Fatty acid–induced NLRP3-ASC inflammasome activation interferes with insulin signaling

Nature Immunology, Journal Year: 2011, Volume and Issue: 12(5), P. 408 - 415

Published: April 10, 2011

Language: Английский

---

Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2010, Volume and Issue: 1813(7), P. 1269 - 1278

Published: Oct. 7, 2010

Language: Английский

---

Metformin, Independent of AMPK, Inhibits mTORC1 in a Rag GTPase-Dependent Manner

Cell Metabolism, Journal Year: 2010, Volume and Issue: 11(5), P. 390 - 401

Published: May 1, 2010

Language: Английский

---

AMPK and SIRT1: a long-standing partnership?

AJP Endocrinology and Metabolism, Journal Year: 2010, Volume and Issue: 298(4), P. E751 - E760

Published: Jan. 27, 2010

AMP-activated protein kinase (AMPK) and the histone/protein deacetylase SIRT1 are fuel-sensing molecules that have coexisted in cells throughout evolution. When a cell's energy state is diminished, AMPK activation restores balance by stimulating catabolic processes generate ATP downregulating anabolic consume but not acutely needed for survival. turn best known historically producing genetic changes mediate increase longevity caused calorie restriction. Although two been studied intensively many years, only recently has it become apparent they similar effects on diverse such as cellular fuel metabolism, inflammation, mitochondrial function. In this review we will examine evidence these similarities occur because both regulate each other share common target molecules. addition, discuss clinical relevance of interactions particular possibility their dysregulation predisposes to disorders type 2 diabetes atherosclerotic cardiovascular disease therapy.

Language: Английский

---

AMPK, insulin resistance, and the metabolic syndrome

Journal of Clinical Investigation, Journal Year: 2013, Volume and Issue: 123(7), P. 2764 - 2772

Published: June 30, 2013

Insulin resistance (IR) and hyperinsulinemia are hallmarks of the metabolic syndrome, as central adiposity, dyslipidemia, a predisposition to type 2 diabetes, atherosclerotic cardiovascular disease, hypertension, certain cancers. Regular exercise calorie restriction have long been known increase insulin sensitivity decrease prevalence these disorders. The subsequent identification AMP-activated protein kinase (AMPK) its activation by fuel deprivation led studies effects AMPK on both IR syndrome–related diseases. In this review, we evaluate body literature, with special emphasis hypothesis that dysregulation is pathogenic factor for disorders in humans target their prevention therapy.

Language: Английский

---

AMPK and mTOR in Cellular Energy Homeostasis and Drug Targets

The Annual Review of Pharmacology and Toxicology, Journal Year: 2011, Volume and Issue: 52(1), P. 381 - 400

Published: March 3, 2011

The mammalian target of rapamycin (mTOR) is a central controller cell growth and proliferation. mTOR forms two distinct complexes, complex 1 (mTORC1) 2 (mTORC2). mTORC1 regulated by multiple signals such as factors, amino acids, cellular energy regulates numerous essential processes including translation, transcription, autophagy. AMP-activated protein kinase (AMPK) sensor signal transducer that wide array metabolic stresses. These pathways serve signaling nexus for regulating metabolism, homeostasis, growth, dysregulation each pathway may contribute to the development disorders obesity, type diabetes, cancer. This review focuses on our current understanding relationship between AMPK discusses their roles in organismal homeostasis.

Language: Английский

---

AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan

Journal of Molecular Medicine, Journal Year: 2011, Volume and Issue: 89(7), P. 667 - 676

Published: March 22, 2011

Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of energy metabolic homeostasis and thus major survival factor in variety stresses also the aging process. Metabolic syndrome associated with low-grade, chronic inflammation, primarily adipose tissue. A low-level inflammation present There are emerging results indicating that AMPK signaling can inhibit inflammatory responses induced by nuclear factor-κB (NF-κB) system. The NF-κB subunits not direct phosphorylation targets AMPK, but inhibition mediated several downstream e.g., SIRT1, PGC-1α, p53, Forkhead box O (FoxO) factors. seems to enhance metabolism while it repress linked stress, nutritional overload during endoplasmic reticulum oxidative which involved disorders Interestingly, many target proteins so-called longevity factors, FoxOs, only increase stress resistance extend lifespan organisms responses. activation capacity declines could augment diseases accelerate We will review pathways suppression inflammation. emphasize have significant impact on both healthspan lifespan.

Language: Английский

---

AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network

Ageing Research Reviews, Journal Year: 2011, Volume and Issue: 11(2), P. 230 - 241

Published: Dec. 16, 2011

Efficient control of energy metabolic homeostasis, enhanced stress resistance, and qualified cellular housekeeping are the hallmarks improved healthspan extended lifespan. AMPK signaling is involved in regulation all these characteristics via an integrated network. Many studies with lower organisms have revealed that increased activity can extend Experiments mammals demonstrated controls autophagy through mTOR ULK1 which augment quality housekeeping. Moreover, AMPK-induced stimulation FoxO/DAF-16, Nrf2/SKN-1, SIRT1 pathways improves resistance. Furthermore, inhibition NF-κB by suppresses inflammatory responses. Emerging indicate responsiveness clearly declines aging. The loss sensitivity activation to impairs regulation, increases oxidative reduces autophagic clearance. These age-related changes activate innate immunity defence, triggering a low-grade inflammation disorders. We will review detail this network metabolism, degradation resistance ultimately aging process.

Language: Английский

---

The Ancient Drug Salicylate Directly Activates AMP-Activated Protein Kinase

Science, Journal Year: 2012, Volume and Issue: 336(6083), P. 918 - 922

Published: April 21, 2012

Salicylate, a plant product, has been in medicinal use since ancient times. More recently, it replaced by synthetic derivatives such as aspirin and salsalate, both of which are rapidly broken down to salicylate vivo. At concentrations reached plasma after administration salsalate or at high doses, activates adenosine monophosphate-activated protein kinase (AMPK), central regulator cell growth metabolism. Salicylate binds the same site activator A-769662 cause allosteric activation inhibition dephosphorylation activating phosphorylation site, threonine-172. In AMPK knockout mice, effects increase fat utilization lower fatty acids vivo were lost. Our results suggest that could explain some beneficial humans.

Language: Английский

---

AMPK signalling in health and disease

Current Opinion in Cell Biology, Journal Year: 2017, Volume and Issue: 45, P. 31 - 37

Published: Feb. 21, 2017

Language: Английский

---