EFFECT OF BILE-ACID COMPOSITION AND MANIPULATION OF ENTEROHEPATIC CIRCULATION ON LEPTIN GENE-REGULATION

In the rat, the ob gene product, leptin, putatively regulates energy b alance via appetite control and energy expenditure. Bile acids in the intestinal lumen are necessary for efficient absorption of dietary lip ids and may trigger the release of regulatory peptides. To investigate whether bile acids play a role in leptin gene expression, we altered the bile acid pool and then measured leptin mRNA levels in adipose tis sue. Rats fed cholic acid (1% of chow wt/wt) for 2 weeks did not gain weight as rapidly as pair-fed control animals. Despite the lower weigh t, normalized leptin mRNA levels were 24% greater in cholic acid-fed r ats compared with controls. Conversely, cholestyramine, a bile acid se questrant, in chow (5% wt/wt) resulted in a 26% decline in leptin mRNA . Ligation of the common bile duct or chronic biliary diversion, exper imental manipulations that decreased the intestinal concentration of b ile salts, decreased leptin gene expression by 30% and 50%, respective ly. A fluid and electrolyte (F/E) solution with and without taurochola te (36 mu mol/h.100 g rat(-1)) was then infused for 12 hours into the duodenum in animals with chronic biliary diversion. Taurocholate infus ion resulted in a fourfold increase in steady-state adipocyte leptin m RNA levels compared with F/E infusion. Intravenous infusion of tauroch olate or incubation of cultured adipocytes with taurocholate had no ef fect on leptin mRNA levels. We conclude that bile acids upregulate lep tin gene expression indirectly, probably via effects on the absorption of dietary lipids or the release of neurohumoral mediators. Copyright (C) 1998 by W.B. Saunders Company.