Study of hepatic binding protein activity in jejuno-ileal by-passed rat hepatocytes.

The kinetic constants of internalization of asialoorosomucoid were determined for normal and jejuno-ileal by-passed rat hepatocytes. In by-passed rats the maximum velocity of asialoorosomucoid internalization is decreased 3-fold, without any modification of apparant constant of internalization. Moreover, the rate constant of internalization was the same in the two groups of rats. These data suggest that the process of asialoorosomucoid internalization is not altered in by-passed hepatocytes and that the decrease of maximal velocity is only due to a decrease of total uptake receptor number.

[Fructose utilization by hepatocytes isolated from fed obese fa/fa Zucker rats. Metabolic fate of fructose in the absence of the modulator]. / Utilisation du fructose par l'hépatocyte isolé de rat nourri Zucker obèse fa/fa. I. Orientation métabolique du fructose en l'absence de modulateur.

The utilization of fructose by isolated hepatocytes was investigated in fed obese Zucker fa/fa rats compared with their lean littermates (Fa/?) and Sprague-Dawley rats. Hepatocytes were incubated during 3 h using U14C fructose (20 mM). Our results show: a significant increase of fructose consumption, glucose, lactate and pyruvate production and faster turnover of glycogen by fa/fa rats. In these animals, synthesis of acylglycerol was also significantly enhanced. Our results suggest that fructose in fa/fa rats was used preferentially as precursor for lipid synthesis not only by the liver but also by the adipose tissue after a prior transformation into glucose by hepatocytes. All these abnormalities result in an accumulation of acylglycerols maintaining an obesity state in fa/fa rats.

Lipogenesis from U14C lactate in obese Zucker rat hepatocytes. Effect of albumin-bound oleate.

Lipogenesis from U(14C) lactate was studied in hepatocytes isolated from obese Zucker rats (fa/fa) their lean littermates (Fa/?) and Sprague Dawley rats. The distribution of radioactive carbon between the glycerol and the fatty acid moieties of the acylglycerols were studied. Radioactive lactate was better utilized for glycerol formation than it was for fatty acid formation in the obese rats. However, when oleate was added to the hepatocytic incubation medium, radioactive lactate was preferentially incorporated into the fatty acid moiety of the acylglycerols. Zucker obesity classified as a "metabolic obesity" by Meyer (1) depends upon abnormalities in carbohydrate metabolism associated with increased lipogenesis. This might be explained by biochemical shifts in the utilization of nutrients (2). Among the nutrients, lactate seems to be a better source of carbon than glucose for lipid synthesis (3). It has been shown that there is an increased hepatic portal blood concentration of lactate several hours after eating: about 4 mM in Wistar rats (4) and 10-15 mM in obese Zucker rats (3). We are interested in determinating the incorporation of carbon from lactate either into glycerol or into fatty acyl moieties of hepatic acylglycerols, and in determining the influence of exogenous fatty acids on acylglycerol synthesis, since a high level of circulating fatty acids in Zucker obese rats has been reported (5). Our purpose was to determine the incorporation of lactate into glycerol and fatty acyl moieties of acylglycerols, under the influence of oleate. Hepatocytes were isolated from ad libitum fed obese Zucker rats (fa/fa), their lean littermates (Fa/?) and Sprague-Dawley rats (SD). Incorporation of lactate was studied for three hours, in order to exclude short-term regulation effects and to allow oleate to be distributed into all cellular compartments.

Measurement of serum alpha 1-acid glycoprotein and alpha 1-antitrypsin desialylation in liver disease.

To determine whether the presence of circulating desialylated glycoproteins reflect the existence and/or the severity of liver disease, 73 patients were evaluated with liver biopsies, conventional liver function tests, and the measurement of the degree of desialylation of two glycoproteins alpha 1-acid glycoprotein (alpha 1-AGP) and alpha 1-antitrypsin (alpha 1-AT). A combination of two immunological methods, available as routine laboratory tests, was used for the determination of the desialylation of alpha 1-AGP and alpha 1-AT. The severity of liver disease was assessed by a clinical classification depending upon the presence or absence of four complications (jaundice, ascites, hepatic encephalopathy, and weight loss). The presence of serum desialylated alpha 1-AGP did not allow detection of mild liver disease, but asialo alpha 1-AGP (and to a lesser extent of asialo-alpha 1-(AT) correlated with the severity of liver disease. The sensitivity of desialylated alpha 1-AGP in detection of severe liver disease was 65%, and its specificity was 80%.

Evaluation of the degree of desialylation of serum alpha 1-acid glycoprotein and alpha 1-antitrypsin.

A method for evaluating the degree of desialylation of alpha 1-AGP and alpha 1-AT has been developed. It consists in their simultaneous determination by radial immunodiffusion (RID) and electroimmunodiffusion (EID). When a desialylation exists, an underestimation by EID relative to RID is found. (1) No significant desialylation of alpha 1-AGP and alpha 1-AT occurred in normal subjects. (2) No correlation between desialylation of alpha 1-AGP and alpha 1-AT and their amounts existed. (3) Desialylation was preferentially observed in patients with severe hepatic damage but also with inflammatory disorders.