scholarly journals Cbl Proto-Oncogene B (CBLB) c.197A>T Mutation Induces Mild Metabolic Dysfunction in Partial Type I Multiple Symmetric Lipomatosis (MSL)

2020 ◽  
Vol Volume 13 ◽  
pp. 3535-3549
Author(s):  
Ke Chen ◽  
Xinxing Wan ◽  
Liling Zhao ◽  
Shaoli Zhao ◽  
Lin Peng ◽  
...  
Keyword(s):  
Type I ◽  
Metabolic Dysfunction ◽  
Multiple Symmetric Lipomatosis ◽  
Partial Type

scholarly journals Adipose type I interferon signalling protects against metabolic dysfunction

2017 ◽  
Vol 66 (1) ◽  
pp. S609
Author(s):  
T. Adolph ◽  
V. Wieser ◽  
C. Grander ◽  
F. Grabherr ◽  
B. Enrich ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Type I ◽  
Metabolic Dysfunction ◽  
Interferon Signalling

scholarly journals Type I interferon potentiates metabolic dysfunction, inflammation, and accelerated aging in mtDNA mutator mice

2020 ◽  
Author(s):  
Yuanjiu Lei ◽  
Camila Guerra Martinez ◽  
Sylvia Torres-Odio ◽  
Samantha L. Bell ◽  
Christine E. Birdwell ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Inflammatory Responses ◽  
Type I Interferon ◽  
Aerobic Glycolysis ◽  
Accelerated Aging ◽  
Innate Immune ◽  
Related Factor ◽  
Type I ◽  
Metabolic Dysfunction ◽  
Polymerase Gamma

AbstractMitochondrial dysfunction is a key driver of inflammatory responses in human disease. However, it remains unclear whether alterations in mitochondria-innate immune crosstalk contribute to the pathobiology of mitochondrial disorders and aging. Using the polymerase gamma (POLG) mutator model of mitochondrial DNA (mtDNA) instability, we report that aberrant activation of the type I interferon (IFN-I) innate immune axis potentiates immunometabolic dysfunction, reduces healthspan, and accelerates aging in mutator mice. Mechanistically, elevated IFN-I signaling suppresses activation of nuclear factor erythroid 2-related factor 2 (Nrf2), which increases oxidative stress, enhances pro-inflammatory cytokine responses, and accelerates metabolic dysfunction. Ablation of IFN-I signaling attenuates hyper-inflammatory phenotypes by restoring Nrf2 activity and reducing aerobic glycolysis, which combine to lessen cardiovascular and myeloid dysfunction in aged mutator mice. These findings further advance our knowledge of how mitochondrial dysfunction shapes innate immune responses and provide a framework for understanding mitochondria-driven immunopathology in POLG-related diseases and aging.

scholarly journals Multiple symmetric lipomatosis type I in a female patient with neuropathy: no association with alcoholism or mitochondrial DNA m.8344A>G mutation

QJM ◽  
2012 ◽  
Vol 108 (6) ◽  
pp. 503-505 ◽  
Author(s):  
E. Pasmatzi ◽  
A. Monastirli ◽  
E. Chroni ◽  
S. Georgiou ◽  
J. Habeos ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Female Patient ◽  
Type I ◽  
Multiple Symmetric Lipomatosis

scholarly journals Exploring the Interplay Between Oral Diseases, Microbiome, and Chronic Diseases Driven by Metabolic Dysfunction in Childhood

2021 ◽  
Vol 2 ◽  
Author(s):  
Fernanda Maria Sabella ◽  
Simone Nataly Busato de Feiria ◽  
Apoena de Aguiar Ribeiro ◽  
Letícia Helena Theodoro ◽  
José Francisco Höfling ◽  
...  
Keyword(s):  
Chronic Diseases ◽  
Type I Diabetes ◽  
Oral Microbiome ◽  
Entire Body ◽  
Type I ◽  
Metabolic Dysfunction ◽  
Oral Diseases ◽  
Future Health ◽  
Childhood Diseases ◽  
Inflammatory State

