scholarly journals Nifedipine Exacerbates Lipogenesis in the Kidney via KIM-1, CD36, and SREBP Upregulation: Implications from an Animal Model for Human Study

2020 ◽  
Vol 21 (12) ◽  
pp. 4359
Author(s):  
Yen-Chung Lin ◽  
Jhih-Cheng Wang ◽  
Mai-Szu Wu ◽  
Yuh-Feng Lin ◽  
Chang-Rong Chen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Renal Fibrosis ◽  
Fatty Acid Synthase ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Kidney Injury ◽  
Low Density ◽  
Ampk Pathway ◽  
Lipid Contents

Dysregulation of fatty acid oxidation and accumulation of fatty acids can cause kidney injury. Nifedipine modulates lipogenesis-related transcriptional factor SREBP-1/2 in proximal tubular cells by inhibiting the Adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK) pathway in vitro. However, the mechanisms by which nifedipine (NF) modulates lipotoxicity in vivo are unclear. Here, we examined the effect of NF in a doxorubicin (DR)-induced kidney injury rat model. Twenty-four Sprague–Dawley rats were divided into control, DR, DR+NF, and high-fat diet (HFD) groups. The DR, DR+NF, and HFD groups showed hypertension and proteinuria. Western blotting and immunohistochemical analysis showed that NF significantly induced TNF-α, CD36, SREBP-1/2, and acetyl-CoA carboxylase expression and renal fibrosis, and reduced fatty acid synthase and AMPK compared to other groups (p < 0.05). Additionally, 18 patients with chronic kidney disease (CKD) who received renal transplants were enrolled to examine their graft fibrosis and lipid contents via transient elastography. Low-density lipoprotein levels in patients with CKD strongly correlated with lipid contents and fibrosis in grafted kidneys (p < 0.05). Thus, NF may initiate lipogenesis through the SREBP-1/2/AMPK pathway and lipid uptake by CD36 upregulation and aggravate renal fibrosis in vivo. Higher low-density lipoprotein levels may correlate with renal fibrosis and lipid accumulation in grafted kidneys of patients with CKD.

scholarly journals The preferential uptake of very-low-density lipoprotein cholesteryl ester by rat liver in vivo

1990 ◽  
Vol 272 (3) ◽  
pp. 735-741 ◽  
Author(s):  
J C Holder ◽  
V A Zammit ◽  
D S Robinson
Keyword(s):  
Fatty Acid ◽  
Cholesteryl Ester ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Apoprotein B ◽  
Preferential Uptake ◽  
Triacylglycerol Fraction

The removal from the blood and the uptake by the liver of injected very-low-density lipoprotein (VLDL) preparations that had been radiolabelled in their apoprotein and cholesteryl ester moieties was studied in lactating rats. Radiolabelled cholesteryl ester was removed from the blood and taken up by the liver more rapidly than sucrose-radiolabelled apoprotein. Near-maximum cholesteryl ester uptake by the liver occurred within 5 min of the injection of the VLDL. At this time, apoprotein B uptake by the liver was only about 25% of the maximum. Maximum uptake of the injected VLDL apoprotein B label was not achieved until at least 15 min after injection, by which time the total uptakes of cholesteryl ester and apoprotein B label were very similar. The results suggest that preferential uptake of the lipoprotein cholesteryl ester by the liver occurred before endocytosis of the entire lipoprotein complex. The fate of the injected VLDL cholesteryl ester after its uptake by the liver was also monitored. Radiolabel associated with the hepatic cholesteryl ester fraction fell steadily from its early maximum level, the rate of fall being faster and more extensive when the fatty acid, rather than the cholesterol, moiety of the ester was labelled. By 30 min after the injection of VLDL containing [3H]cholesteryl ester, over one-third of the injected label was already present as [3H]cholesterol in the liver. When VLDL containing cholesteryl [14C]oleate was injected, a substantial proportion (about 25%) of the injected radiolabelled fatty acid appeared in the hepatic triacylglycerol fraction within 60 min: very little was present in the plasma triacylglycerol fraction at this time.

scholarly journals Lipogenesis and the synthesis and secretion of very low density lipoprotein by avian liver cells in nonproliferating monolayer culture. Hormonal effects.

