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High Fat Diets Elevate Adipose Tissue-Derived Tumor Necrosis Factor- Activity¹

University of Colorado Health Sciences Center, Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine (C.L.M., R.H.E., T.M.), Department of Pediatrics (M.J.P.), and Center for Human Nutrition (C.L.M., R.H.E., M.J.P.), Denver, Colorado 80262

Address all correspondence and requests for reprints to: Catherine Morin, University of Colorado Health Sciences Center, 4200 East 9th Avenue, C225, Denver, Colorado 80262. E-mail: Catherine.Morin{at}uchsc.edu

Adipose tissue-derived tumor necrosis factor- (AT-TNF) has been associated with genetic models of insulin resistance and obesity. It is presently unknown if secreted AT-TNF protein is bioactive or whether it can be increased by environmentally induced obesity. In this study, male Wistar rats were fed either a low fat (LF; 12% of energy from corn oil) or a high fat (HF; 45% of energy from corn oil) diet for 5 weeks. From previous data, it is known that after 3 weeks, HF fed animals are obese and insulin resistant compared with the LF group. Hence, animals were killed at 1 week of HF feeding, during the acute response to the diet, and at 5 weeks, when differences in body fat are manifest. Weight gain was significantly increased by diet (P = 0.03) and time (P < 0.0001). AT-TNF bioactivity was measured on secreted protein collected from medium of minced, incubated epididymal (EPI), mesenteric (MES), and retroperitoneal (RETRO) fat pads. AT-TNF bioactivity was significantly increased by diet (P = 0.003) in the RETRO pad and tended to increase (P = 0.07) in EPI. AT-TNF activity was unaffected by diet or time in the MES pad. In the RETRO pad, TNF activity correlated negatively with RETRO fat cell number (r = -0.46, P = 0.002). Secreted AT-TNF protein did not correlate with AT-TNF activity but instead decreased in RETRO with time but not diet. In EPI, secreted AT-TNF protein decreased with the HF diet. Thus, these data suggest that high fat diets and obesity can influence AT-TNF bioactivity and secretion but in an apparent fat pad-specific manner.

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