Oral childhood diseases, such as caries and gingivitis, have much more than a local impact on the dentition and tooth surrounding tissues, which can affect systemic conditions. While the mouth is frequently exposed to microbial stressors that can contribute to an inflammatory state in the entire body, chronic disorders can also interfere with oral health. Sharing common risk factors, a dynamic interplay can be driven between 1. dental caries, gingivitis, and type I diabetes mellitus, 2. early childhood caries and obesity, and 3. caries and cardiovascular diseases. Considering that there are ~2.2 billion children worldwide and that childhood provides unique opportunities for intervention targeting future health promotion, this review is of prime importance and aimed to explore the relationship between the oral microbiome and oral chronic diseases driven by metabolic dysfunction in childhood.

scholarly journals Melatonin attenuates mitochondrial and metabolic dysfunction caused by leptin deficiency

2018 ◽  
Author(s):  
Yaiza Potes ◽  
Andrea Díaz-Luis ◽  
Juan C Bermejo-Millo ◽  
Zulema Pérez-Martínez ◽  
Beatriz de Luxán-Delgado ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Energy Production ◽  
Energy Homeostasis ◽  
Nutrient Sensing ◽  
Type I ◽  
Metabolic Dysfunction ◽  
Deficient Animal ◽  
Melatonin Treatment ◽  
Leptin Deficiency ◽  
Type Ii Fibers

AbstractLeptin, as a nutritional inhibitor by repressing food intake, is critical compromised in the major common forms of obesity. Skeletal muscle is the main effector tissue for energy expenditure modifications by the effect of endocrine axes, such as leptin signaling. Our study has been carried out using skeletal muscle from leptin-deficient animal model, in order to ascertain the importance of this hormone in eating disorders. Here we report that leptin-deficiency stimulates an uncontrolled oxidative phosphorylation metabolism, resulting in an excess of energy production that culminates in mitochondrial dysfunction. Thus, different nutrient sensing pathways are perturbed, loosing proteostasis and promoting lipid anabolism, that induces myofiber degeneration and drives oxidative type I fiber conversion. Melatonin treatment plays a significant role in regulating energy homeostasis and fuel utilization. This study reveals melatonin to be a decisive mitochondrial function-fate regulator, with implications for resembling physiological energy requirements and targeting glycolytic type II fibers recovery.

scholarly journals Exploration of the Diversity of Clustered Regularly Interspaced Short Palindromic Repeats-Cas Systems in Clostridium novyi sensu lato

2021 ◽  
Vol 12 ◽  
Author(s):  
Thibault Le Gratiet ◽  
Caroline Le Marechal ◽  
Marie Devaere ◽  
Marianne Chemaly ◽  
Cédric Woudstra
Keyword(s):  
Clostridium Botulinum ◽  
Type I ◽  
Group Iii ◽  
Clostridium Novyi ◽  
Associated Proteins ◽  
Partial Type ◽  
Type V ◽  
First Time ◽  
Restriction Modification ◽  
Shed Light

Classified as the genospecies Clostridium novyi sensu lato and distributed into four lineages (I–IV), Clostridium botulinum (group III), Clostridium novyi, and Clostridium haemolyticum are clostridial pathogens that cause animal diseases. Clostridium novyi sensu lato contains a large mobilome consisting of plasmids and circular bacteriophages. Here, we explored clustered regularly interspaced short palindromic repeats (CRISPR) arrays and their associated proteins (Cas) to shed light on the link between evolution of CRISPR-Cas systems and the plasmid and phage composition in a study of 58 Clostridium novyi sensu lato genomes. In 55 of these genomes, types I-B (complete or partial), I-D, II-C, III-B, III-D, or V-U CRISPR-Cas systems were detected in chromosomes as well as in mobile genetic elements (MGEs). Type I-B predominated (67.2%) and was the only CRISPR type detected in the Ia, III, and IV genomic lineages. Putative type V-U CRISPR Cas14a genes were detected in two different cases: next to partial type-IB CRISPR loci on the phage encoding the botulinum neurotoxin (BoNT) in lineage Ia and in 12 lineage II genomes, as part of a putative integrative element related to a phage-inducible chromosomal island (PICI). In the putative PICI, Cas14a was associated with CRISPR arrays and restriction modification (RM) systems as part of an accessory locus. This is the first time a PICI containing such locus has been detected in C. botulinum. Mobilome composition and dynamics were also investigated based on the contents of the CRISPR arrays and the study of spacers. A large proportion of identified protospacers (20.2%) originated from Clostridium novyi sensu lato (p1_Cst, p4_BKT015925, p6_Cst, CWou-2020a, p1_BKT015925, and p2_BKT015925), confirming active exchanges within this genospecies and the key importance of specific MGEs in Clostridium novyi sensu lato.