1977 ◽  
Vol 73 (2) ◽  
pp. 332-353 ◽  
Author(s):  
D M Tarlow ◽  
P A Watkins ◽  
R E Reed ◽  
R S Miller ◽  
E E Zwergel ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
Liver Cells ◽  
Leucine Incorporation ◽  
Very Low Density Lipoprotein ◽  
Low Density

The nonproliferating chicken liver cell culture system described yields cell monolayers with morphological and lipogenic properties characteristic of the physiological-nutritional state of donor animals. Synthesis and secretion of fatty acid, cholesterol, and very low density lipoprotein (VLDL) occur at in vivo rates and respond to hormones and agents which affect these processes in vivo. Cells derived from fed chickens maintain high rates of synthesis of fatty acid and cholesterol for several days if insulin is present in the medium. High rates of fatty acid synthesis are correlated with the appearance of membrane-enclosed triglyceride-rich vesicles in the cytoplasm; deletion of insulin causes a decrease (T1/2 = 22 h) in fatty acid synthetic activity. Addition of glucagon or cyclic AMP (cAMP) causes an immediate cessation of fatty acid synthesis and blocks the appearance of the triglyceride-rich vesicles. Fatty acid synthesis in liver cells prepared from fasted chickens is less than 5% that of cells from fed animals. After 2-3 days in culture with serum-free medium containing insulin +/- triiodothyronine, fatty acid synthesis is restored to normal; glucagon or dibutyryl cAMP blocks this recovery. Liver cells derived from estradiol-treated chickens synthesize and secrete VLDL for at least 48 h in culture. Electron micrographs of these cells reveal more extensive development of the rough endoplasmic reticulum and Golgi complex compared to cells from untreated chickens. Whereas [3H]leucine incorporation into total protein is unaffected by estrogen treatment, [3H]leucine incorporation into cellular and secreted immunoprecipitable VLDL is markedly increased indicating specific activation of VLDL apopeptide synthesis; 8-10% of the labeled protein synthesized and secreted is VLDL. Dodecyl sulfate-acrylamide gel electrophoresis of immunoprecipitated 3H-VLDL reveals three major apopepetides of 300,000, 11,000, and 8,000 daltons corresponding to those of purified chicken VLDL.

Oxidation of Plasma Low-Density Lipoprotein Accelerates Its Accumulation and Degradation in the Arterial Wall In Vivo

Circulation ◽  
1996 ◽  
Vol 94 (7) ◽  
pp. 1698-1704 ◽  
Author(s):  
Klaus Juul ◽  
Lars B. Nielsen ◽  
Klaus Munkholm ◽  
Steen Stender ◽  
Børge G. Nordestgaard
Keyword(s):  
Arterial Wall ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density

scholarly journals Interaction of 4-hydroxynonenal-modified low-density lipoproteins with the fibroblast apolipoprotein B/E receptor

1986 ◽  
Vol 234 (1) ◽  
pp. 245-248 ◽  
Author(s):  
W Jessup ◽  
G Jurgens ◽  
J Lang ◽  
H Esterbauer ◽  
R T Dean
Keyword(s):  
Apolipoprotein B ◽  
Negative Charge ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipid Peroxidation Product ◽  
Modified Low Density Lipoproteins ◽  
Peroxidation Product

The incorporation of the lipid peroxidation product 4-hydroxynonenal into low-density lipoprotein (LDL) increases the negative charge of the particle, and decreases its affinity for the fibroblast LDL receptor. It is suggested that this modification may occur in vivo, and might promote atherogenesis.

scholarly journals Biochemical and cytotoxic characteristics of an in vivo circulating oxidized low density lipoprotein (LDL-).

1994 ◽  
Vol 35 (4) ◽  
pp. 669-677
Author(s):  
H.N. Hodis ◽  
D.M. Kramsch ◽  
P. Avogaro ◽  
G. Bittolo-Bon ◽  
G. Cazzolato ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein
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