A conserved role of the insulin-like signaling pathway in diet-dependent uric acid pathologies in Drosophila melanogaster

by Sven Lang, Tyler A. Hilsabeck, Kenneth A. Wilson, Amit Sharma, Neelanjan Bose, Deanna J. Brackman, Jennifer N. Beck, Ling Chen, Mark A. Watson, David W. Killilea, Sunita Ho, Arnold Kahn, Kathleen Giacomini, Marshall L. Stoller, Thomas Chi, Pankaj Kapahi Elevated uric acid (UA) is a key risk factor for many disorders, including metabolic syndrome, gout and kidney stones. Despite frequent occurrence of these disorders, the genetic pathways influencing UA metabolism and the association with disease remain poorly understood. In humans, elevated UA le vels resulted from the loss of the of the urate oxidase (Uro) gene around 15 million years ago. Therefore, we established aDrosophila melanogaster model with reduced expression of the orthologousUro gene to study the pathogenesis arising from elevated UA. ReducedUro expression inDrosophila resulted in elevated UA levels, accumulation of concretions in the excretory system, and shortening of lifespan when reared on diets containing high levels of yeast extract. Furthermore, high levels of dietary purines, but not protein or sugar, were sufficient to produce the same effects of shortened lifespan and concretion formation in theDrosophila model. The insulin-like signaling (ILS) pathway has been shown to respond to changes in nutrient status in several species. We observed that genetic suppression of ILS genes reduced both UA levels and concretion load in flies fed high levels of yeast extract. Further support for the role of the ILS...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research

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Conclusion: This study confirmed the association of vitamin D deficiency with hypothyroidism, thyroid autoimmunity, increased volume, nodularity, and vascularity of thyroid gland in hypothyroid patients as well as increased HOMA-IR. It proved the association between HOMA-IR and thyroid autoimmunity. The study proved no association between VDR polymorphisms (Fok1 and Apa1) with either vitamin D levels or TSH levels. PMID: 31534663 [PubMed]
Source: Journal of Thyroid Research - Category: Endocrinology Tags: J Thyroid Res Source Type: research
"Gut Microbiota-Circadian Clock Axis" in Deciphering the Mechanism Linking Early-Life Nutritional Environment and Abnormal Glucose Metabolism. Int J Endocrinol. 2019;2019:5893028 Authors: Zhou L, Kang L, Xiao X, Jia L, Zhang Q, Deng M Abstract The prevalence of diabetes mellitus (DM) has been increasing dramatically worldwide, but the pathogenesis is still unknown. A growing amount of evidence suggests that an abnormal developmental environment in early life increases the risk of developing metabolic diseases in adult life, which is referred to as the "metabolic memory" and the Deve...
Source: International Journal of Endocrinology - Category: Endocrinology Tags: Int J Endocrinol Source Type: research
Abstract Purine metabolism in the circulatory system yields uric acid as its final oxidation product, which is believed to be linked to the development of gout and kidney stones. Hyperuricemia is closely correlated with cardiovascular disease, metabolic syndrome, and chronic kidney disease, as attested by epidemiological and empirical research. In this review, we summarize the recent knowledge about hyperuricemia, with a special focus on its physiology, epidemiology, and correlation with cardiovascular disease. This review also discusses the possible positive effects of treatment to reduce urate levels in patients...
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
AbstractObjectiveTo clarify the clinical and laboratory characteristics of nephrolithiasis in gout by computed tomography (CT).MethodsIn 350 gout patients, unenhanced CT was performed at the 1st visit to hospital. Calculus density spots exceeding 1  mm in diameter with a CT value>120 Hounsfield units in the kidneys were defined as kidney stones. The association between laterality and the number of stones was investigated in each stone carrier. The 350 patients were classified into three groups (bilateral, unilateral and non ‐stone carriers). Then serum urate (Sua), renal function, uric acid metabolism, and the pr...
Source: APLAR Journal of Rheumatology - Category: Rheumatology Authors: Tags: ORIGINAL ARTICLE Source Type: research
Authors: Palazzuoli A, Hashemi H, Jameson LC, McCullough PA Abstract Uric acid (UA), the metabolic mediator of gout and urate renal stones, is associated with increased cardiovascular risk burden. Hyperuricemia is a common metabolic disorder, and interaction among UA and cardiovascular diseases has been clearly described. Several illnesses, including hypertension, myocardial infarction, metabolic syndrome, and heart failure, are related to increases in UA levels. In this article, we discuss the pathophysiology of hyperuricemia and describe the biologic plausibility of this metabolite's participation in the pathogen...
Source: Reviews in Cardiovascular Medicine - Category: Cardiology Tags: Rev Cardiovasc Med Source Type: research
Publication date: June 2018Source: American Journal of Kidney Diseases, Volume 71, Issue 6Author(s): Richard J. Johnson, George L. Bakris, Claudio Borghi, Michel B. Chonchol, David Feldman, Miguel A. Lanaspa, Tony R. Merriman, Orson W. Moe, David B. Mount, Laura Gabriella Sanchez Lozada, Eli Stahl, Daniel E. Weiner, Glenn M. ChertowUrate is a cause of gout, kidney stones, and acute kidney injury from tumor lysis syndrome, but its relationship to kidney disease, cardiovascular disease, and diabetes remains controversial. A scientific workshop organized by the National Kidney Foundation was held in September 2016 to review c...
Source: American Journal of Kidney Diseases - Category: Urology & Nephrology Source Type: research
Abstract Gout is an inflammatory disease manifested by the deposition of monosodium urate (MSU) crystals in joints, cartilage, synovial bursa, tendons or soft tissues. Gout is not a new disease, which was first documented nearly 5,000 years ago. The prevalence of gout has increased globally in recent years, imposing great disease burden worldwide. Moreover, gout or hyperuricemia is clearly associated with a variety of comorbidities, including cardiovascular diseases, chronic kidney disease, urolithiasis, metabolic syndrome, diabetes mellitus, thyroid dysfunction, and psoriasis. To prevent acute arthritis attacks and compli...
Source: APLAR Journal of Rheumatology - Category: Rheumatology Authors: Tags: Review Article Source Type: research
Authors: Abrahams MN Abstract Gout is the most common crystal arthritis and its prevalence is rising. It is associated with the metabolic syndrome, and hyperuricaemia may be an independent risk factor for cardiovascular disease. The acute presentation of gout is easily managed, but the underlying cause is seldom addressed.Indications for initiating uric acid therapy have been clearly established. The classification criteria for gout have been reviewed and are presented here.Lifestyle modification is key to the management of gout. The clinician must screen for diabetes, hypertension and hypercholesterolaemia when th...
Source: South African Medical Journal - Category: African Health Tags: S Afr Med J Source Type: research
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