Lipogenic Hypercholesteremia

Friedman, Meyer

doi:10.1001/archinte.1965.03870060005001

Cited by 5 publications

(2 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It may be presumed that the initial hypercholesterolemia was of the lipogenic or tri¬ glycéride induced type as recently described by Friedman et al 17 These authors support¬ ed their earlier premise18 that excess triglyc¬ éride in plasma effects a physicochemical sequestration into the plasma of excess cho¬ lesterol. It is therefore of interest that choles¬ tyramine (16 gm per day) initially induced a decrease in serum cholesterol without a concomitant diminution in the serum tri¬ glycéride levels.…”

Section: Second Hospital Admissionsupporting

confidence: 54%

Essential Hyperlipemia With Xanthomatosis

Roe¹

1968

Arch Dermatol

View full text Add to dashboard Cite

Section: Second Hospital Admissionsupporting

confidence: 54%

Essential Hyperlipemia With Xanthomatosis

Roe¹

1968

Arch Dermatol

View full text Add to dashboard Cite

“…MTP protein levels were increased ϳ1.7-fold (p Ͻ 0.025) in CYP7A1 transgenic mice compared with non-transgenic littermates when normalized to protein-disulfide isomerase (data not shown). (40). The rate of accumulation of VLDL in plasma following intravenous injection of Triton WR-1339 therefore provides a means to estimate their production rates.…”

Section: Transgenic Expression Of Cyp7a1 Increases the Hepatic Expresmentioning

confidence: 99%

Increased Production of Apolipoprotein B-containing Lipoproteins in the Absence of Hyperlipidemia in Transgenic Mice Expressing Cholesterol 7α-Hydroxylase

Miyake

Doung

Strauss

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

The finding that expression of a cholesterol 7␣-hydroxylase (CYP7A1) transgene in cultured rat hepatoma cells caused a coordinate increase in lipogenesis and secretion of apoB-containing lipoproteins led to the hypothesis that hepatic production of apoB-containing lipoproteins may be linked to the expression of CYP7A1 (Wang, S.-L., Du, E., Martin, T. D., and Davis, R. A. (1997) J. Biol. Chem. 272, 19351-19358). To examine this hypothesis in vivo, a transgene encoding CYP7A1 driven by the constitutive liver-specific enhancer of the human apoE gene was expressed in C56BL/6 mice. The expression of CYP7A1 mRNA (20-fold), protein (ϳ10-fold), and enzyme activity (5-fold) was markedly increased in transgenic mice compared with non-transgenic littermates. The bile acid pool of CYP7A1 transgenic mice was doubled mainly due to increased hydrophobic dihydroxy bile acids. In CYP7A1 transgenic mice, livers contained ϳ3-fold more sterol response element-binding protein-2 mRNA. Hepatic expression of mRNAs encoding lipogenic enzymes (i.e. fatty-acid synthase, acetyl-CoA carboxylase, stearoyl-CoA desaturase, squalene synthase, farnesylpyrophosphate synthase, 3-hydroxy-3-methylglutarylCoA reductase, and low density lipoprotein receptor) as well as microsomal triglyceride transfer protein were elevated ϳ3-5-fold in transgenic mice. CYP7A1 transgenic mice also displayed a >2-fold increase in hepatic production and secretion of triglyceride-rich apoB-containing lipoproteins. Despite the increased hepatic secretion of apoB-containing lipoproteins in CYP7A1 mice, plasma levels of triglycerides and cholesterol were not significantly increased. These data suggest that the 5-fold increased expression of the low density lipoprotein receptor displayed by the livers of CYP7A1 transgenic mice was sufficient to compensate for the 2-fold increase production of apoB-containing lipoproteins. These findings emphasize the important homeostatic role that CYP7A1 plays in balancing the anabolic lipoprotein assembly/secretion pathway with the cholesterol catabolic bile acid synthetic pathway.Hepatic lipoprotein secretion requires apoB having a size that is sufficiently large to allow the formation of a lipoprotein particle containing a neutral lipid core, the availability of lipids (i.e. phospholipids, triglycerides, cholesterol, and cholesterol esters), and the intraluminal chaperone/lipid transfer protein microsomal triglyceride transfer protein (MTP) 1 (reviewed in Refs. 1-6). The assembly of apoB-containing lipoproteins is abrogated when these essential requirements are not satisfied, resulting in rapid degradation of apoB within the hepatocyte (7). The most characterized pathway responsible for the rapid, co-translational degradation of incompletely translocated apoB is via a ubiquitin-dependent proteasome process (8 -11). Several additional pathways that may contribute to the intracellular degradation of apoB have been described (12)(13)(14)(15).Cholesterol 7␣-hydroxylase (CYP7A1) is a liver-specific enzyme that regulates the production of bil...

show abstract

Studien zur Charakterisierung und zum Stoffwechsel des Lipoprotein-X (LP-X), des abnormen Lipoproteins der Cholestase

Seidel¹

1977

Klin Wochenschr

View full text Add to dashboard Cite

Recent results regarding the pathophysiology of hyperlipoproteinemia in cholestasis are reported. The isolation of an abnormal lipoprotein (Lipoprotein-X; LP-X) from the plasma of cholestatic patients was achieved by a combination of various physico-chemical techniques. Most of the plasmacholesterol in these patients is transported in form of this abnormal lipoprotein which is very rich in phospholipids and unesterfied cholesterol. LP-X represents a vesicle with a mean diameter of 700 A. Albumin takes part as a structural protein of the particle. Besides albumin, which seems to be located in an internal water compartment or to be covered with lipids. Apo-C and Apo-D are present as surface proteins. The lack of Apo-B in LP-X, the major apoprotein of normal low density lipoproteins, seems to be the reason for a disturbed endogenous feedback mechanism of hepatic cholesterol synthesis, which is strongly increased in cholestasis. The high specificity and power of the LP-X test as clinical-chemical parameter to demonstrate or exclude cholestasis finds its explanation in our knowledge about the origin of this abnormal lipoprotein in cholestasis. LP-X is formed when a lipoprotein normally excreted with the bile refluxes into the plasma stream to convert into LP-X. This formation depends only on certain physico-chemical requirements and is independent of an energy-providing or enzymatically regulated process. The biological halflife of LP-X is similar to that of normal plasmalipoproteins. However, enzymes of postheparin plasma as well as the lecithin: cholesterol acyltransferase do not seem to play a major role in the catabolism of lipoprotein-X, but only change some of the physicochemical characteristics of this vesicle.

show abstract

Lipogenic Hypercholesteremia

Cited by 5 publications

References 2 publications

Essential Hyperlipemia With Xanthomatosis

Essential Hyperlipemia With Xanthomatosis

Increased Production of Apolipoprotein B-containing Lipoproteins in the Absence of Hyperlipidemia in Transgenic Mice Expressing Cholesterol 7α-Hydroxylase

Studien zur Charakterisierung und zum Stoffwechsel des Lipoprotein-X (LP-X), des abnormen Lipoproteins der Cholestase

Contact Info

Product

Resources

About