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Cannabis effects on lipoproteins.
Lazarte, J, Hegele, RA
Current opinion in lipidology. 2019;(2):140-146
Abstract
PURPOSE OF REVIEW The endocannabinoid system affects several physiological functions. A family of endocannabinoid receptors is susceptible to cannabis constituents. Cannabis is widely used in our society and following its recent legalization in Canada, we focus on how exposure to cannabis and pharmacologic cannabinoid receptor type 1 (CB1) inhibition affect lipoprotein levels. RECENT FINDINGS Several groups have reported that exposure to cannabis does not increase weight despite the marked increase in caloric intake. In observational studies, the effect of smoked cannabis exposure on plasma lipids is variable. Some studies in specific patient populations with longer exposure to cannabis seemed to identify slightly more favorable lipoprotein profiles in the exposed group. Several larger controlled clinical trials using orally administered rimonabant, a CB1 receptor antagonist, have consistently shown relative improvements in weight and plasma levels of triglyceride and high-density lipoprotein cholesterol among patients receiving the treatment. SUMMARY The widely variable findings on the relationship of cannabis in various forms with plasma lipids preclude any definitive conclusions. Cannabis has complex effects on the cardiovascular system and its effects on lipid profile must be considered in this overall context. Further properly controlled research is required to better understand this topic.
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Chylomicron retention disease: genetics, biochemistry, and clinical spectrum.
Levy, E, Poinsot, P, Spahis, S
Current opinion in lipidology. 2019;(2):134-139
Abstract
PURPOSE OF REVIEW Chylomicron retention disease (CRD) is an autosomic recessive disorder, in which intestinal fat malabsorption is the main cause of diverse severe manifestations. The specific molecular defect was identified in 2003 and consists of mutations in the SAR1B or SARA2 gene encoding for intracellular SAR1B GTPase protein. The aim of this review is first to provide an update of the recent biochemical, genetic and clinical findings, and second to discuss novel mechanisms related to hallmark symptoms. RECENT FINDINGS CRD patients present with SAR1B mutations, which disable the formation of coat protein complex II and thus blocks the transport of chylomicron cargo from the endoplasmic reticulum to the Golgi. Consequently, there is a total absence of chylomicron and apolipoprotein B-48 in the blood circulation following a fat meal, accompanied by a deficiency in liposoluble vitamins and essential fatty acids. The recent discovery of Transport and Golgi organization and Transport and Golgi organization-like proteins may explain the intriguing export of large chylomicron, exceeding coat protein complex II size. Hypocholesterolemia could be accounted for by a decrease in HDL cholesterol, likely a reflection of limited production of intestinal HDL in view of reduced ATP-binding cassette family A protein 1 and apolipoprotein A-I protein. In experimental studies, the paralog SAR1A compensates for the lack of the SAR1B GTPase protein. SUMMARY Molecular testing for CRD is recommended to distinguish the disease from other congenital fat malabsorptions, and to early define molecular aberrations, accelerate treatment, and prevent complications.
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Lipid mediators of liver injury in nonalcoholic fatty liver disease.
Liangpunsakul, S, Chalasani, N
American journal of physiology. Gastrointestinal and liver physiology. 2019;(1):G75-G81
Abstract
Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of histopathological phenotypes ranging from simple steatosis to more severe liver disease associated with cell injury, including nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. Only a subset of patients with NAFLD develop NASH from yet incompletely understood mechanisms. Emerging data suggest lipid species other than triglycerides as contributors to the pathogenesis of NASH. In this mini review, we focus on the recent data on the mechanisms of NASH, focusing on these lipid mediators and their potential as therapeutic targets in NASH.
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Beneficial Effects of Pomegranate on Lipid Metabolism in Metabolic Disorders.
Hou, C, Zhang, W, Li, J, Du, L, Lv, O, Zhao, S, Li, J
Molecular nutrition & food research. 2019;(16):e1800773
Abstract
Pomegranate (Punica granatum Linn) is used in the prevention and treatment of metabolic syndrome in recent decades. Imbalances in lipid metabolism are profound features of metabolic disorders. In vivo and in vitro studies have shown that extracts of different pomegranate fractions (peels, flowers, juice, and seeds) regulate lipid metabolism in metabolic-disorder-associated diseases such as atherosclerosis, nonalcoholic fatty liver disease, and type 2 diabetes, helping to alleviate the development of diseases. Amelioration of oxidative stress and the inflammatory response is considered an important reason underlying the regulation of lipid metabolism by pomegranate extracts. Mitochondria, the major cellular site for lipid oxidation, are strongly associated with cellular oxidative and inflammatory status and are likely to be a target for pomegranate extract action. This review summarizes the main findings about the effects of different pomegranate fraction extracts on lipid metabolism in metabolic-disorder-associated diseases and analyses how pomegranate extracts achieve their effects. Furthermore, it also provides an important basis for the research and development of pomegranate-related nutrients or drugs.
