scholarly journals Apolipoprotein A5 controls fructose-induced metabolic dysregulation in mice

2020 ◽  
Author(s):  
Claudia Ress ◽  
Jochen Dobner ◽  
Kerstin Rufinatscha ◽  
Bart Staels ◽  
Maximilian Hofer ◽  
...  
Keyword(s):  
Apolipoprotein A5 ◽  
Metabolic Dysregulation

Dual role of B7 costimulation in obesity-related non-alcoholic steatohepatitis (NASH) and metabolic dysregulation

2014 ◽  
Vol 122 (03) ◽  
Author(s):  
A Chatzigeorgiou ◽  
R Garcia-Martin ◽  
KJ Chung ◽  
I Alexaki ◽  
A Klotzsche-von Ameln ◽  
...  
Keyword(s):  
Dual Role ◽  
Alcoholic Steatohepatitis ◽  
Metabolic Dysregulation

Mutations of the Apolipoprotein A5 Gene with Inherited Hypertriglyceridaemia: Review of the Current Literature

2012 ◽  
Vol 19 (36) ◽  
pp. 6163-6170 ◽  
Author(s):  
B. I. Melegh ◽  
B. Duga ◽  
K. Sumegi ◽  
P. Kisfali ◽  
A. Maasz ◽  
...  
Keyword(s):  
Current Literature ◽  
Apolipoprotein A5

scholarly journals Activation of mitochondrial TUFM ameliorates metabolic dysregulation through coordinating autophagy induction

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Dasol Kim ◽  
Hui-Yun Hwang ◽  
Eun Sun Ji ◽  
Jin Young Kim ◽  
Jong Shin Yoo ◽  
...  
Keyword(s):  
Metabolic Regulation ◽  
Elongation Factor ◽  
Dependent Manner ◽  
Diet Induced Obesity ◽  
Metabolic Dysregulation ◽  
Autophagy Induction ◽  
Transcription Factor Eb ◽  
Mitochondrial Elongation

AbstractDisorders of autophagy, a key regulator of cellular homeostasis, cause a number of human diseases. Due to the role of autophagy in metabolic dysregulation, there is a need to identify autophagy regulators as therapeutic targets. To address this need, we conducted an autophagy phenotype-based screen and identified the natural compound kaempferide (Kaem) as an autophagy enhancer. Kaem promoted autophagy through translocation of transcription factor EB (TFEB) without MTOR perturbation, suggesting it is safe for administration. Moreover, Kaem accelerated lipid droplet degradation in a lysosomal activity-dependent manner in vitro and ameliorated metabolic dysregulation in a diet-induced obesity mouse model. To elucidate the mechanism underlying Kaem’s biological activity, the target protein was identified via combined drug affinity responsive target stability and LC–MS/MS analyses. Kaem directly interacted with the mitochondrial elongation factor TUFM, and TUFM absence reversed Kaem-induced autophagy and lipid degradation. Kaem also induced mitochondrial reactive oxygen species (mtROS) to sequentially promote lysosomal Ca2+ efflux, TFEB translocation and autophagy induction, suggesting a role of TUFM in mtROS regulation. Collectively, these results demonstrate that Kaem is a potential therapeutic candidate/chemical tool for treating metabolic dysregulation and reveal a role for TUFM in autophagy for metabolic regulation with lipid overload.

Phenylalanine Metabolism is Dysregulated in Human Hippocampus with Alzheimer’s Disease Related Pathological Changes

2021 ◽  
pp. 1-14
Author(s):  
Pan Liu ◽  
Qian Yang ◽  
Ning Yu ◽  
Yan Cao ◽  
Xue Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Pathological Examination ◽  
Pathological Changes ◽  
Targeted Metabolomics ◽  
Phenylpyruvic Acid ◽  
Postmortem Human Brain ◽  
Metabolic Dysregulation ◽  
Phenylalanine Metabolism

Background: Alzheimer’s disease (AD) is one of the most challenging diseases causing an increasing burden worldwide. Although the neuropathologic diagnosis of AD has been established for many years, the metabolic changes in neuropathologic diagnosed AD samples have not been fully investigated. Objective: To elucidate the potential metabolism dysregulation in the postmortem human brain samples assessed by AD related pathological examination. Methods: We performed untargeted and targeted metabolomics in 44 postmortem human brain tissues. The metabolic differences in the hippocampus between AD group and control (NC) group were compared. Results: The results show that a pervasive metabolic dysregulation including phenylalanine metabolism, valine, leucine, and isoleucine biosynthesis, biotin metabolism, and purine metabolism are associated with AD pathology. Targeted metabolomics reveal that phenylalanine, phenylpyruvic acid, and N-acetyl-L-phenylalanine are upregulated in AD samples. In addition, the enzyme IL-4I1 catalyzing transformation from phenylalanine to phenylpyruvic acid is also upregulated in AD samples. Conclusion: There is a pervasive metabolic dysregulation in hippocampus with AD-related pathological changes. Our study suggests that the dysregulation of phenylalanine metabolism in hippocampus may be an important pathogenesis for AD pathology formation.

scholarly journals IL4-10 Fusion Protein Shows DMOAD Activity in a Rat Osteoarthritis Model

