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World Journal of Gastroenterology Mar 2016Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is... (Review)
Review
Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is multifactorial, with different lipid profiles observed depending on the immunosuppressive agents administered and the presence of additional risk factors, such as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, the prevention of cardiovascular events has become more important, especially as approximately 64% of liver transplant recipients present with an increased risk of cardiovascular events. Management of dyslipidemia and of other modifiable cardiovascular risk factors, such as hypertension, diabetes and smoking, has therefore become essential in these patients. Treatment of hyperlipidemia after liver transplantation consists of life style modification, modifying the dose or type of immunosuppressive agents and use of lipid lowering agents. At the start of administration of lipid lowering medications, it is important to monitor drug-drug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furthermore, as combinations of various lipid lowering drugs can lead to severe side effects, such as myopathies and rhabdomyolysis, these combinations should therefore be avoided. To our knowledge, there are no current guidelines targeting the management of lipid metabolism disorders in liver transplant recipients. This paper therefore recommends an approach of managing lipid abnormalities occurring after liver transplantation.
Topics: Biomarkers; Drug Interactions; Humans; Hyperlipidemias; Hypolipidemic Agents; Immunosuppressive Agents; Lipids; Liver Transplantation; Risk Factors; Transplant Recipients; Treatment Outcome
PubMed: 27022213
DOI: 10.3748/wjg.v22.i12.3315 -
Lipids in Health and Disease Jan 2022Sitosterolemia is a lipid disorder characterized by the accumulation of phytosterols in plasma and organs, caused by mutations in the ABCG5 and/or ABCG8 genes. The... (Review)
Review
BACKGROUND
Sitosterolemia is a lipid disorder characterized by the accumulation of phytosterols in plasma and organs, caused by mutations in the ABCG5 and/or ABCG8 genes. The disease is frequently misdiagnosed and mistreated as familial hypercholesterolemia (FH). To gain a better understanding of the disease, the current status of diagnosis and treatment of Chinese patients with sitosterolemia was reviewed and summarized.
METHOD
Literature search was performed. The clinical features and molecular characteristics of Chinese patients with sitosterolemia were analysed. Four children with sitosterolemia and the treatment experience were described.
RESULTS
Fifty-five patients with sitosterolemia have been reported in China. These patients were aged from 3 months to 67 years at diagnosis, and the median was 8 years of age. Several complications, such as xanthomas in 47 patients (85%), thrombocytopenia in 17 patients (31%), anemia in 14 patients (25%), and cardiovascular damage in 12 patients (22%), were observed. Thirty-nine patients (71%) exhibited mutations in the ABCG5 gene, 15 patients (27%) showed mutations in ABCG8, and variations in both genes occurred in one patient (2%). A patient with two clinically rare diseases, namely, sitosterolemia and glycogen storage disease type VI (GSD VI)), is reported here for the first time. The four reported patients were treated with low cholesterol and phytosterol-limited diet alone or combined with cholestyramine. Even though decreases were observed for total plasma cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C), and these levels were as low as normal in some patients, the levels of plant sterols remained above the normal range. However, TC, LDL-C and plant sterol levels remained at high levels in patients treated with a control diet control only.
CONCLUSIONS
The analysis reveals that different from Caucasians carrying mainly variations in ABCG8, most Chinese patients have mutations in the ABCG5 gene, and Arg446Ter, Gln251Ter, anArg389His might be hot-spot mutations in Chinese patients. The current survey provides clinical data to enable the development of a standardized protocol for the diagnosis and treatment of sitosterolemia in China.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Adolescent; Adult; Aged; Child; Child, Preschool; China; Female; Humans; Hypercholesterolemia; Infant; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Middle Aged; Mutation; Phytosterols; Young Adult
PubMed: 35042526
DOI: 10.1186/s12944-021-01619-1 -
Deutsches Arzteblatt International Apr 2022
Topics: Humans; Lipid Metabolism; Lipid Metabolism Disorders
PubMed: 35773985
DOI: 10.3238/arztebl.m2022.0057 -
Lipids in Health and Disease Sep 2023Lipid metabolism disorders are considerably involved in the pathology of atherosclerosis; nevertheless, the fundamental mechanism is still largely unclear. This research...
