Association of Altered Liver Enzymes With Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers DOI Creative Commons
Kwangsik Nho, Alexandra Kueider‐Paisley, Shahzad Ahmad

и другие.

JAMA Network Open, Год журнала: 2019, Номер 2(7), С. e197978 - e197978

Опубликована: Июль 31, 2019

Importance

Increasing evidence suggests an important role of liver function in the pathophysiology Alzheimer disease (AD). The is a major metabolic hub; therefore, investigating association with AD, cognition, neuroimaging, and CSF biomarkers would improve understanding dysfunction AD.

Objective

To examine whether markers are associated cognitive "A/T/N" (amyloid, tau, neurodegeneration) for

Design, Setting, Participants

In this cohort study, serum-based were measured from September 1, 2005, to August 31, 2013, 1581 AD Neuroimaging Initiative participants along measures, cerebrospinal fluid (CSF) biomarkers, brain atrophy, glucose metabolism, amyloid-β accumulation. Associations AD-associated clinical A/T/N assessed using generalized linear models adjusted confounding variables multiple comparisons. Statistical analysis was performed November 2017, February 28, 2019.

Exposures

Five (total bilirubin, albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase) used as exposure variables.

Main Outcomes Measures

Primary outcomes included diagnosis composite scores executive functioning memory, atrophy by magnetic resonance imaging, metabolism fludeoxyglucose F 18 (18F) positron emission tomography, accumulation [18F]florbetapir tomography.

Results

Participants (n = 1581; 697 women 884 men; mean [SD] age, 73.4 [7.2] years) 407 cognitively normal older adults, 20 significant memory concern, 298 early mild impairment, 544 late 312 An elevated aminotransferase (AST) (ALT) ratio lower levels ALT (AST ratio: odds ratio, 7.932 [95% CI, 1.673-37.617];P .03; ALT: 0.133 0.042-0.422];P .004) poor performance β [SE], −0.465 [0.180];P .02 score; −0.679 [0.215];P .006 0.397 [0.128];P 0.637 [0.152];P < .001 score). Increased AST values 1-42 (β −0.170 [0.061];P .04) increased deposition (amyloid biomarkers), higher phosphorylated tau181(β 0.175 [0.055];P .02) (tau biomarkers) total tau 0.160 [0.049];P reduced −0.123 [0.042];P .03) (neurodegeneration biomarkers). Lower 0.096 [0.030];P greater

Conclusions Relevance

Consistent associations highlight involvement disturbances Further studies needed determine if these represent causative or secondary role. Liver enzyme opens avenues novel diagnostics therapeutics.

Язык: Английский

Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums DOI
Steven E. Arnold, Zoe Arvanitakis, Shannon L. Macauley

и другие.

Nature Reviews Neurology, Год журнала: 2018, Номер 14(3), С. 168 - 181

Опубликована: Янв. 29, 2018

Язык: Английский

Процитировано

1212
The liver DOI Creative Commons
Elijah Trefts, Maureen Gannon, David H. Wasserman

и другие.

Current Biology, Год журнала: 2017, Номер 27(21), С. R1147 - R1151

Опубликована: Ноя. 1, 2017

Язык: Английский

Процитировано

1081
Cardiovascular and Metabolic Heterogeneity of Obesity DOI Open Access
Ian J. Neeland, Paul Poirier, Jean‐Pierre Després

и другие.

Circulation, Год журнала: 2018, Номер 137(13), С. 1391 - 1406

Опубликована: Март 26, 2018

The prevalence of obesity has increased globally over the last 2 decades. Although body mass index been a convenient and simple at population level, studies have shown that defined by alone is remarkably heterogeneous condition with varying cardiovascular metabolic manifestations across individuals. Adipose tissue an exquisitely active organ engaged in cross-talk between various systems; perturbation adipose results pathological response to positive caloric balance susceptible individuals directly indirectly contributes disease. Inadequate subcutaneous expansion face dietary triglycerides leads visceral ectopic fat deposition, inflammatory/adipokine dysregulation, insulin resistance. Conversely, preferential storage lower depot may act as buffer protect other tissues from lipotoxicity caused lipid overflow fat. Translational, epidemiological, clinical past 30 years clearly demonstrated strong link development syndrome characterized atherogenic dyslipidemia, hyperinsulinemia/glucose intolerance, hypertension, atherosclerosis, adverse cardiac remodeling/heart failure. This relationship even more nuanced when entities such metabolically healthy phenotype paradox are considered. it clear accumulation visceral/ectopic major contributor risk above beyond index, implementation distribution assessment into practice remains challenge. Anthropometric indexes easily implemented, but newer imaging-based methods offer improved sensitivity specificity for measuring specific depots. Lifestyle, pharmacological, surgical interventions allow multidisciplinary approach overweight/obesity improve outcomes align public health message combat growing epidemic worldwide build healthier lives free diseases.

