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Hepatic steatosis results from several processes. To assess their relative roles, hepatocellular long-chain fatty acid (LCFA) uptake was assayed in hepatocytes from C57BL/6J control mice, mice with steatosis from a high-fat diet (HFD) or 10%, 14%, or 18% ethanol (EtOH) in drinking water [functioning leptin-signaling groups (FLSGs)], and ob/ob and db/db mice. Vmax for uptake was increased vs. controls (P < 0.001) and correlated significantly with liver weight and triglycerides (TGs) in all FLSG mice but was minimally or not increased in ob/ob and db/db mice, in which liver weights and TGs greatly exceeded projections from regressions in FLSG animals. Coefficients of determination (R²) for these FLSG regressions suggest that increased LCFA uptake accounts for ~80% of the increase in hepatic TGs within these groups, but increased lipogenic gene expression data suggest that enhanced LCFA synthesis is the major contributor in ob/ob and db/db. Got2, Cd36, Sic27a2, and Slc27a5 gene expression ratios were significantly upregulated in the EtOH groups, correlating with sterol regulatory element binding protein 1c (SREBP1c) and Vmax, but only Cd36 expression was increased in HFD, ob/ob, and db/db mice. Comparison of Vmax with serum insulin and leptin suggests that both hormones contribute to upregulation of uptake in the FLSG animals. Thus, increased LCFA uptake, reflecting SREBP1c-mediated upregulation of four distinct transporters, is the dominant cause of steatosis in EtOH-fed mice. In ob/ob and db/db mice, increased LCFA synthesis appears more important. In FLSG animals, insulin upregulates hepatocellular LCFA uptake. Leptin appears to upregulate LCFA uptake or to be essential for full expression of upregulation by insulin. [ABSTRACT FROM AUTHOR]

Leptin treatment of ob/ob mice leads to weight loss appreciably greater than that in pair-fed mice. To test whether this "extra" weight loss is mediated by leptin-induced alterations in nutrient partitioning, the effects in ob/ob mice of subcutaneous leptin infusion (500 ng/h for ≤21 d) on adipocyte fatty acid uptake and transporter gene expression were examined. Mice were initially hyperinsulinemic (5.25 ± 1.57 nmol/L). Plasma insulin decreased by 55 ± 10% within 8 h of leptin infusion, declining progressively to normal by d 14. The V[sub max] for saturable adipocyte fatty acid uptake fell from 31.1 ± 5.6 to 25.2 ± 4.0 pmol/(s · 50,000 cells) (P < 0.05) by 24 h, and to a normal rate (8.0 ± 0.8 pmol/(s · 50,000 cells) by d 21 (P > 0.5 vs. normal C57BL/6J controls). Adipocyte mRNA levels for plasma membrane fatty acid binding protein and fatty acid translocase, putative fatty acid transporters that are up-regulated three- to four-fold in adipocytes from ob/ob mice, had also normalized by d 21. The initial changes in V[sub max] preceded decreases in food intake and body weight by at least 24 h. In pair-fed mice, insulin levels, V[sub max] and body weight all declined more slowly than in leptin-treated mice, and all remained significantly elevated compared with normal values at d 21. The data suggest that insulin up-regulates and leptin down-regulates adipocyte fatty acid uptake, leading to alterations in fatty acid partitioning that affect adiposity. [ABSTRACT FROM AUTHOR]

Radio-labeled conjugated bilirubin was purified from rat bile by affinity chromatography. Following the intravenous injection of tracer doses of this material, the initial fractional plasma disappearance rate of conjugated bilirubin-³H in the normal Sprague-Dawley rat was found to be approximately 50% faster than that for unconjugated bilirubin-³H (0.51 ± 0.04 [SE] vs. 0.35 ± 0.02 min.-1; P < .001 ). Hepatic recovery studies in the rat indicated that, over the first four minutes after injection, disappearance of cholephilic anions from plasma is accounted for almost entirely by hepatic uptake. Hence, these studies demonstrate that hepatic uptake of conjugated bilirubin is substantially faster than that of unconjugated bilirubin. Net hepatic clearance of conjugated bilirubin in normal rats was three-fold greater than that of unconjugated bilirubin (0.94 ± 0.16 vs. 0.30 ± 0.03 ml./min./100 gm. body weight; P < .001), presumably reflecting both the more rapid hepatic uptake and the ability of the former pigment to by-pass the conjugation step. Hepatic uptake of conjugated bilirubin was shown to be inhibited by unconjugated bilirubin, sulfobromophthalein and indocyanine green but not by glycocholate. These observations cannot be explained by simple diffusion and suggest that the hepatic uptake mechanism for conjugated bilirubin is the same as that for the unconjugated pigment. [ABSTRACT FROM AUTHOR]

Focuses on a conference on fulminant hepatic failure co-sponsored by the National Institute of Arthritis, Metabolism and Digestive Diseases and the John E. Fogarty International Center of the National Institutes of Health in Bethesda, Maryland in February 1977. Topics discussed at the conference, including liver cell necrosis and organelle dysfunction; Speakers at the conference; Background on acute fulminant hepatic failure.

Discusses various approaches to reduce plasma bilirubin concentration in unconjugated hyperbilirubinemia. Advantages of reducing bilirubin concentration by accelerating heptic bilirubin clearance or decreasing plasma bilirubin turnover; Possibility of detecting Gilbert's syndrome in the presence of concomitant hemolysis; Bilirubin encephalopathy development in the case of Crigler-Najjar syndrome.

Presents a study that determined the disappearance rate of plasma bilirubin-[sup14]C specific activity. Information on a multicompartmental model of bilirubin metabolism; Analysis of methods used for determining the plasma bilirubin [sup14]C specific activity; Calculation of the intercompartmental rate constants and bilirubin production rate.