scholarly journals Elevated type I interferon responses potentiate metabolic dysfunction, inflammation, and accelerated aging in mtDNA mutator mice

2021 ◽  
Vol 7 (22) ◽  
pp. eabe7548
Author(s):  
Yuanjiu Lei ◽  
Camila Guerra Martinez ◽  
Sylvia Torres-Odio ◽  
Samantha L. Bell ◽  
Christine E. Birdwell ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Inflammatory Responses ◽  
Type I Interferon ◽  
Aerobic Glycolysis ◽  
Accelerated Aging ◽  
Innate Immune ◽  
Related Factor ◽  
Type I ◽  
Metabolic Dysfunction ◽  
Elevated Type

Mitochondrial dysfunction is a key driver of inflammatory responses in human disease. However, it remains unclear whether alterations in mitochondria-innate immune cross-talk contribute to the pathobiology of mitochondrial disorders and aging. Using the polymerase gamma (POLG) mutator model of mitochondrial DNA instability, we report that aberrant activation of the type I interferon (IFN-I) innate immune axis potentiates immunometabolic dysfunction, reduces health span, and accelerates aging in mutator mice. Mechanistically, elevated IFN-I signaling suppresses activation of nuclear factor erythroid 2–related factor 2 (NRF2), which increases oxidative stress, enhances proinflammatory cytokine responses, and accelerates metabolic dysfunction. Ablation of IFN-I signaling attenuates hyperinflammatory phenotypes by restoring NRF2 activity and reducing aerobic glycolysis, which combine to lessen cardiovascular and myeloid dysfunction in aged mutator mice. These findings further advance our knowledge of how mitochondrial dysfunction shapes innate immune responses and provide a framework for understanding mitochondria-driven immunopathology in POLG-related disorders and aging.

scholarly journals White Adipose Tissue Expansion in Multiple Symmetric Lipomatosis Is Associated with Upregulation of CK2, AKT and ERK1/2

2020 ◽  
Vol 21 (21) ◽  
pp. 7933
Author(s):  
Marta Sanna ◽  
Christian Borgo ◽  
Chiara Compagnin ◽  
Francesca Favaretto ◽  
Vincenzo Vindigni ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Stromal Vascular Fraction ◽  
Tissue Expansion ◽  
Specific Marker ◽  
Type I ◽  
Vitro Assay ◽  
Multiple Symmetric Lipomatosis ◽  
Paired Control ◽  
Subcutaneous Adipose

Multiple symmetric lipomatosis (MSL) is a rare disorder characterized by overgrowing lipomatous tissue (LT) in the subcutaneous adipose tissue (SAT). What LT is and how it expands are not completely understood; previous data suggested that it could derive from brown AT precursors. In six MSL type I patients, we compared LT morphology by histological and immunohistochemistry (IHC) analysis, gene expression, by qPCR, kinase activity, by Western Blot and in vitro assay to paired-control SAT using AT from patients with pheochromocytoma as a human browning reference. In the stromal vascular fraction (SVF), we quantified adipose stem cells (ASCs) by flow cytometry, the proliferation rate, white and beige adipogenic potential and clonogenicity and adipogenicity by a limiting dilution assay. LT displayed white AT morphology and expression pattern and did not show increased levels of the brown-specific marker UCP1. In LT, we evidenced AKT, CK2 and ERK1/2 hyperactivation. LT-SVF contained increased ASCs, proliferated faster, sprouted clones and differentiated into adipocytes better than the control, displaying enhanced white adipogenic potential but not increased browning compared to SAT. In conclusion, LT is a white AT depot expanding by hyperplasia through increased stemness and enhanced white adipogenesis upregulating AKT, CK2 and ERK1/2, which could represent new targets to counteract MSL.

