Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans

Dietschy, John M.; Turley, Stephen D.; Spady, David K.

doi:10.1016/s0022-2275(20)35728-x

Cited by 745 publications

(99 citation statements)

References 102 publications

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“…Our results showed that berberine treatment significantly lowered the TG and FFA levels in western-type diet-induced ApoE -/mice, indicating the lipid-lowering effect of berberine. In addition, the liver is a crucial organ of lipid metabolism and is responsible for maintaining the homeostasis of cholesterol and LDL [26]. We observed hepatic lipid accumulation.…”

Section: Discussionmentioning

confidence: 62%

Improvement of Endothelial Dysfunction of Berberine in Atherosclerotic Mice and Mechanism Exploring through TMT-Based Proteomics

Tan

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Atherosclerosis is a multifactorial vascular disease triggered by disordered lipid metabolism, characterized by chronic inflammatory injury, and initiated by endothelial dysfunction. Berberine is the main active alkaloid of the herbal medicine Coptidis Rhizoma (Huanglian). Notably, berberine has been shown to have beneficial effects against atherosclerosis. However, the mechanisms of berberine in preventing atherosclerosis are still unclear. This study is aimed at investigating the effects and mechanisms of berberine in protecting the aorta and ameliorating atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. Here, we demonstrated that berberine reduced serum lipid levels, antagonized hepatic lipid accumulation, improved intima-media thickening, and alleviated atherosclerotic lesions in ApoE-/- mice fed a western-type diet for 12 weeks. Meanwhile, berberine reduced aortic reactive oxygen species (ROS) generation and reduced the serum levels of malondialdehyde (MDA), oxidized low-density lipoprotein (ox-LDL), and interleukin-6 (IL-6). In aortic ring assay, berberine restored aortic endothelium-dependent vasodilatation in vivo and in vitro. Furthermore, 4,956 proteins were identified by proteomic analysis, and 199 differentially expressed proteins regulated by berberine were found to be involved in many biological pathways, such as mitochondrial dysfunction, fatty acid β-oxidation I, and FXR/RXR activation. Summarily, these data suggested that berberine ameliorates endothelial dysfunction and protects against atherosclerosis, and thus may be a promising therapeutic candidate for atherosclerosis.

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Section: Discussionmentioning

confidence: 62%

Improvement of Endothelial Dysfunction of Berberine in Atherosclerotic Mice and Mechanism Exploring through TMT-Based Proteomics

Tan

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Different metabolic processes in different organs may be overlapping, leaving an interpretation extremely difficult (Ametaj, 2015). Also, the implication and functional relevance of an increase or decrease of many metabolites are often not fully elucidated (Goldansaz et al, 2017) and comparison between species has to been seen critically (Dietschy et al, 1993;Lin, 1998;Andes and Craig, 2002;Ball et al, 2007). These 3 aspects are of special relevance in dairy cow research.…”

Section: Effects Of Butaphosphan and Cyanocobalaminmentioning

confidence: 99%

Aspects of transition cow metabolomics—Part I: Effects of a metaphylactic butaphosphan and cyanocobalamin treatment on the metabolome in liver, blood, and urine in cows with different liver metabotypes

