The relationship between liver peroxisome proliferation and adipose tissue atrophy induced by peroxisome proliferator exposure and withdrawal in mice.
We have previously demonstrated that severe adipose tissue atrophy occurs upon dietary treatment of mice with potent peroxisome proliferators (PPs). This atrophy occurs subsequent to peroxisome proliferation in the liver and may represent a novel addition to the pleiotropic effects exerted by PPs. In the present study we have characterized the recovery of mice from such atrophy following cessation of exposure. Following termination of treatment with perfluorooctanoic acid (PFOA) for 7 days, the adipose tissue atrophy was rapidly reversed, beginning on 2-5 days of recovery and being complete within 10 days. In contrast, hepatic peroxisome proliferation recovered much more slowly, indicating that these processes are not strictly coordinated. Analysis of lipoprotein lipase and hormone-sensitive lipase activities in adipose tissue revealed that the decrease and increase in these activities, respectively, caused by PFOA were both reversed within 10 days of recovery. Overall, these data provide further support for our previous conclusion that the adipose tissue atrophy induced by PFOA is caused, at least in part, by changes in the activities of lipoprotein lipase and hormone-sensitive lipase. The serum level of cholesterol, which increased after termination of PFOA treatment, returned to normal with a time-course similar to the recovery of adipose tissue weight, although hepatic peroxisome proliferation was still present. The possible relationship between the reduction in serum cholesterol and/or in its availability to peripheral tissues and the associated atrophy of adipose tissues caused by PPs is discussed.
Xie
Yi
Y
Unit for Biochemical Toxicology, Wallenberg Laboratory, Department of Biochemistry and Biophysics, Stockholm University, S-106 91 Stockholm, Sweden. yi@dbb.su.se
Yang
Qian
Q
Nelson
B Dean
BD
DePierre
Joseph W
JW
D000273:Adipose Tissue / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D001053:Apolipoproteins / Q000097:blood; D002210:Caprylates / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology; D005227:Fatty Acids / Q000378:metabolism; D005466:Fluorocarbons / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D020675:Peroxisomes / Q000187:drug effects* / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000378:metabolism*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D001053:Apolipoproteins; D002210:Caprylates; D005227:Fatty Acids; D005466:Fluorocarbons; D008055:Lipids; D020025:Peroxisome Proliferators; D014280:Triglycerides; C023036:perfluorooctanoic acid; D002784:Cholesterol; D008071:Lipoprotein Lipase