Liver-Specific Activation of AMPK Prevents Steatosis on a High-Fructose Diet DOI Creative Commons
Angela Woods,

Jennet Williams,

Phillip Muckett

et al.

Cell Reports, Journal Year: 2017, Volume and Issue: 18(13), P. 3043 - 3051

Published: March 1, 2017

AMP-activated protein kinase (AMPK) plays a key role in integrating metabolic pathways response to energy demand. We identified mutation the γ1 subunit (γ1D316A) that leads activation of AMPK. generated mice with this study effect chronic liver-specific AMPK vivo. Primary hepatocytes isolated from these have reduced gluconeogenesis and fatty acid synthesis, but there is no on oxidation compared cells wild-type mice. Liver-specific decreases lipogenesis vivo completely protects against hepatic steatosis when are fed high-fructose diet. Our findings demonstrate sufficient protect triglyceride accumulation, hallmark non-alcoholic liver disease (NAFLD). These results emphasize clinical relevance activating combat NAFLD potentially other associated complications (e.g., cirrhosis hepatocellular carcinoma).

Language: Английский

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

et al.

Nature Reviews Neurology, Journal Year: 2018, Volume and Issue: 14(3), P. 168 - 181

Published: Jan. 29, 2018

Language: Английский

Citations

1182
The liver DOI Creative Commons
Elijah Trefts, Maureen Gannon, David H. Wasserman

et al.

Current Biology, Journal Year: 2017, Volume and Issue: 27(21), P. R1147 - R1151

Published: Nov. 1, 2017

Language: Английский

Citations

1043
Cardiovascular and Metabolic Heterogeneity of Obesity DOI Open Access
Ian J. Neeland, Paul Poirier, Jean–Pierre Després

et al.

Circulation, Journal Year: 2018, Volume and Issue: 137(13), P. 1391 - 1406

Published: March 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.

Language: Английский

Citations

630
Transcriptional regulation of hepatic lipogenesis DOI
Yuhui Wang, José A. Viscarra, Sun-Joong Kim

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2015, Volume and Issue: 16(11), P. 678 - 689

Published: Oct. 22, 2015

Language: Английский

Citations

588
Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinoma DOI Creative Commons
Ankur Sharma, Justine Jia Wen Seow, Charles‐Antoine Dutertre

et al.

Cell, Journal Year: 2020, Volume and Issue: 183(2), P. 377 - 394.e21

Published: Sept. 24, 2020

Language: Английский

Citations

502
PGC-1α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism DOI Creative Commons
Sergio Rius‐Pérez, Isabel Torres-Cuevas, Iván Millán

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 20

Published: March 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.

Language: Английский

Citations

468
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, Journal Year: 2020, Volume and Issue: 472(9), P. 1273 - 1298

Published: June 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.

Language: Английский

Citations

384
New insights into the pathophysiology of dyslipidemia in type 2 diabetes DOI
Marja‐Riitta Taskinen, Jan Borén

Atherosclerosis, Journal Year: 2015, Volume and Issue: 239(2), P. 483 - 495

Published: Feb. 7, 2015

Language: Английский

Citations

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

Raymond Vanholder,

Ziad A. Massy

et al.

Nature Reviews Nephrology, Journal Year: 2017, Volume and Issue: 13(6), P. 344 - 358

Published: April 24, 2017

Language: Английский

Citations

353
PGC-1α as a Pivotal Factor in Lipid and Metabolic Regulation DOI Open Access
Ching‐Feng Cheng, Hui‐Chen Ku, Heng Lin

et al.

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 19(11), P. 3447 - 3447

Published: Nov. 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.

Language: Английский

Citations

347