Acinar heterogeneity of fatty acid binding protein... : Hepatology (original) (raw)

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Acinar heterogeneity of fatty acid binding protein expression in the livers of male, female and clofibrate-treated rats†

Bass, Nathan M. M.D., Ph.D.*, 1; Barker, Mary E.1; Manning, Joan A.1; Jones, Albert L.1; Ockner, Robert K.1

1Departments of Medicine and Anatomy and the Liver Center, University of California, San Francisco, California 94143, and Cell Biology Section, Veterans Administration Hospital, San Francisco, California 94121

*Address reprint requests to: Department of Medicine and Liver Center, Box 0538, HSW 1120, University of California, San Francisco, California 94143.

Received September 09, 1987; Accepted June 28, 1988; previously published online December 05, 2005

†The results of this work were presented in part at the 36th Annual Meeting of the American Association for the Study of Liver Diseases, Chicago, Illinois (1985), and appeared in abstract form (Hepatology 1985; 5:1011).

Abstract

Liver fatty acid binding protein may play a role in the intracellular transport and compartmentation of long-chain fatty acid metabolism. The distribution of liver fatty acid binding protein in the hepatic acinus was determined by means of immunocytochemistry as well as by measurement of liver fatty acid binding protein in cellular protein selectively released from zone 1 and zone 3 cells by means of anterograde and retrograde liver perfusion with digitonin. In untreated male rats, specific immunocytochemical staining for liver fatty acid binding protein showed a declining portal-to-central hepatocellular gradient in intensity, consistent with the portal-to-central ratio of liver fatty acid binding protein abundance measured in effluents from digitonin-perfused livers of 1.6:1. Female and clofibratetreated male rats, in both of which hepatic synthesis and abundance of liver fatty acid binding protein are greater than in untreated males, differed as well in the pattern of acinar expression of this protein. In females, periportal concentrations of liver fatty acid binding protein determined from the effluent of livers perfused anterograde with digitonin were similar to male values, whereas liver fatty acid binding protein concentration in pericentral hepatocytes determined from the effluent of retrograde perfused livers was increased, resulting in a marked attenuation of the portal-to-central gradient of this protein; this was also apparent on immunocytochemistry. Clofibrate-treated rats, in contrast, displayed a panacinar increase in liver fatty acid binding protein with maintenance of the portal-to-central ratio observed in untreated males. We conclude that there exists a declining portal-to-central gradient in liver fatty acid binding protein cellular abundance in the hepatic acinus of untreated male rats. Furthermore, the increased synthesis and abundance of liver fatty acid binding protein in female and clofibrate-treated male rats results in two different alterations in the acinar expression of this protein, i.e. a pericentral increase (female) or a panlobular increase (clofibrate). Elucidation of the relationship between the zonation of hepatic fatty acid metabolism and the acinar expression of liver fatty acid binding protein should provide a more detailed understanding of the function of this protein.