Язык: Английский

Процитировано

639
Transcriptional regulation of hepatic lipogenesis DOI
Yuhui Wang, José A. Viscarra, Sun-Joong Kim

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2015, Номер 16(11), С. 678 - 689

Опубликована: Окт. 22, 2015

Язык: Английский

Процитировано

590
Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinoma DOI Creative Commons
Ankur Sharma, Justine Jia Wen Seow, Charles‐Antoine Dutertre

и другие.

Cell, Год журнала: 2020, Номер 183(2), С. 377 - 394.e21

Опубликована: Сен. 24, 2020

Язык: Английский

Процитировано

509
PGC-1α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism DOI Creative Commons
Sergio Rius‐Pérez, Isabel Torres-Cuevas, Iván Millán

и другие.

Oxidative Medicine and Cellular Longevity, Год журнала: 2020, Номер 2020, С. 1 - 20

Опубликована: Март 9, 2020

Peroxisome proliferator-activated receptor- γ coactivator (PGC)-1 α is a transcriptional described as master regulator of mitochondrial biogenesis and function, including oxidative phosphorylation reactive oxygen species detoxification. PGC-1 highly expressed in tissues with high energy demands, it clearly associated the pathogenesis metabolic syndrome its principal complications obesity, type 2 diabetes mellitus, cardiovascular disease, hepatic steatosis. We herein review molecular pathways regulated by , which connect stress metabolism inflammatory response syndrome. regulates expression antioxidant genes, manganese superoxide dismutase, catalase, peroxiredoxin 3 5, uncoupling protein 2, thioredoxin reductase thus prevents injury dysfunction. Dysregulation alters redox homeostasis cells exacerbates response, commonly accompanied disturbances. During inflammation, low levels downregulate gene expression, induce stress, promote nuclear factor kappa B activation. In syndrome, characterized chronic grade dysregulation modifies properties altering function promoting accumulation. conclusion, acts an essential node connecting regulation, control, pathways, interesting therapeutic target that may have significant benefits for number diseases.

Язык: Английский

Процитировано

477
Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease DOI Creative Commons
Alexandra Chadt, Hadi Al‐Hasani

Pflügers Archiv - European Journal of Physiology, Год журнала: 2020, Номер 472(9), С. 1273 - 1298

Опубликована: Июнь 26, 2020

Abstract A family of facilitative glucose transporters (GLUTs) is involved in regulating tissue-specific uptake and metabolism the liver, skeletal muscle, adipose tissue to ensure homeostatic control blood levels. Reduced transport activity results aberrant use energy substrates associated with insulin resistance type 2 diabetes. It well established that GLUT2, main regulator hepatic hexose flux, GLUT4, workhorse insulin- contraction-stimulated are critical contributors whole-body glycemia. However, molecular mechanism how controls across membranes its relation impaired glycemic diabetes remains not sufficiently understood. An array circulating metabolites hormone-like molecules potential supplementary play roles fine-tuning flux between different organs response an altered demand.

Язык: Английский

Процитировано

390
New insights into the pathophysiology of dyslipidemia in type 2 diabetes DOI
Marja‐Riitta Taskinen, Jan Borén

Atherosclerosis, Год журнала: 2015, Номер 239(2), С. 483 - 495

Опубликована: Фев. 7, 2015

Язык: Английский

Процитировано

373
The systemic nature of CKD DOI Open Access
Carmine Zoccali,

Raymond Vanholder,

Ziad A. Massy

и другие.

Nature Reviews Nephrology, Год журнала: 2017, Номер 13(6), С. 344 - 358

Опубликована: Апрель 24, 2017

Язык: Английский

Процитировано

360
PGC-1α as a Pivotal Factor in Lipid and Metabolic Regulation DOI Open Access
Ching‐Feng Cheng, Hui‐Chen Ku, Heng Lin

и другие.

International Journal of Molecular Sciences, Год журнала: 2018, Номер 19(11), С. 3447 - 3447

Опубликована: Ноя. 2, 2018

Traditionally, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a 91 kDa transcription factor, regulates lipid metabolism and long-chain fatty acid oxidation by upregulating the expression of several genes tricarboxylic cycle mitochondrial pathway. In addition, PGC-1α to control mitochondria DNA replication cellular oxidative metabolism. Recently, new insights showed that myokines such as irisin myostatin are epigenetically regulated in skeletal muscles, thereby modulating systemic energy balance, with marked expansion volume density capacity healthy or diseased myocardia. our studies evaluating whether overexpression epicardial adipose tissue can act paracrine organ improve repair cardiac function, we found hepatic increased decreased triacylglycerol storage secretion vivo vitro. this review, discuss recent showing may regulate fusion⁻fission homeostasis affect renal function acute chronic kidney injury. Furthermore, is an emerging protein biphasic role cancer, acting both tumor suppressor promoter thus representing unresolved topic for cancer biology studies. summary, review paper demonstrates plays central coordinating gene key components biogenesis critical metabolic regulator many vital organs, including white brown tissue, muscle, heart, liver, kidney.

Язык: Английский

Процитировано

355