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Nutrients Jan 2020Menopause is clinically diagnosed as a condition when a woman has not menstruated for one year. During the menopausal transition period, there is an emergence of various... (Review)
Review
Menopause is clinically diagnosed as a condition when a woman has not menstruated for one year. During the menopausal transition period, there is an emergence of various lipid metabolic disorders due to hormonal changes, such as decreased levels of estrogens and increased levels of circulating androgens; these may lead to the development of metabolic syndromes including cardiovascular diseases and type 2 diabetes. Dysregulation of lipid metabolism affects the body fat mass, fat-free mass, fatty acid metabolism, and various aspects of energy metabolism, such as basal metabolic ratio, adiposity, and obesity. Moreover, menopause is also associated with alterations in the levels of various lipids circulating in the blood, such as lipoproteins, apolipoproteins, low-density lipoproteins (LDLs), high-density lipoproteins (HDL) and triacylglycerol (TG). Alterations in lipid metabolism and excessive adipose tissue play a key role in the synthesis of excess fatty acids, adipocytokines, proinflammatory cytokines, and reactive oxygen species, which cause lipid peroxidation and result in the development of insulin resistance, abdominal adiposity, and dyslipidemia. This review discusses dietary recommendations and beneficial compounds, such as vitamin D, omega-3 fatty acids, antioxidants, phytochemicals-and their food sources-to aid the management of abnormal lipid metabolism in postmenopausal women.
Topics: Adult; Aged; Estrogens; Fatty Acids, Omega-3; Female; Humans; Lipid Metabolism; Lipid Metabolism Disorders; Menopause; Middle Aged; Obesity; Phytochemicals; Postmenopause; Probiotics; Vitamin D
PubMed: 31941004
DOI: 10.3390/nu12010202 -
Trends in Molecular Medicine Jun 2023Lysosomal acid lipase (LAL) is the sole enzyme known to degrade neutral lipids in the lysosome. Mutations in the LAL-encoding LIPA gene lead to rare lysosomal lipid... (Review)
Review
Lysosomal acid lipase (LAL) is the sole enzyme known to degrade neutral lipids in the lysosome. Mutations in the LAL-encoding LIPA gene lead to rare lysosomal lipid storage disorders with complete or partial absence of LAL activity. This review discusses the consequences of defective LAL-mediated lipid hydrolysis on cellular lipid homeostasis, epidemiology, and clinical presentation. Early detection of LAL deficiency (LAL-D) is essential for disease management and survival. LAL-D must be considered in patients with dyslipidemia and elevated aminotransferase concentrations of unknown etiology. Enzyme replacement therapy, sometimes in combination with hematopoietic stem cell transplantation (HSCT), is currently the only therapy for LAL-D. New technologies based on mRNA and viral vector gene transfer are recent efforts to provide other effective therapeutic strategies.
Topics: Humans; Wolman Disease; Sterol Esterase; Hematopoietic Stem Cell Transplantation; Lipids
PubMed: 37028992
DOI: 10.1016/j.molmed.2023.03.001 -
Nutrients Dec 2021Aging women experience hormonal changes, such as decreased estrogen and increased circulating androgen, due to natural or surgical menopause. These hormonal changes make... (Review)
Review
Aging women experience hormonal changes, such as decreased estrogen and increased circulating androgen, due to natural or surgical menopause. These hormonal changes make postmenopausal women vulnerable to body composition changes, muscle loss, and abdominal obesity; with a sedentary lifestyle, these changes affect overall energy expenditure and basal metabolic rate. In addition, fat redistribution due to hormonal changes leads to changes in body shape. In particular, increased bone marrow-derived adipocytes due to estrogen loss contribute to increased visceral fat in postmenopausal women. Enhanced visceral fat lipolysis by adipose tissue lipoprotein lipase triggers the production of excessive free fatty acids, causing insulin resistance and metabolic diseases. Because genes involved in β-oxidation are downregulated by estradiol loss, excess free fatty acids produced by lipolysis of visceral fat cannot be used appropriately as an energy source through β-oxidation. Moreover, aged women show increased adipogenesis due to upregulated expression of genes related to fat accumulation. As a result, the catabolism of ATP production associated with β-oxidation decreases, and metabolism associated with lipid synthesis increases. This review describes the changes in energy metabolism and lipid metabolic abnormalities that are the background of weight gain in postmenopausal women.