Lipid metabolism disorders are considerably involved in the pathology of atherosclerosis; nevertheless, the fundamental mechanism is still largely unclear. This research sought to examine the function of lipophagy in lipid metabolism disorder-induced atherosclerosis and its fundamental mechanisms. Previously, Sirt6 has been reported to stimulate plaque stability by promoting macrophage autophagy. However, its role in macrophage lipophagy and its relationship with Wnt1 remains to be established. In this study, ApoE: Sirt6 and ApoE: Sirt6Tg mice were used and lipid droplets were analysed via transmission electron microscopy and Bodipy 493/503 staining in vitro. Atherosclerotic plaques in ApoE: Sirt6 mice showed greater necrotic cores and lower stability score. Reconstitution of Sirt6 in atherosclerotic mice improved lipid metabolism disorder and prevented the progression of atherosclerosis. Furthermore, macrophages with Ac-LDL intervention showed more lipid droplets and increased expression of adipophilin and PLIN2. Reconstitution of Sirt6 recruited using SNF2H suppressed Wnt1 expression and improved lipid metabolism disorder by promoting lipophagy. In addition, downregulation of Sirt6 expression in Ac-LDL-treated macrophages inhibited lipid droplet degradation and stimulated foam cell formation. Innovative discoveries in the research revealed that atherosclerosis is caused by lipid metabolism disorders due to downregulated Sirt6 expression. Thus, modulating Sirt6's function in lipid metabolism might be a useful therapeutic approach for treating atherosclerosis.
Topics: Animals; Mice; Lipid Metabolism; beta Catenin; Atherosclerosis; Plaque, Atherosclerotic; Lipid Metabolism Disorders; Macrophages; Apolipoproteins E; Autophagy; Sirtuins
PubMed: 37736721
DOI: 10.1186/s12944-023-01891-3 -
Biochimica Et Biophysica Acta Apr 2015Metabolic myopathies are disorders of utilization of carbohydrates or fat in muscles. The acute nature of energy failure is manifested either by a metabolic crisis with... (Review)
Review
Metabolic myopathies are disorders of utilization of carbohydrates or fat in muscles. The acute nature of energy failure is manifested either by a metabolic crisis with weakness, sometimes associated with respiratory failure, or by myoglobinuria. A typical disorder where permanent weakness occurs is glycogenosis type II (GSDII or Pompe disease) both in infantile and late-onset forms, where respiratory insufficiency is manifested by a large number of cases. In GSDII the pathogenetic mechanism is still poorly understood, and has to be attributed more to structural muscle alterations, possibly in correlation to macro-autophagy, rather than to energetic failure. This review is focused on recent advances about GSDII and its treatment, and the most recent notions about the management and treatment of other metabolic myopathies will be briefly reviewed, including glycogenosis type V (McArdle disease), glycogenosis type III (debrancher enzyme deficiency or Cori disease), CPT-II deficiency, and ETF-dehydrogenase deficiency (also known as riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency or RR-MADD). The discovery of the genetic defect in ETF dehydrogenase confirms the etiology of this syndrome. Other metabolic myopathies with massive lipid storage and weakness are carnitine deficiency, neutral lipid storage-myopathy (NLSD-M), besides RR-MADD. Enzyme replacement therapy is presented with critical consideration and for each of the lipid storage disorders, representative cases and their response to therapy is included. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
Topics: Animals; Electron-Transferring Flavoproteins; Enzyme Replacement Therapy; Glycogen Storage Disease; Humans; Iron-Sulfur Proteins; Lipid Metabolism, Inborn Errors; Muscular Diseases; Oxidoreductases Acting on CH-NH Group Donors
PubMed: 24997454
DOI: 10.1016/j.bbadis.2014.06.031 -
International Journal of Molecular... Nov 2022Krabbe disease (KD) is a rare autosomal recessive disorder caused by mutations in the galactocerebrosidase gene (). Defective GALC causes aberrant metabolism of...
