switching from high-fat diet to normal diet and maintaining on normal diet ad libitum or by restricting high-fat diet intake to match body weight of mice with normal diet-induced weight loss. After diet interventions for 4 weeks, hepatic steatosis, hepatic and adipose tissue inflammation, and blood CD11c+ monocytes were examined. At 4 weeks after switching diets, body weight was reduced by 23% from baseline. To achieve the same reduced body weight required restricting calorie intake from high-fat diet. Weight loss with either normal diet or high-fat diet restriction decreased body fat mass and ameliorated liver steatosis; both effects were greater with normal diet-induced weight loss than high-fat diet restriction–induced weight loss. Weight loss with normal diet but not high-fat diet restriction normalized blood CD11c+ monocytes and attenuated hepatic inflammation assessed by chem and CD11c expression. In contrast, weight loss with high-fat diet restriction significantly reduced chemokine levels and CD11c+ cells in adipose tissue compared to obese controls, and tended to reduce adipose tissue chemokines and CD11c+ cells more than normal diet-induced weight loss. In mice with diet-induced obesity, weight loss with normal diet was superior in alleviating hepatic inflammation and steatosis, whereas weight loss with high-fat diet calorie restriction provided greater amelioration of adipose tissue inflammation.