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1.
New insights into purine metabolism in metabolic diseases: role of xanthine oxidoreductase activity.
Furuhashi, M
American journal of physiology. Endocrinology and metabolism. 2020;(5):E827-E834
Abstract
Xanthine oxidoreductase (XOR) consists of two different forms, xanthine dehydrogenase and xanthine oxidase (XO), and is a rate-limiting enzyme of uric acid production from hypoxanthine and xanthine. Uric acid is the end product of purine metabolism in humans and has a powerful antioxidant effect. The lack of ascorbic acid, known as vitamin C, in hominoids has been thought to cause a compensatory increase in uric acid as an antioxidant by unfunctional gene mutation of uricase to a pseudogene. Because XO is involved in an increase in reactive oxygen species (ROS) by generating superoxide and hydrogen peroxide, inadequate activation of XOR promotes oxidative stress-related tissue injury. Plasma XOR activity is associated with obesity, smoking, liver dysfunction, hyperuricemia, dyslipidemia, insulin resistance, and adipokines, indicating a novel biomarker of metabolic disorders. However, XOR activity in adipose tissue is low in humans unlike in rodents, and hypoxanthine is secreted from human adipose tissue. The concentration of hypoxanthine, but not xanthine, is independently associated with obesity in a general population, indicating differential regulation of hypoxanthine and xanthine. Treatment with an XOR inhibitor can decrease uric acid for preventing gout, reduce production of XO-related ROS, and promote reutilization of hypoxanthine and ATP production through the salvage pathway. It has recently been suggested that discontinuation of an XOR inhibitor causes adverse cardiovascular outcomes as XOR inhibitor withdrawal syndrome, possibly due to cardiac disturbance of conduction and contraction by reduced ATP production. New insights into purine metabolism, including the role of XOR activity in the past 5 yr, are mainly discussed in this review.
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2.
Cancer Cachexia and Related Metabolic Dysfunction.
Fonseca, GWPD, Farkas, J, Dora, E, von Haehling, S, Lainscak, M
International journal of molecular sciences. 2020;(7)
Abstract
Cancer cachexia is a complex multifactorial syndrome marked by a continuous depletion of skeletal muscle mass associated, in some cases, with a reduction in fat mass. It is irreversible by nutritional support alone and affects up to 74% of patients with cancer-dependent on the underlying type of cancer-and is associated with physical function impairment, reduced response to cancer-related therapy, and higher mortality. Organs, like muscle, adipose tissue, and liver, play an important role in the progression of cancer cachexia by exacerbating the pro- and anti-inflammatory response initially activated by the tumor and the immune system of the host. Moreover, this metabolic dysfunction is produced by alterations in glucose, lipids, and protein metabolism that, when maintained chronically, may lead to the loss of skeletal muscle and adipose tissue. Although a couple of drugs have yielded positive results in increasing lean body mass with limited impact on physical function, a single therapy has not lead to effective treatment of this condition. Therefore, a multimodal intervention, including pharmacological agents, nutritional support, and physical exercise, may be a reasonable approach for future studies to better understand and prevent the wasting of body compartments in patients with cancer cachexia.
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3.
Dietary linoleic acid and human health: Focus on cardiovascular and cardiometabolic effects.
Marangoni, F, Agostoni, C, Borghi, C, Catapano, AL, Cena, H, Ghiselli, A, La Vecchia, C, Lercker, G, Manzato, E, Pirillo, A, et al
Atherosclerosis. 2020;:90-98
Abstract
This narrative review aims to discuss the more relevant evidence on the role of linoleic acid (LA), a n-6 essential fatty acid that constitutes the predominant proportion of dietary polyunsaturated fatty acids (PUFA), in cardiovascular health. Although LA can be metabolized into Arachidonic Acid (AA), a 20 carbon PUFA which is the precursor of eicosanoids, including some with proinflammatory or prothrombotic-vasoconstrictor action, the large majority of experimental and clinical studies have assessed the potential benefit of increasing dietary intake of LA. Overall, data from clinical studies and meta-analyses suggest an association between high dietary intakes or tissue levels of n-6 PUFA, and specifically LA, and the improvement of cardiovascular risk (mainly of the plasma lipid profile), as well as long-term glycaemic control and insulin resistance. Most observational data show that elevated/increased dietary intake or tissue levels of LA is associated with a reduced incidence of cardiovascular diseases (mainly coronary artery diseases) and of new onset metabolic syndrome or type 2 diabetes. The effects of LA (or n-6 PUFA) in other physio-pathological areas are less clear. High quality clinical trials are needed to assess both the actual amplitude and the underlying mechanisms of the health effects related to dietary intake of this essential fatty acid.
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4.
Pearls and Pitfalls of Metabolic Liver Magnetic Resonance Imaging in the Pediatric Population.
Mojtahed, A, Gee, MS, Yokoo, T
Seminars in ultrasound, CT, and MR. 2020;(5):451-461
Abstract
Recent advances in magnetic resonance imaging (MRI) technology have moved imaging beyond anatomical assessment to characterization of tissue composition. There are now clinically validated MRI-based quantitative techniques for assessing liver fat, iron, and fibrosis, and MRI is now routinely used in metabolic liver disease evaluation in both pediatric and adult patients. These MRI techniques provide noninvasive quantitation of liver metabolic biomarkers that are increasingly relied upon in the clinical management of pediatric patients with nonalcoholic fatty liver disease, metabolic syndrome, and hemochromatosis and/or hemosiderosis. This article provides a review of the clinical indications and technical parameters for performing metabolic liver MRI in the pediatric population, along with common pearls and pitfalls encountered during its performance.