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The impact of lipids, lipid oxidation, and inflammation on AMD, and the potential role of miRNAs on lipid metabolism in the RPE.
Jun, S, Datta, S, Wang, L, Pegany, R, Cano, M, Handa, JT
Experimental eye research. 2019;:346-355
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Abstract
The accumulation of lipids within drusen, the epidemiologic link of a high fat diet, and the identification of polymorphisms in genes involved in lipid metabolism that are associated with disease risk, have prompted interest in the role of lipid abnormalities in AMD. Despite intensive investigation, our understanding of how lipid abnormalities contribute to AMD development remains unclear. Lipid metabolism is tightly regulated, and its dysregulation can trigger excess lipid accumulation within the RPE and Bruch's membrane. The high oxidative stress environment of the macula can promote lipid oxidation, impairing their original function as well as producing oxidation-specific epitopes (OSE), which unless neutralized, can induce unwanted inflammation that additionally contributes to AMD progression. Considering the multiple layers of lipid metabolism and inflammation, and the ability to simultaneously target multiple pathways, microRNA (miRNAs) have emerged as important regulators of many age-related diseases including atherosclerosis and Alzheimer's disease. These diseases have similar etiologic characteristics such as lipid-rich deposits, oxidative stress, and inflammation with AMD, which suggests that miRNAs might influence lipid metabolism in AMD. In this review, we discuss the contribution of lipids to AMD pathobiology and introduce how miRNAs might affect lipid metabolism during lesion development. Establishing how miRNAs contribute to lipid accumulation in AMD will help to define the role of lipids in AMD, and open new treatment avenues for this enigmatic disease.
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Crosstalk Between Lipids and Mitochondria in Diabetic Kidney Disease.
Ducasa, GM, Mitrofanova, A, Fornoni, A
Current diabetes reports. 2019;(12):144
Abstract
PURPOSE OF REVIEW The goal of this review is to review the role that renal parenchymal lipid accumulation plays in contributing to diabetic kidney disease (DKD), specifically contributing to the mitochondrial dysfunction observed in glomerular renal cells in the context of DKD development and progression. RECENT FINDINGS Mitochondrial dysfunction has been observed in experimental and clinical DKD. Recently, Ayanga et al. demonstrate that podocyte-specific deletion of a protein involved in mitochondrial dynamics protects from DKD progression. Furthermore, our group has recently shown that ATP-binding cassette A1 (a protein involved in cholesterol and phospholipid efflux) is significantly reduced in clinical and experimental DKD and that genetic or pharmacological induction of ABCA1 is sufficient to protect from DKD. ABCA1 deficiency in podocytes leads to mitochondrial dysfunction observed with alterations of mitochondrial lipids, in particular, cardiolipin (a mitochondrial-specific phospholipid). However, through pharmacological reduction of cardiolipin peroxidation DKD progression is reverted. Lipid metabolism is significantly altered in the diabetic kidney and renders cellular components, such as the podocyte, susceptible to injury leading to worsened DKD progression. Dysfunction of the lipid metabolism pathway can also lead to mitochondrial dysfunction and mitochondrial lipid alteration. Future research aimed at targeting mitochondrial lipids content and function could prove to be beneficial for the treatment of DKD.
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The Regulation of Lipokines by Environmental Factors.
Hernández-Saavedra, D, Stanford, KI
Nutrients. 2019;(10)
Abstract
Adipose tissue is a highly metabolically-active tissue that senses and secretes hormonal and lipid mediators that facilitate adaptations to metabolic tissues. In recent years, the role of lipokines, which are lipid species predominantly secreted from adipose tissue that act as hormonal regulators in many metabolic tissues, has been an important area of research for obesity and diabetes. Previous studies have identified that these secreted lipids, including palmitoleate, 12,13-diHOME, and fatty acid-hydroxy-fatty acids (FAHFA) species, are important regulators of metabolism. Moreover, environmental factors that directly affect the secretion of lipokines such as diet, exercise, and exposure to cold temperatures constitute attractive therapeutic strategies, but the mechanisms that regulate lipokine stimulation have not been thoroughly reviewed. In this study, we will discuss the chemical characteristics of lipokines that position them as attractive targets for chronic disease treatment and prevention and the emerging roles of lipokines as regulators of inter-tissue communication. We will define the target tissues of lipokines, and explore the ability of lipokines to prevent or delay the onset and development of chronic diseases. Comprehensive understanding of the lipokine synthesis and lipokine-driven regulation of metabolic outcomes is instrumental for developing novel preventative and therapeutic strategies that harness adipose tissue-derived lipokines.