scholarly journals Aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent manner

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria E. Moreno-Fernandez ◽  
Vishakha Sharma ◽  
Traci E. Stankiewicz ◽  
Jarren R. Oates ◽  
Jessica R. Doll ◽  
...  
Keyword(s):  
Severe Obesity ◽  
Type I ◽  
Metabolic Dysfunction ◽  
Housing Conditions ◽  
Independent Manner ◽  
Alcoholic Fatty Liver ◽  
Female Mice ◽  
Inflammatory Pathways ◽  
Feeding Regimen ◽  
The Impact

Abstract Background Understanding gender-associated bias in aging and obesity-driven metabolic derangements has been hindered by the inability to model severe obesity in female mice. Methods Here, using chow- or high fat diet (HFD)-feeding regimens at standard (TS) and thermoneutral (TN) housing temperatures, the latter to model obesity in female mice, we examined the impact of gender and aging on obesity-associated metabolic derangements and immune responsiveness. Analysis included quantification of: (i) weight gain and adiposity; (ii) the development and severity of glucose dysmetabolism and non-alcoholic fatty liver disease (NAFLD); and (iii) induction of inflammatory pathways related to metabolic dysfunction. Results We show that under chow diet feeding regimen, aging was accompanied by increased body weight and white adipose tissue (WAT) expansion in a gender independent manner. HFD feeding regimen in aged, compared to young, male mice at TS, resulted in attenuated glucose dysmetabolism and hepatic steatosis. However, under TS housing conditions only aged, but not young, HFD fed female mice developed obesity. At TN however, both young and aged HFD fed female mice developed severe obesity. Independent of gender or housing conditions, aging attenuated the severity of metabolic derangements in HFD-fed obese mice. Tempered severity of metabolic derangements in aged mice was associated with increased splenic frequency of regulatory T (Treg) cells, Type I regulatory (Tr1)-like cells and circulating IL-10 levels and decreased vigor of HFD-driven induction of inflammatory pathways in adipose and liver tissues. Conclusion Our findings suggest that aging-associated altered immunological profile and inflammatory vigor may play a dominant role in the attenuation of obesogenic diet-driven metabolic dysfunction.

Heat-Etching with a Bullivant Type II Simple Freeze-Cleave Device

1970 ◽  
Vol 28 ◽  
pp. 106-107 ◽  
Author(s):  
Ronald S. Weinstein ◽  
N. Scott McNutt
Keyword(s):  
New Zealand ◽  
General Hospital ◽  
Massachusetts General Hospital ◽  
Type I ◽  
Type Ii ◽  
Collaborative Effort ◽  
Temperature And Pressure ◽  
The University

The Type I simple cold block device was described by Bullivant and Ames in 1966 and represented the product of the first successful effort to simplify the equipment required to do sophisticated freeze-cleave techniques. Bullivant, Weinstein and Someda described the Type II device which is a modification of the Type I device and was developed as a collaborative effort at the Massachusetts General Hospital and the University of Auckland, New Zealand. The modifications reduced specimen contamination and provided controlled specimen warming for heat-etching of fracture faces. We have now tested the Mass. General Hospital version of the Type II device (called the “Type II-MGH device”) on a wide variety of biological specimens and have established temperature and pressure curves for routine heat-etching with the device.

Sign in / Sign up

Export Citation Format

Share Document