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Title: LEPTIN, TUMOR NECROSIS FACTOR (TNF)-A, AND CD-14 IN OVINE ADIPOST TISSUE AND CHANGES IN CIRCULATING TNF IN LEAN AND OBESE SHEEP

Author
item DANIEL, J. - SOUTH DAKOTA STATE UNIV
item Elsasser, Theodore
item MORRISON, C. - UNIVERSITY OF MISSOURI
item KEISLER, D. - UNIVERSITY OF MISSOURI
item WHITLOCK, B. - AUBURN UNIVERSITY
item STEELE, B. - AUBURN UNIVERSITY
item PUGH, D. - AUBURN UNIVERSITY
item SARTIN, J. - AUBURN UNIVERSITY

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/13/2003
Publication Date: 10/1/2003
Citation: Daniel, J., Elsasser, T.H., Morrison, C., Keisler, D., Whitlock, B., Steele, B., Pugh, D., Sartin, J. 2003. Journal of Animal Science. 81(10):2590-2599.

Interpretive Summary: Severe metabolic responses occur in response to animals developing infections and stress. When animals do encounter illness, there developes a set of complex interactions that alter heat production, nutrient use and the breakdown of fat and muscle to provide energy for the animal. In addition, the infected animals tend to decrease food intake. The experiments described here indicate that fat tissue and body composition may affect how animals respond to infection. The results provide evidence that both CD14 ( the cell receptor that permits it to respond to bacterial toxins) and TNF (an immune hormone the stimulated fat and muscle breakdown) are produced by fat tissue in sheep, and with other reports, suggest that the fat tissue may have a role in immune response. Additionally circulating levels of TNF are affected by obesity, suggesting an additional mechanism for the fat cell to signal body condition.

Technical Abstract: Four studies were designed to assess the interactions between lipopolysaccaride (LPS), leptin, and inflammatory cytokines, tumor necrosis factor-a (TNF) and interleukin-1b (IL-1). For experiments 1 and 2, ewes were assigned, based on ultrasonic assessments of last-rib subcutaneous fat measurements into fat or thin groups. Fat- and thin-ewes were assigned to fed or fasted groups for a total of 4 groups (fed-fat; fasted-fat; fed-thin; fasted-thin). Fed-ewes had ad libitum access to feed and fasted-ewes were prohibited feed 48 h prior to initiation of the experiment. In experiment 1, subcutaneous fat samples were collected from just above the last rib for detection of TNF, CD14, and leptin. TNF-like immunoreactivity in adipocytes was sparse, more pronounced in cells in fed-ewes than fasted-ewes, and localized to membrane between adjacent cells in nucleated regions. CD14 was minimally observed, but present in adipocytes and widely expressed in infiltrating monocytes and epithelial vascular cells. Leptin was detected in adipocytes. In experiment 2, plasma samples collected every 6 h for 24 h were analyzed for plasma concentrations of TNF, glucose, NEFA, and leptin. Fed-ewes had greater plasma concentrations of glucose (P <0.04) as well as lower plasma concentrations of NEFA (P = 0.0001) than fasted-ewes. Fat-ewes had greater plasma concentrations of TNF than thin-ewes (P < 0.04). In experiment 3, wethers were challenged iv with IL-1 and TNF. Blood samples were collected every 15 minutes for 8 hours following challenge. Plasma concentration of leptin was not effect by treatment. In experiment 4, wethers were challenge with LPS. Plasma concentration of leptin was not altered by LPS. These data suggest the presence of TNF-like immunoreactivity within fat tissue and that elements within fatty tissue have CD14 to allow for possible direct response to LPS affecting adipocyte function. Moreover, these data indicate that circulating levels of TNF are increased with obesity in sheep.