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Lipotoxicity plays a key role in the development of both insulin resistance and muscle atrophy in patients with type 2 diabetes.
Meex, RCR, Blaak, EE, van Loon, LJC
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2019;(9):1205-1217
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Abstract
Insulin resistance and muscle mass loss often coincide in individuals with type 2 diabetes. Most patients with type 2 diabetes are overweight, and it is well established that obesity and derangements in lipid metabolism play an important role in the development of insulin resistance in these individuals. Specifically, increased adipose tissue mass and dysfunctional adipose tissue lead to systemic lipid overflow and to low-grade inflammation via altered secretion of adipokines and cytokines. Furthermore, an increased flux of fatty acids from the adipose tissue may contribute to increased fat storage in the liver and in skeletal muscle, resulting in an altered secretion of hepatokines, mitochondrial dysfunction, and impaired insulin signalling in skeletal muscle. Recent studies suggest that obesity and lipid derangements in adipose tissue can also lead to the development of muscle atrophy, which would make insulin resistance and muscle atrophy two sides of the same coin. Unfortunately, the exact relationship between lipid accumulation, type 2 diabetes, and muscle atrophy remains largely unexplored. The aim of this review is to discuss the relationship between type 2 diabetes and muscle loss and to discuss some of the joint pathways through which lipid accumulation in organs may affect peripheral insulin sensitivity and muscle mass.
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Ketogenic Diet: A New Light Shining on Old but Gold Biochemistry.
Longo, R, Peri, C, Cricrì, D, Coppi, L, Caruso, D, Mitro, N, De Fabiani, E, Crestani, M
Nutrients. 2019;(10)
Abstract
Diets low in carbohydrates and proteins and enriched in fat stimulate the hepatic synthesis of ketone bodies (KB). These molecules are used as alternative fuel for energy production in target tissues. The synthesis and utilization of KB are tightly regulated both at transcriptional and hormonal levels. The nuclear receptor peroxisome proliferator activated receptor α (PPARα), currently recognized as one of the master regulators of ketogenesis, integrates nutritional signals to the activation of transcriptional networks regulating fatty acid β-oxidation and ketogenesis. New factors, such as circadian rhythms and paracrine signals, are emerging as important aspects of this metabolic regulation. However, KB are currently considered not only as energy substrates but also as signaling molecules. β-hydroxybutyrate has been identified as class I histone deacetylase inhibitor, thus establishing a connection between products of hepatic lipid metabolism and epigenetics. Ketogenic diets (KD) are currently used to treat different forms of infantile epilepsy, also caused by genetic defects such as Glut1 and Pyruvate Dehydrogenase Deficiency Syndromes. However, several researchers are now focusing on the possibility to use KD in other diseases, such as cancer, neurological and metabolic disorders. Nonetheless, clear-cut evidence of the efficacy of KD in other disorders remains to be provided in order to suggest the adoption of such diets to metabolic-related pathologies.
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Physiology of energy homeostasis: Models, actors, challenges and the glucoadipostatic loop.
Chapelot, D, Charlot, K
Metabolism: clinical and experimental. 2019;:11-25
Abstract
The aim of this review is to discuss the physiology of energy homeostasis (EH), which is a debated concept. Thus, we will see that the set-point theory is highly challenged and that other models integrating an anticipative component, such as energy allostasis, seem more relevant to experimental reports and life preservation. Moreover, the current obesity epidemic suggests that EH is poorly efficient in the modern human dietary environment. Non-homeostatic phenomena linked to hedonism and reward seem to profoundly impair EH. In this review, the apparent failed homeostatic responses to energy challenges such as exercise, cafeteria diet, overfeeding and diet-induced weight loss, as well as their putative determinants, are analyzed to highlight the mechanisms of EH. Then, the hormonal, neuronal, and metabolic factors of energy intake or energy expenditure are briefly presented. Last, this review focuses on the contributions of two of the most pivotal and often overlooked determinants of EH: the availability of endogenous energy and the pattern of energy intake. A glucoadipostatic loop model is finally proposed to link energy stored in adipose tissue to EH through changes in eating behavior via leptin and sympathetic nervous system activity.