Topics: Adipogenesis; Aged; Body Composition; Energy Metabolism; Estradiol; Estrogens; Fatty Acids, Nonesterified; Female; Humans; Insulin Resistance; Intra-Abdominal Fat; Lipid Metabolism; Lipid Metabolism Disorders; Lipolysis; Lipoprotein Lipase; Middle Aged; Muscle, Skeletal; Obesity, Abdominal; Oxidation-Reduction; Postmenopause
PubMed: 34960109
DOI: 10.3390/nu13124556 -
Circulation Research Feb 2021Lipid uptake and metabolism are central to the function of organs such as heart, skeletal muscle, and adipose tissue. Although most heart energy derives from fatty acids... (Review)
Review
Lipid uptake and metabolism are central to the function of organs such as heart, skeletal muscle, and adipose tissue. Although most heart energy derives from fatty acids (FAs), excess lipid accumulation can cause cardiomyopathy. Similarly, high delivery of cholesterol can initiate coronary artery atherosclerosis. Hearts and arteries-unlike liver and adrenals-have nonfenestrated capillaries and lipid accumulation in both health and disease requires lipid movement from the circulation across the endothelial barrier. This review summarizes recent in vitro and in vivo findings on the importance of endothelial cell receptors and uptake pathways in regulating FAs and cholesterol uptake in normal physiology and cardiovascular disease. We highlight clinical and experimental data on the roles of ECs in lipid supply to tissues, heart, and arterial wall in particular, and how this affects organ metabolism and function. Models of FA uptake into ECs suggest that receptor-mediated uptake predominates at low FA concentrations, such as during fasting, whereas FA uptake during lipolysis of chylomicrons may involve paracellular movement. Similarly, in the setting of an intact arterial endothelial layer, recent and historic data support a role for receptor-mediated processes in the movement of lipoproteins into the subarterial space. We conclude with thoughts on the need to better understand endothelial lipid transfer for fuller comprehension of the pathophysiology of hyperlipidemia, and lipotoxic diseases such as some forms of cardiomyopathy and atherosclerosis.
Topics: Animals; CD36 Antigens; Cholesterol; Chylomicrons; Endothelial Cells; Fatty Acid Transport Proteins; Fatty Acids; Humans; Lipid Metabolism Disorders; Lipolysis; Particle Size; Transcytosis
PubMed: 33539224
DOI: 10.1161/CIRCRESAHA.120.318003 -
Atherosclerosis Jul 2021Apolipoprotein E (apoE) is a major apolipoprotein involved in lipoprotein metabolism. It is a polymorphic protein and different isoforms are associated with variations... (Review)
Review
Apolipoprotein E (apoE) is a major apolipoprotein involved in lipoprotein metabolism. It is a polymorphic protein and different isoforms are associated with variations in lipid and lipoprotein levels and thus cardiovascular risk. The isoform apoE4 is associated with an increase in LDL-cholesterol levels and thus a higher cardiovascular risk compared to apoE3. Whereas, apoE2 is associated with a mild decrease in LDL-cholesterol levels. In the presence of other risk factors, apoE2 homozygotes could develop type III hyperlipoproteinemia (familial dysbetalipoproteinemia or FD), an atherogenic disorder characterized by an accumulation of remnants of triglyceride-rich lipoproteins. Several rare APOE gene variants were reported in different types of dyslipidemias including FD, familial combined hyperlipidemia (FCH), lipoprotein glomerulopathy and bona fide autosomal dominant hypercholesterolemia (ADH). ADH is characterized by elevated LDL-cholesterol levels leading to coronary heart disease, and due to molecular alterations in three main genes: LDLR, APOB and PCSK9. The identification of the APOE-p.Leu167del variant as the causative molecular element in two different ADH families, paved the way to considering APOE as a candidate gene for ADH. Due to non mendelian interacting factors, common genetic and environmental factors and perhaps epigenetics, clinical presentation of lipid disorders associated with APOE variants often strongly overlap. More studies are needed to determine the spectrum of APOE implication in each of the diseases, notably ADH, in order to improve clinical and genetic diagnosis, prognosis and patient management. The purpose of this review is to comment on these APOE variants and on the molecular and clinical overlaps between dyslipidemias.
