Knockout of the non-essential gene SUGCT creates diet-linked, age-related microbiome disbalance with a diabetes-like metabolic syndrome phenotype.

Knockout of the non-essential gene SUGCT creates diet-linked, age-related microbiome disbalance with a diabetes-like metabolic syndrome phenotype. Cell Mol Life Sci. 2019 Nov 13;: Authors: Niska-Blakie J, Gopinathan L, Low KN, Kien YL, Goh CMF, Caldez MJ, Pfeiffenberger E, Jones OS, Ong CB, Kurochkin IV, Coppola V, Tessarollo L, Choi H, Kanagasundaram Y, Eisenhaber F, Maurer-Stroh S, Kaldis P Abstract SUGCT (C7orf10) is a mitochondrial enzyme that synthesizes glutaryl-CoA from glutarate in tryptophan and lysine catabolism, but it has not been studied in vivo. Although mutations in Sugct lead to Glutaric Aciduria Type 3 disease in humans, patients remain largely asymptomatic despite high levels of glutarate in the urine. To study the disease mechanism, we generated SugctKO mice and uncovered imbalanced lipid and acylcarnitine metabolism in kidney in addition to changes in the gut microbiome. After SugctKO mice were treated with antibiotics, metabolites were comparable to WT, indicating that the microbiome affects metabolism in SugctKO mice. SUGCT loss of function contributes to gut microbiota dysbiosis, leading to age-dependent pathological changes in kidney, liver, and adipose tissue. This is associated with an obesity-related phenotype that is accompanied by lipid accumulation in kidney and liver, as well as "crown-like" structures in adipocytes. Furthermore, we show that the SugctKO kidney pathology is accelerated and exacerbated by a high-ly...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research

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Metabolic syndrome, characterized by central obesity, hypertension, and hyperlipidemia, increases the morbidity and mortality of cardiovascular disease, type 2 diabetes, nonalcoholic fatty liver disease, and other metabolic diseases. It is well known that insulin resistance, especially hepatic insulin resistance, is a risk factor for metabolic syndrome. Current research has shown that hepatic fatty acid accumulation can cause hepatic insulin resistance through increased gluconeogenesis, lipogenesis, chronic inflammation, oxidative stress and endoplasmic reticulum stress, and impaired insulin signal pathway. Mitochondria ar...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
AbstractIt is well recognized that the decrease of adiponectin associated with high-fat diet and lack of exercise accounts for the onset of insulin resistance, type 2 diabetes, the metabolic syndrome, and cardiovascular disease. Our research efforts have led to the identification of adiponectin receptors, AdipoR1 and AdipoR2, with the former shown to activate AMP kinase in the liver and the latter shown to activate peroxisome proliferator-activated receptor- α signaling thereby increasing fatty acid oxidation. Again, adiponectin upregulates mitochondrial function in the skeletal muscle thereby improving glucose/lipid...
Source: Diabetology International - Category: Endocrinology Source Type: research
Abstract Cellular damage produced by conditions generating oxidative stress have far-reaching implications in human disease that encompass, but are not restricted to aging, cardiovascular disease, type 2 diabetes, airway inflammation/asthma, cancer, and metabolic syndrome including visceral obesity, insulin resistance, fatty liver disease, and dyslipidemia. Although there are numerous sources and cellular targets of oxidative stress, this review will highlight literature that has investigated downstream consequences of oxidatively-induced DNA damage in both nuclear and mitochondrial genomes. The presence of such d...
Source: DNA Repair - Category: Genetics & Stem Cells Authors: Tags: DNA Repair (Amst) Source Type: research
In this study, we determine whether transient reintroduction of embryonic stem cell cycle miR-294 promotes cardiomyocyte cell cycle reentry enhancing cardiac repair after myocardial injury. A doxycycline-inducible AAV9-miR-294 vector was delivered to mice for activating miR-294 in myocytes for 14 days continuously after myocardial infarction. miR-294-treated mice significantly improved left ventricular functions together with decreased infarct size and apoptosis 8 weeks after MI. Myocyte cell cycle reentry increased in miR-294 hearts parallel to increased small myocyte number in the heart. Isolated adult myocytes from miR-...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusions Two, Not Mutually Exclusive, Hypotheses We have reviewed and organized the literature with the intent of showing the existing parallels between excessive fat accumulation and the aging process. We have categorized these reports following what have been proposed to be the nine hallmarks of aging (21) (Figure 1). Based on the evidence, two distinct hypotheses can be proposed. One is that the cellular responses provoked by an excess of nutrients cause obesity, and that obesity is responsible for accelerating the pace of aging. Supporting this hypothesis are the observations that knocking out the fat-specific ins...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Dominique E. Martin1,2, Amanda K. Jones1,3, Sambhu M. Pillai1,4, Maria L. Hoffman1,5, Katelyn K. McFadden1,6, Steven A. Zinn1, Kristen E. Govoni1 and Sarah A. Reed1* 1Department of Animal Science, University of Connecticut, Storrs, CT, United States 2Department of Psychology, Providence College, Providence, RI, United States 3Department of Pediatrics, School of Medicine, University of Colorado, Aurora, Aurora, CO, United States 4School of Medicine, Georgetown University, Washington, DC, United States 5Department of Fisheries, Animal and Veterinary Sciences, The University of Rhode Island, Kingston, RI, United St...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Conclusion: 3T3-L1 cells, treated with LPV/RTV, show altered lipid content due to increased miRNA-218 levels, which affects lipin-1 mRNA. Moreover, increased miRNA-218 levels were inversely correlated with changes in GLUT-4 expression, which suggests a role for miRNA-218 in mediating the insulin resistance consequent to cART. Introduction Metabolic syndrome is a serious consequence of combined Antiretroviral Therapy (cART). HIV-associated metabolic syndrome is often accompanied by lipodystrophy (LS), the redistribution of body fat with loss of subcutaneous adipose tissue in face, limbs and buttocks, concomitant wit...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In conclusion, TSF improved lipid accumulation and hepatic steatosis by inducing the AMPK/SIRT1 pathway-mediated autophagy. Introduction Nonalcoholic fatty liver disease (NAFLD) has become a worldwide health concern due to the increased incidence of obesity and diabetes. In addition, NAFLD is closely associated with the risk factors of coronary heart disease, such as metabolic syndrome, diabetes mellitus, and dyslipidemia, which are considered to be the leading causes of death (Wiest et al., 2017). Although our understanding of the pathogenesis of NAFLD has significantly improved, there is still no effective medica...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
We examined the effects of the independent and combined effects of Zataria Multiflora supplementation and circuit resistance training (CRT) on selected adipokines among postmenopausal women. Forty-eight postmenopausal women were divided into four groups: Exercise (EG, n = 12), Zataria Multiflora (ZMG, n = 12), exercise and Zataria Multiflora (ZMEG, n = 12), and control (CG, n = 12). Participants in experimental groups either performed CRT (3 sessions per week with intensity at 55% of one-repetition maximum) or supplemented with Zataria Multiflora (500 mg every day after breakfast with 100 ml of water), or their combination...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Conclusion Taken together, evidence from animal and human studies demonstrates that the brain detects levels of circulating nutrients and hormones and consequently organizes an outward response that contributes to the regulation of whole-body glucose homeostasis. However, there are major knowledge gaps about the exact nature of this response and its relative importance compared to peripheral processes. As we have seen, animal studies have provided an anatomical map of CNS glucose regulation and have identified important neurons and neural circuits involved. Additionally, the CNS sensing of key nutrients and hormones has b...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
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