Krabbe disease (KD) is a rare autosomal recessive disorder caused by mutations in the galactocerebrosidase gene (). Defective GALC causes aberrant metabolism of galactolipids present almost exclusively in myelin, with consequent demyelinization and neurodegeneration of the central and peripheral nervous system (NS). KD shares some similar features with other neuropathies and heterozygous carriers of mutations are emerging with an increased risk in developing NS disorders. In this work, we set out to identify possible variations in the proteomic profile of KD-carrier brain to identify altered pathways that may imbalance its homeostasis and that may be associated with neurological disorders. The differential analysis performed on whole brains from 33-day-old twitcher (), heterozygous ( and wild-type mice highlighted the dysregulation of several multifunctional factors in both heterozygous and twitcher mice. Notably, the KD-carrier mouse, despite its normal phenotype, presents the deregulation of vimentin, receptor of activated protein C kinase 1 (RACK1), myelin basic protein (MBP), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP), transitional endoplasmic reticulum ATPase (VCP), and N-myc downstream regulated gene 1 protein (NDRG1) as well as changes in the ubiquitinated-protein pattern. Our findings suggest the carrier may be affected by dysfunctions classically associated with neurodegeneration: (i) alteration of (mechano) signaling and intracellular trafficking, (ii) a generalized affection of proteostasis and lipid metabolism, with possible defects in myelin composition and turnover, and (iii) mitochondrion and energy supply dysfunctions.
Topics: Animals; Mice; Leukodystrophy, Globoid Cell; Proteomics; Disease Models, Animal; Galactosylceramidase; Neurodegenerative Diseases
PubMed: 36362324
DOI: 10.3390/ijms232113537 -
European Journal of Clinical... Nov 2022Patients with severe hypertriglyceridaemia (sHTG) are often refractory to lipid-lowering therapy. Apolipoprotein (Apo) CIII inhibition could be promising to treat... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with severe hypertriglyceridaemia (sHTG) are often refractory to lipid-lowering therapy. Apolipoprotein (Apo) CIII inhibition could be promising to treat subjects with sHTG. The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat sHTG. We performed a systematic review and meta-analysis of RCTs on the efficacy and safety of volanesorsen as compared to placebo treatment in patients with severe HTG.
METHODS
Studies were systematically searched in the PubMed, Web of Science and Scopus databases according to PRISMA guidelines. The last search was performed on 7 February 2022.
RESULTS
Four studies showed significant reduction in TG after 3 months of treatment with volanesorsen as compared with placebo (MD: -73.9%; 95%CI: -93.5%, -54.2; p < .001 I = 89.05%; p < .001); VLDL-C level (MD: -71.0%; 95%CI: -76.6%, -65.4%; p < .001 I = 94.1%; p < .001); Apo-B48 level (MD: -69.03%; 95%CI: -98.59.4%, -39.47%; p < .001, I = 93.51%; p < .001) and Apo-CIII level (MD: -80.0%; 95%CI: -97.5%, -62.5; p < .001 I = 94.1%; p < .001) with an increase in HDL-C level (MD: +45.92%, 95%CI: +37.24%, +54.60%; p < .001 I = 94.34%; p < .001) and in LDL-C level (MD: +68.6%, 95%CI: +7.0%, +130.1%; p < .001 I = 96.18%; p < .001) without a significant elevation of Apo-B100 level (MD: +4.58%, 95%CI: -5.64%, +14.79%; p = .380 I = 95.09%; p < .001) in 139 volanesorsen patients as compared to 100 placebo-treated controls. Most of adverse events were mild and related to local injection site reactions.
CONCLUSIONS
In patients with severe HTG, volanesorsen is associated with a significant reduction in TG, VLDL-C, Apo-B48 and non-HDL-C and increment of HDL-C as compared to placebo. Documented efficacy is accompanied by an acceptable safety profile.
Topics: Apolipoprotein B-48; Apolipoprotein C-III; Cholesterol, LDL; Humans; Hyperlipidemias; Hypertriglyceridemia; Oligonucleotides; Oligonucleotides, Antisense; RNA, Messenger; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 35851450
DOI: 10.1111/eci.13841 -
Current Opinion in Lipidology Jun 2019The purpose of the review is to discuss recent advances in microRNA (miRNA) regulation of lipid metabolism and highlight the importance of miRNA-mediated gene regulation... (Review)
Review
PURPOSE OF REVIEW
The purpose of the review is to discuss recent advances in microRNA (miRNA) regulation of lipid metabolism and highlight the importance of miRNA-mediated gene regulation in dyslipidemia and fatty liver disease. This article reviews examples of miRNAs that bridge disparate metabolic pathways in the liver. For example, we highlight miRNAs that are regulated by the sterol-sensing pathway in the liver that in turn regulate cellular or systemic cholesterol, fatty acid, and glucose levels.