Topics: Apolipoproteins E; Dyslipidemias; Humans; Hyperlipoproteinemia Type II; Proprotein Convertase 9; Receptors, LDL
PubMed: 34058468
DOI: 10.1016/j.atherosclerosis.2021.05.007 -
Journal of Clinical Lipidology 2022The Abetalipoproteinemia and Related Disorders Foundation was established in 2019 to provide guidance and support for the life-long management of inherited... (Review)
Review
The Abetalipoproteinemia and Related Disorders Foundation was established in 2019 to provide guidance and support for the life-long management of inherited hypocholesterolemia disorders. Our mission is "to improve the lives of individuals and families affected by abetalipoproteinemia and related disorders". This review explains the molecular mechanisms behind the monogenic hypobetalipoproteinemia disorders and details their specific pathophysiology, clinical presentation and management throughout the lifespan. In this review, we focus on abetalipoproteinemia, homozygous hypobetalipoproteinemia and chylomicron retention disease; rare genetic conditions that manifest early in life and cause severe complications without appropriate treatment. Absent to low plasma lipid levels, in particular cholesterol and triglyceride, along with malabsorption of fat and fat-soluble vitamins are characteristic features of these diseases. We summarize the genetic basis of these disorders, provide guidance in their diagnosis and suggest treatment regimens including high dose fat-soluble vitamins as therapeutics. A section on preconception counseling and other special considerations pertaining to pregnancy is included. This information may be useful for patients, caregivers, physicians and insurance agencies involved in the management and support of affected individuals.
Topics: Humans; Abetalipoproteinemia; Hypobetalipoproteinemias; Lipid Metabolism Disorders; Homozygote; Vitamins
PubMed: 36243606
DOI: 10.1016/j.jacl.2022.08.009 -
Lipids in Health and Disease Feb 2020Hyperlipidemia is a common metabolic disorder and one of risk factors for cardiovascular disease. Clinical studies have shown that hyperlipidemia increases the risk of... (Review)
Review
Hyperlipidemia is a common metabolic disorder and one of risk factors for cardiovascular disease. Clinical studies have shown that hyperlipidemia increases the risk of non-ischemic heart failure, while decreasing serum lipids can reverse heart dysfunction. Apart from indirectly affecting the function of the heart by promoting the development of atherosclerosis, hyperlipidemia also affects the systolic function and cardiac electrophysiological response of the heart directly, which may be related to gradual accumulation of cardiac lipids and consequent systemic oxidative stress, proinflammatory state and mitochondrial dysfunction. However, the mechanism underlying direct effects of hyperlipidemia on the heart are not fully understood. In this review, we provide an updated summary of recent experimental and clinical studies that focus on elucidating the mechanisms of the action of hyperlipidemia on cardiac function, the relationship between heart failure and serum lipids, and protective effects of lipid-lowering drugs on the heart. The exciting progress in this field supports the prospect of guiding early protection of the heart to benefit the patients with chronic hyperlipidemia and familial hyperlipidemia.
Topics: Heart Failure; Humans; Hyperlipidemias; Hypolipidemic Agents; Myocardium; Oxidative Stress
PubMed: 32035485
DOI: 10.1186/s12944-019-1171-8 -
Endocrinology, Diabetes & Metabolism Jan 2023Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) is the most common inherited metabolic disorder of β-oxidation. Patients with MCADD present with hypoketotic... (Review)
Review
INTRODUCTION
Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) is the most common inherited metabolic disorder of β-oxidation. Patients with MCADD present with hypoketotic hypoglycemia, which may quickly progress to lethargy, coma, and death. Prognosis for MCADD patients is highly promising once a diagnosis has been established, though management strategies may vary depending on the severity of illness and the presence of comorbidities.
METHODS AND RESULTS
Given the rapid developments in the world of gene therapy and implementation of newborn screening for inherited metabolic disorders, the provision of concise and contemporary knowledge of MCADD is essential for clinicians to effectively manage patients. Thus, this review aims to consolidate current information for physicians on the pathogenesis, diagnostic tools, and treatment options for MCADD patients.
