Brown adipose tissue distribution

High concentrations of radioactivity were observed in body fat and livers of rats, mice, and squirrel monkeys given oral doses of 60 mg/kg " C-labeled chloroform (Brown et al. 1974a). The maximum levels of radioactivity in the blood appeared within 1 hour and were 3 pg equivalents chloroform/mL for mice and 10 pg equivalents chloroform/mL for monkeys, which represented -0.35 and 1%, respectively, of the total radioactivity. In monkeys, bile concentrations peaked within 6 hours. The distribution of radioactively labeled chloroform was studied in three strains of mice (Taylor et al. 1974). No strain-related differences were observed however, higher levels of radioactivity were found in the renal cortex of males and in the liver of females. The renal binding of radioactive metabolites may have been altered by variations in the testosterone levels as a result of hormonal pretreatment in females or castration in males. Sex-linked differences in chloroform distribution were not observed in rats or monkeys (Brown et al. 1974a). Chloroform accumulates in the adipose tissue of rats after oral exposure of intermediate duration (Pfaffenberger et al. 1980). 

The first PPAR was reported by Issemann and Green30 in rodents. To date, three distinct PPARs, encoded by three distinct genes have been identified PPARa, PPAR/3, and PPARy. These isoforms have different tissue distributions, with PPARa expressed primarily in liver, heart and kidney, PPARy in brown and white adipose tissues, and PPAR/3 (also known as 8) is more ubiquitously expressed, but most abundant in the central nervous system14,17,35. The role of each isoform is beyond the scope of this review as fibrate drugs are mainly PPARa-ligands14, only this form will be examined in detail here. Nevertheless, it should be mentioned that isoforms of the PPAR family have now been cloned from Xenopus laevis, a number of mammals49,50, as well as in some fish species1. 

Information on toxic effects of acute-duration exposure to PCBs by routes other than oral are limited to LD50 values for dermal exposure (Fishbein 1974 Puhvel et al. 1982), but these data may not be reliable due to possible delayed lethality. PCBs are well absorbed after exposure by all routes, and distribution to and retention by adipose tissue has been observed in humans after inhalation, oral, and/or dermal exposure (Brown and Lawton 1984 Fait et al. 1989 Jensen 1987). Mobilization of PCBs from adipose tissue to target organs is likely to be similar regardless of the route of exposure. Additional acute dermal studies are relevant because the skin is a route of concern for exposure at or near hazardous waste sites, particularly due to possibilities for brief contact. Acute inhalation toxicity studies may be relevant due to the potential for inhalation exposure from electrical appliances in buildings and downwind from PCB disposal facilities and incinerators. 

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