RECENT FINDINGS
The most widely studied of these miRNAs are miR-33a/b; however, we recently reported that miRNAs in the miR-183/96/182 cluster are also likely regulated by hepatic cholesterol content and mediate the observed glucose-lowering effects of the bile acid sequestrant colesevelam through the sterol-sensing pathway. In addition, several other hepatic and adipose miRNAs have been recently demonstrated to be key regulators of cellular lipid synthesis, storage, and catabolism, as well as systemic lipid metabolism. Moreover, many of these miRNAs are altered in fatty liver disease and dyslipidemia.
SUMMARY
miRNAs are not just fine-tuners of lipid metabolism, but critical regulatory factors in lipid homeostasis and health. Loss of these miRNA regulatory modules very likely contributes to the underlying metabolic defects observed in lipid disorders.
Topics: Animals; Dyslipidemias; Humans; Lipid Metabolism; MicroRNAs
PubMed: 30985366
DOI: 10.1097/MOL.0000000000000603 -
Endokrynologia Polska 2022Nearly 30% of patients with lipid profile abnormalities suffer from secondary dyslipidaemias. Endocrine disorders are one of the most important causes of dyslipidaemia.... (Review)
Review
Nearly 30% of patients with lipid profile abnormalities suffer from secondary dyslipidaemias. Endocrine disorders are one of the most important causes of dyslipidaemia. Dyslipidaemia can be observed in the pathologies of a variety of endocrine glands, including the thyroid, the pituitary, the adrenals, and the gonads. The most common endocrinopathy causing dyslipidaemia is hypothyroidism. In this paper, we review the lipid profile alterations observed in endocrinopathies. We describe changes in classic lipid profile parameters, including total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. However, we also focus on the influence of endocrine disorders on relatively new cardiovascular markers such as apolipoprotein B, apolipoprotein A1, and lipoprotein(a). While almost all endocrinopathies cause detrimental changes to the lipid profile, hyperthyroidism seems to be a disorder in which lowering of such parameters as total cholesterol, low-density cholesterol, and triglycerides can be observed. Comprehensive screening for endocrine disorders should always be included in the differential diagnostic process of secondary causes of dyslipidaemia. Early detection and treatment of endocrinopathy have a considerable impact on a patient's health. Proper treatment of those disorders plays a crucial role in modifying the cardiovascular risk and improving the lipid profile of those patients. Even though lipid-lowering therapy is usually still needed, in some cases restoration of hormonal balance might be sufficient to normalize the lipid profile abnormalities.
Topics: Humans; Endocrine System Diseases; Hypothyroidism; Cholesterol, LDL; Triglycerides; Dyslipidemias
PubMed: 35971925
DOI: 10.5603/EP.a2022.0059 -
Revista de Investigacion Clinica;... 2018The purpose of this manuscript is to highlight the peculiarities of the Mexican population regarding the clinical expression, genetics, and treatment of lipid disorders.... (Review)
Review
The purpose of this manuscript is to highlight the peculiarities of the Mexican population regarding the clinical expression, genetics, and treatment of lipid disorders. Furthermore, it is a call for action to address the existing gaps in care and research of dyslipidemias. The Mexican Mestizos are highly susceptible to metabolic disorders (i.e., low high-density lipoprotein cholesterol concentrations, hypertriglyceridemia, abdominal obesity, and type 2 diabetes); these conditions are associated with ethnic-specific genetic variants. On the other hand, despite the high prevalence of dyslipidemia in Mexican adults, there is a lack of awareness of these conditions. The public is not informed about the need for screening and the potential benefit of the lipid-lowering treatments. Underdiagnosis and undertreatment are two of the main challenges to be solved. Dyslipidemias are not among the priorities of the health systems for the prevention of cardiovascular disease; access to laboratory resources and medications is insufficient in primary care units despite the proven cost-benefit of the treatment of lipid disorders. Evidence-based public policies are needed to change the practice and allocation of assets to be capable of preventing cardiovascular diseases. Treatment of dyslipidemia should have a prominent role in any effort to decrease the number of preventable deaths caused by non-communicable diseases.
Topics: Adult; Cardiovascular Diseases; Dyslipidemias; Genetic Predisposition to Disease; Humans; Metabolic Diseases; Mexico; Prevalence; Public Policy; Risk Factors
PubMed: 30307444
DOI: 10.24875/RIC.18002573