Schären

Snedec

Riefke

et al. 2021

Journal of Dairy Science

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Dairy cows in modern production systems are at risk to develop metabolic disorders during the transition period. Reasons for individual differences in susceptibility, as well as the underlying pathomechanisms, are still only partially understood. The development of metaphylactic treatment protocols is needed. In this context, an on-farm prospective 3-fold blinded randomized study involving 80 German Holstein cows was performed throughout 1 yr. The trial involved a thorough recording of the production and clinical traits, clinical chemistry, and liver biopsies and blood and urine sampling at d 14 (mean: 12 d, range: 1-26 d) antepartum (AP), and d 7 (7, 4-13) and 28 (28, 23-34) postpartum (PP) for metabolomics analyses. Two groups received a treatment with butaphosphan and cyanocobalamin (BCC) at either the dosage recommended by the manufacturer or the double dosage (5 or 10 mL/100 kg of body weight 10% butaphosphan and 0.005% cyanocobalamin (Catosal, Bayer Animal Health), n = 20 in each group, parity: 4.2 ± 2.0 and 3.4 ± 1.3, respectively (mean ± SD)] and one group a placebo treatment (NaCl 0.9%, n = 40, parity: 4.0 ± 1.9). The animals were treated at 6 time points (7, 6, and 5 d AP, and 1, 2, and 3 d PP) via intravenous injection. Mass spectroscopy-based targeted metabolomics analysis of blood plasma and liver samples were performed using the AbsoluteIDQ p180 kit (Biocrates Life Sciences), whereas the urine samples were analyzed by nuclear magnetic resonance

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“…Mounting evidence suggests the resultant abnormalities are linked to dietary and genetic factors. LDL-c is cholesterol that is available for delivery and cellular uptake; the circulating concentration is linked directly to dietary cholesterol consumption and associated with both cardiovascular disease and cholesterol gallstone formation [11,34]. HDL-c, excess cholesterol transported from cells to the liver for excretion in a process called reverse cholesterol transport, is considered the "healthier" cholesterol due to protective properties against atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

“…Demographic, environmental and genetic factors may all contribute to altered cholesterol homeostasis [10], presenting complex molecular events that favour gallstone formation. Cholesterol homeostasis is maintained by various endogenous responses involving cholesterol synthesis, transport and excretion [11,12].…”

Section: Introductionmentioning

confidence: 99%

Hepatic expression of cholesterol regulating genes favour increased circulating low-density lipoprotein in HIV infected patients with gallstone disease: a preliminary study

et al. 2021

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Background HIV endemic populations are displaying higher incidence of metabolic disorders. HIV and the standard treatment are both associated with altered lipid and cholesterol metabolism, however gallstone disease (a cholesterol related disorder) in Sub-Saharan African populations is rarely investigated. Methods This study sought to evaluate hepatic expression of key genes in cholesterol metabolism (LDLr, HMGCR, ABCA1) and transcriptional regulators of these genes (microRNA-148a, SREBP2) in HIV positive patients on antiretroviral therapy presenting with gallstones. Liver biopsies from HIV positive patients (cases: n = 5) and HIV negative patients (controls: n = 5) were analysed for miR-148a and mRNA expression using quantitative PCR. Results Circulating total cholesterol was elevated in the HIV positive group with significantly elevated LDL-c levels(3.16 ± 0.64 mmol/L) relative to uninfected controls (2.10 ± 0.74 mmol/L; p = 0.04). A scavenging receptor for LDL-c, LDLr was significantly decreased (0.18-fold) in this group, possibly contributing to higher LDL-c levels. Transcriptional regulator of LDLr, SREBP2 was also significantly lower (0.13-fold) in HIV positive patients. Regulatory microRNA, miR-148a-3p, was reduced in HIV positive patients (0.39-fold) with a concomitant increase in target ABCA1 (1.5-fold), which regulates cholesterol efflux. Conclusions Collectively these results show that HIV patients on antiretroviral therapy display altered hepatic regulation of cholesterol metabolizing genes, reducing cholesterol scavenging, and increasing cholesterol efflux.

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Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans

Cited by 745 publications

References 102 publications

Improvement of Endothelial Dysfunction of Berberine in Atherosclerotic Mice and Mechanism Exploring through TMT-Based Proteomics

Improvement of Endothelial Dysfunction of Berberine in Atherosclerotic Mice and Mechanism Exploring through TMT-Based Proteomics

Aspects of transition cow metabolomics—Part I: Effects of a metaphylactic butaphosphan and cyanocobalamin treatment on the metabolome in liver, blood, and urine in cows with different liver metabotypes

Hepatic expression of cholesterol regulating genes favour increased circulating low-density lipoprotein in HIV infected patients with gallstone disease: a preliminary study

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