Cartilage ◽  
2021 ◽  
pp. 194760352110267
Author(s):  
E.M. van Helvoort ◽  
H.M. de Visser ◽  
F.P.J.G. Lafeber ◽  
K. Coeleveld ◽  
S. Versteeg ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Single Molecule ◽  
Mechanical Allodynia ◽  
Cartilage Damage ◽  
Cartilage Degeneration ◽  
Synovial Inflammation ◽  
Interleukin 4 ◽  
Analgesic Effects ◽  
Metabolic Dysregulation ◽  
Anti Inflammatory

Objective Ideally, disease-modifying osteoarthritis (OA) drugs (DMOAD) should combine chondroprotective, anti-inflammatory, and analgesic effects in a single molecule. A fusion protein of interleukin-4 (IL-4) and IL-10 (IL4-10 FP) possesses these combined effects. In this study, the DMOAD activity of rat IL4-10 FP (rIL4-10 FP) was tested in a rat model of surgically induced OA under metabolic dysregulation. Design rIL4-10 FP was produced with HEK293F cells. Bioactivity of purified rIL4-10 FP was determined in a whole blood assay. Male Wistar rats ( n = 20) were fed a high-fat diet (HFD) to induce metabolic dysregulation. After 12 weeks, OA was induced according to the Groove model. Two weeks after OA induction, rats were randomly divided into 2 groups and treated with 10 weekly, intra-articular injections of either rIL4-10 FP ( n = 10) or phosphate buffered saline (PBS; n = 10). Possible antibody formation was evaluated using ELISA, cartilage degeneration and synovial inflammation were evaluated by histology and mechanical allodynia was evaluated using the von Frey test. Results Intra-articular injections with rIL4-10 FP significantly reduced cartilage degeneration ( P = 0.042) and decreased mechanical allodynia ( P < 0.001) compared with PBS. Only mild synovial inflammation was found (nonsignificant), limiting detection of putative anti-inflammatory effects. Multiple injections of rIL4-10 FP did not induce antibodies against rIL4-10 FP. Conclusion rIL4-10 FP showed chondroprotective and analgesic activity in a rat OA model with moderate cartilage damage, mild synovial inflammation, and pain. Future studies will need to address whether less frequent intra-articular injections, for example, with formulations with increased residence time, would also lead to DMOAD activity.

scholarly journals EXPRESS: What’s New in Pulmonary Hypertension Clinical Research: Lessons from the Best Abstracts at the 2020 American Thoracic Society International Conference

2021 ◽  
pp. 204589402110407
Author(s):  
Andrew J Sweatt ◽  
Raju Reddy ◽  
Farbod Rahaghi ◽  
Nadine Al-Naamani
Keyword(s):  
Pulmonary Hypertension ◽  
Clinical Research ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
American Thoracic Society ◽  
Future Directions ◽  
International Conference ◽  
Metabolic Dysregulation ◽  
Current State ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial

In this conference paper, we review the 2020 American Thoracic Society (ATS) International Conference session titled, “What’s New in Pulmonary Hypertension Clinical Research: Lessons from the Best Abstracts”. This virtual mini-symposium took place on October 21, 2020, in lieu of the annual in-person ATS International Conference which was cancelled due to the COVID-19 pandemic. Seven clinical research abstracts were selected for presentation in the session, which encompassed five major themes: (1) standardizing diagnosis and management of pulmonary hypertension, (2) improving risk assessment in pulmonary arterial hypertension, (3) evaluating biomarkers of disease activity, (4) understanding metabolic dysregulation across the spectrum of pulmonary hypertension, and (5) advancing knowledge in chronic thromboembolic pulmonary hypertension. Focusing on these five thematic contexts we review the current state of knowledge, summarize presented research abstracts, appraise their significance and limitations, and then discuss relevant future directions in pulmonary hypertension clinical research.

scholarly journals Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 499
Author(s):  
Kalpana D. Acharya ◽  
Hye L. Noh ◽  
Madeline E. Graham ◽  
Sujin Suk ◽  
Randall H. Friedline ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Glucose Turnover ◽  
Female Mice ◽  
Adult Mice ◽  
Diet Induced Obesity ◽  
Metabolic Dysregulation ◽  
Regulation Of Metabolism ◽  
Junction Protein

A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.

scholarly journals Role of FXR in Bile Acid and Metabolic Homeostasis in NASH: Pathogenetic Concepts and Therapeutic Opportunities

2021 ◽  
Author(s):  
Richard Radun ◽  
Michael Trauner
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Enterohepatic Circulation ◽  
Therapeutic Potential ◽  
Farnesoid X Receptor ◽  
Metabolic Homeostasis ◽  
Nonalcoholic Fatty Liver ◽  
Metabolic Dysregulation ◽  
Attractive Therapeutic Target

AbstractNonalcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease, increasingly contributing to the burden of liver transplantation. In search for effective treatments, novel strategies addressing metabolic dysregulation, inflammation, and fibrosis are continuously emerging. Disturbed bile acid (BA) homeostasis and microcholestasis via hepatocellular retention of potentially toxic BAs may be an underappreciated factor in the pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) as its progressive variant. In addition to their detergent properties, BAs act as signaling molecules regulating cellular homeostasis through interaction with BA receptors such as the Farnesoid X receptor (FXR). Apart from being a key regulator of BA metabolism and enterohepatic circulation, FXR regulates metabolic homeostasis and has immune-modulatory effects, making it an attractive therapeutic target in NAFLD/NASH. In this review, the molecular basis and therapeutic potential of targeting FXR with a specific focus on restoring BA and metabolic homeostasis in NASH is summarized.

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