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Title: Diet-induced obesity has a differential effect on adipose tissue and macrophage inflammatory responses of young and old mice

Author
item WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item REN, ZHIHONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item PAE, MUNKYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item HAN, SUNG NIM - Seoul National University
item MEYDANI, SIMINI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Biofactors
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/12/2012
Publication Date: 5/1/2013
Citation: Wu, D., Ren, Z., Pae, M., Han, S., Meydani, S. 2013. Diet-induced obesity has a differential effect on adipose tissue and macrophage inflammatory responses of young and old mice. Biofactors. 39(3):326-333.

Interpretive Summary: Obesity in humans and animals is associated with a low grade, chronic inflammation in body fat tissue. Growing evidence indicates that obesity-associated inflammation contributes greatly to the development of serious chronic diseases including type 2 diabetes, diseases affecting the heart and blood vessels, and conditions that cause deterioration in the nervous system and brain. Additionally, most of these diseases are closely associated with aging. Given these two factors, it is significant to compare age-associated and diet-induced adipose tissue inflammation. Therefore, in the current study, we investigated the effect of age on inflammation in fat tissue in a high fat diet-induced obesity animal model. The results from this study confirmed that aging is associated with increased inflammation; further, we showed that obesity that is developed by consuming high amounts of fat caused inflammation in both the abdominal fat and in macrophages (a type of white blood cell) that reside in the lining of the abdominal cavity in young mice. In contrast, a high fat diet did not further increase inflammation in old mice. Despite this we observed higher mortality in old mice fed high fat diet compared to those fed the control diet. Our results suggest that consuming a high fat diet and the resulting obesity may speed up the aging process in young individuals. Although the aged may not respond to high fat diet as much as the young in terms of weight gain and inflammation, their overall health condition might still be worse, even though it may not be judged by the change in weight and inflammation status. This age-related difference in response to a high fat diet should be considered when using inflammation as an indicator of poor health conditions.

Technical Abstract: Obesity and aging are both associated with increased inflammation in adipose tissue. In this study, we investigated the effect of diet-induced obesity on inflammatory status in young and old mice. Young (2-mo) and old (19-mo) C57BL/6 mice were fed a low fat (10 percent LF) or high fat (60 percent, HF) diet for 4.5 mo. While body weight increased in both age groups, the young mice gained more than the old. All young mice fed LF diet survived to the end of study but in other groups, survival rates were 84.6 percent, 84.6 percent, and 69.2 percent for young/HF, old/LF, and old/HF mice, respectively. Adipose tissue from old/LF mice expressed higher levels of IL-1beta, IL-6, TNF-alpha, and cyclooxygenase (COX)-2 mRNA compared with young/LF mice. HF diet upregulated expression of all these inflammatory markers in young mice to such a level that they showed an inflammatory profile typically seen in the aged. In contrast, these HF diet-induced changes were not observed in old mice. We further found that adipocytes, but not stromal vascular cells, from old LF mice produced more IL-6, TNF-alpha, and prostaglandin (PG)E2 than those from young LF mice. HF diet resulted in an increase of all of these markers produced by adipocytes in young, but only TNF-alpha in old mice. PGE2 produced by peritoneal macrophages was upregulated with aging, and HF diet induced more production of IL-6, TNF-alpha, and PGE2 in young but not in old mice. Thus, obesity induces an inflammatory state in both visceral fat cells and peritoneal macrophages of young mice. Lack of further upregulation of these markers by HF diet in old mice might be due to age-associated impairment in health conditions further deteriorated by HF consumption or inflammation that had already reached maximum levels in old mice and could not increase further. Together, these results suggest that HF-induced obesity may speed up the aging process as characterized by inflammatory status. This result also demonstrates that animals have a differential response, depending on their ages, to HF diet-induced obesity and inflammation. This age-related difference in response to HF diet should be considered when using inflammation status as a marker in investigating adverse health impacts of HF diet and obesity.