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5.
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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6.
Effects of sympathetic modulation in metabolic disease.
Carnagarin, R, Lambert, GW, Kiuchi, MG, Nolde, JM, Matthews, VB, Eikelis, N, Lambert, EA, Schlaich, MP
Annals of the New York Academy of Sciences. 2019;(1):80-89
Abstract
Sympathetic overdrive contributes to the derangement of glucose metabolism evident in clinical conditions, such as obesity, metabolic syndrome, type 2 diabetes, obstructive sleep apnea, and others. Targeting the sympathetic nervous system directly therefore appears as an attractive therapeutic approach to restore impaired glucose metabolism. Indeed, lifestyle interventions, including healthier diets and exercise, have been shown to exert their beneficial effects at least in part by reducing sympathetic nervous system activity. Pharmacologic inhibition of exaggerated central sympathetic outflow has also been demonstrated to beneficially impact on body weight and glucose and lipid metabolism. More recently, catheter-based renal denervation, an intervention applied predominantly to lower elevated blood pressure in patients with resistant hypertension, revealed salutary effects on glucose metabolism. Here, we review the mechanisms that contribute to the beneficial effects of targeting the sympathetic nervous system directly and discuss how these approaches may best be embedded in routine clinical practice.
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7.
Vitamin D and Cardio-Metabolic Risk Factors in Overweight Adults: An Overview of the Evidence.
Valer-Martinez, A, Martinez, JA, Sayon-Orea, C, Galvano, F, Grosso, G, Bes-Rastrollo, M
Current pharmaceutical design. 2019;(22):2407-2420
Abstract
BACKGROUND Several studies have suggested a potential association between low vitamin D serum levels and several pathological conditions apart from the well-known bone disorders. Thus, vitamin D insufficiency has been linked to cardiometabolic risk factors including obesity, insulin resistance, hypertension, dyslipidemia, as well as type 2 diabetes and cardiovascular disease. OBJECTIVE This review intends to provide an overview of recent evidence from clinical studies on vitamin D [25- hydroxyvitamin D (25(OH)D)] and cardiometabolic risk factors in overweight adults. Furthermore, we also discussed potential mechanisms and limits of the retrieved results. METHODS The search process was based on the selection of publications (RCT) listed in PubMed and Cochrane Library databases. RESULTS Vitamin D status evidenced an inversely strong association with subcutaneous adipose tissue and visceral adiposity, but not significantly related to other bodyweight measures (i.e., body mass index). Studies have shown a potential inverse association of hypovitaminosis D with insulin resistance and cardiovascular risk factors. CONCLUSION The mechanisms by which vitamin D deficiency enhances adiposity, as well as putative association with metabolic syndrome features, remain still unclear. Further investigation would be required to conclude whether vitamin D has an independent role in preventing cardiometabolic disorders.
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8.
Trypsin inhibitors: promising candidate satietogenic proteins as complementary treatment for obesity and metabolic disorders?
Cristina Oliveira de Lima, V, Piuvezam, G, Leal Lima Maciel, B, Heloneida de Araújo Morais, A
Journal of enzyme inhibition and medicinal chemistry. 2019;(1):405-419
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Abstract
The increase in non-communicable chronic diseases has aroused interest in the research of adjuvants to the classic forms of treatments. Obesity and metabolic syndrome are the main targets of confrontation because they relate directly to other chronic diseases. In this context, trypsin inhibitors, molecules with wide heterologous application, appear as possibilities in the treatment of overweight and obesity due to the action on satiety related mechanisms, mainly in the modulation of satiety hormones, such as cholecystokinin. In addition, trypsin inhibitors have the ability to also act on some biochemical parameters related to these diseases, thus, emerging as potential candidates and promising molecules in the treatment of the obesity and metabolic syndrome. Thus, the present article proposes to approach, through a systematic literature review, the advantages, disadvantages and viabilities for the use of trypsin inhibitors directed to the treatment of overweight and obesity.
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The Role of Autophagy in Systemic Metabolism and Human-Type Diabetes.
Kim, J, Lim, YM, Lee, MS
Molecules and cells. 2018;(1):11-17
Abstract
Autophagy is critical for the maintenance of organelle function and intracellular nutrient environment. Autophagy is also involved in systemic metabolic homeostasis, and its dysregulation can lead to or accelerate the development of metabolic disorders. While the role of autophagy in the global metabolism of model organisms has been investigated mostly using site-specific genetic knockout technology, the impact of dysregulated autophagy on systemic metabolism has been unclear. Here, we review recent papers showing the role of autophagy in systemic metabolism and in the development of metabolic disorders. Also included are data suggesting the role of autophagy in human-type diabetes, which are different in several key aspects from murine models of diabetes. The results shown here support the view that autophagy modulation could be a new modality for the treatment of metabolic syndrome associated with lipid overload and human-type diabetes.