CONCLUSION
MCADD is a commonly inherited metabolic disease with serious implications for health outcomes, particularly in children, that may be successfully managed with proper intervention.
Topics: Infant, Newborn; Child; Humans; Acyl-CoA Dehydrogenase; Lipid Metabolism, Inborn Errors; Neonatal Screening; Hypoglycemia
PubMed: 36300606
DOI: 10.1002/edm2.385 -
FEBS Letters Oct 2006Drug-induced phospholipidosis is characterized by intracellular accumulation of phospholipids with lamellar bodies, most likely from an impaired phospholipid metabolism... (Review)
Review
Drug-induced phospholipidosis is characterized by intracellular accumulation of phospholipids with lamellar bodies, most likely from an impaired phospholipid metabolism of the lysosome. Organs affected by phospholipidosis exhibit inflammatory reactions and histopathological changes. Despite significant advances in the understanding of drug-altered lipid metabolism, the relationship between impaired phospholipid metabolism and drug-induced toxicity remains enigmatic. Here we review molecular features of inheritable lysosomal storage disorders as a molecular mimicry of drug-induced phospholipidosis for an improved understanding of adverse drug reaction.
Topics: Animals; Humans; Lipidoses; Lysosomes; Phospholipids
PubMed: 16979167
DOI: 10.1016/j.febslet.2006.08.061 -
Theranostics 2020The functions of fibrinogen-like protein 2 (fgl2) have been studied in many inflammatory and neoplastic diseases, but the role of fgl2 in nonalcoholic fatty liver...
Fibrinogen-like protein 2 aggravates nonalcoholic steatohepatitis via interaction with TLR4, eliciting inflammation in macrophages and inducing hepatic lipid metabolism disorder.
The functions of fibrinogen-like protein 2 (fgl2) have been studied in many inflammatory and neoplastic diseases, but the role of fgl2 in nonalcoholic fatty liver disease has not yet been elucidated. In this study, we sought to investigate the role of fgl2 in the pathogenesis of nonalcoholic steatohepatitis (NASH). Hepatic fgl2 expression was tested in patients with nonalcoholic fatty liver (NAFL) or NASH and controls. Wild-type and fgl2-/- C57BL/6 mice were subjected to a methionine/choline-deficient (MCD) diet or a high-fat diet (HFD) to establish NASH models. Bone marrow-derived macrophages (BMDMs) stimulated with LPS or free fatty acids were used for the study. In both humans and mice with NASH, macrophage accumulation was concomitant with significantly increased fgl2 expression in the liver. Fgl2 deficiency attenuated liver steatosis and inflammation in diet-induced murine models of NASH. In both liver tissues and BMDMs from NASH mice, fgl2 deficiency resulted in reduced levels of proinflammatory cytokines and reactive oxygen species (ROS) compared with levels in wild-type controls. Activation of NF-κB, p38-MAPK and NLRP3 inflammasomes was also suppressed upon fgl2 disruption. Moreover, lipogenic genes (Fasn and SREBP-2) were downregulated while lipolytic genes (PPAR and CPT1A) were upregulated in the livers of fgl2-/- NASH mice. Primary hepatocytes incubated with the medium collected from fgl2-/- BMDMs showed less fat deposition than those incubated with WT BMDMs. Furthermore, we discovered that fgl2 combined with TLR4 mediates the activation of the Myd88-dependent signaling pathway, which may contribute to inflammation and lipid metabolism disorders. These data suggest that fgl2 aggravates the progression of NASH through activation of NF-κB, p38-MAPK and NLRP3 inflammasomes in macrophages, which consequently induces overproduction of proinflammatory cytokines and lipid metabolism disorders. An interaction of fgl2 and TLR4 may in part contribute to the activation of inflammatory signaling pathways in macrophages.
Topics: Animals; Cytokines; Diet, High-Fat; Fibrinogen; Hepatocytes; Humans; Inflammation; Lipid Metabolism; Lipid Metabolism Disorders; Lipogenesis; Liver; Liver Cirrhosis; Macrophages; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Non-alcoholic Fatty Liver Disease; Reactive Oxygen Species; Signal Transduction; Toll-Like Receptor 4
PubMed: 32863955
DOI: 10.7150/thno.44297