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Inflammation plays a major role in the development of chronic diseases such as cardiovascular disease and Type 2 diabetes. Further, it was demonstrated that obese animals and humans have significantly higher levels of circulating proinflammatory cytokines, such as interleukin-6 (IL-6). The aim of this study was to determine whether adipose tissue could be a major source of circulating IL-6 in leptin-deficient obese (ob/ob) mice by comparing the expression of IL-6 in different tissues of ob/ob mice. Our secondary goal was to determine whether preadipocytes are the source of adipose tissue IL-6. The ob/ob mice had higher levels of plasma IL-6 (P < 0.05) and adipose tissue IL-6 mRNA (P < 0.05) compared with lean mice. Interestingly, IL-6 mRNA levels of liver and spleen were not different between ob/ob and lean mice, whereas adipose tissue IL-6 mRNA levels were higher in the ob/ob mice compared with lean mice (P < 0.05). In addition, we showed that IL-6 secretion from the adipose tissue stromal vascular fraction cells was higher than that from fully differentiated adipocytes (P < 0.001). We further demonstrated that 3T3-L1 preadipocytes had significantly higher levels of lipopolysaccharide (LPS)stimulated IL-6 mRNA and IL-6 secretion than differentiated 3T3-L1 adipocytes. Taken together, these data suggest that adipose tissue and preadipocytes from the adipose tissue stromal vascular fraction may contribute significantly to the increased plasma IL-6 levels in ob/ob mice. KEY WORDS: * interleukin-6 * preadipocyte * obesity

Naphthenic acids (NAs) are primarily cycloaliphatic carboxylic acids with 10 to 16 carbons. To characterize the potential of refined NAs (>70% purity) to cause reproductive and/or developmental effects, Sprague-Dawley rats (12/group) were given oral doses of 100, 300, or 900 mg/kg/d, beginning 14 days prior to mating, then an additional 14 days for males or through lactation day 3 for females (up to 53 days) in a repeated dose/reproductive toxicity test (Organization for Economic Cooperation and Development [OECD] 422). Potential mutagenic effects were assessed using Salmonella (OECD 471) and in in vivo micronucleus tests (OECD 474) using bone marrow taken from treated animals in the screening study described previously. Systemic effects included reduced terminal body weights, increased liver weights, and changes in a number of blood cell parameters. The overall no effect level for all target organ effects was 100 mg/kg/d. In the reproductive/developmental toxicity assessment, there were significant reductions in numbers of live born offspring in groups exposed to 300 and 900 mg/kg/d. The overall no effect level for developmental effects was 100 mg/kg/d. The data from the Salmonella and micronucleus tests provide evidence that refined NAs are not genotoxic. [ABSTRACT FROM AUTHOR]