Protective effects of gomisin N against hepatic steatosis through AMPK activation

AMP-activated protein kinase (AMPK) is known as a pivotal cellular energy sensor, mediating the adaptation to low energy levels by deactivating anabolic processes and activating catabolic processes in order to restore the cellular ATP supply when the cellular AMP/ATP ratio is increased. Besides this well-known role, it has also been shown to exert protective effects under hypoxia. While an insufficient supply with oxygen might easily deplete cellular energy levels, i.e., ATP concentration, manifold other mechanisms have been suggested and are heavily disputed regarding the activation of AMPK under hypoxia independently from cellular AMP concentrations. However, an activation of AMPK preceding energy depletion could induce a timely adaptation reaction preventing more serious damage. A connection between AMPK and the master regulator of hypoxic adaptation via gene transcription, hypoxia-inducible factor (HIF), has also been taken into account, orchestrating their concerted protective action. This review will summarize the current knowledge on mechanisms of AMPK activation under hypoxia and its interrelationship with HIF.

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Crocin Improves Insulin Sensitivity and Ameliorates Adiposity by Regulating AMPK-CDK5-PPARγ Signaling

BioMed Research International ◽

10.1155/2020/9136282 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Kai Fang ◽

Ming Gu

Keyword(s):

Protein Level ◽

Biological Activities ◽

Protective Effects ◽

Metabolic Dysfunction ◽

Ampk Activation ◽

Diabetic Mice ◽

Wild Type ◽

Ampk Signaling ◽

Beneficial Effects

Crocin is a carotenoid compound which possesses multiple biological activities. Our and other laboratory’s previous findings show that crocin alleviates obesity and type 2 diabetes-related complications. We have found that crocin activates AMP-activated protein kinase (AMPK) signaling and inhibition of AMPK suppresses crocin-induced protective effects. However, the causal role of AMPK activation in the biological role of crocin is still not verified. In the present study, we showed that crocin markedly inhibits the changes of glucose metabolic parameters and serum lipid profiles in wild type diabetic mice. In AMPKα KO diabetic mice, those protective effects of crocin against glucose and lipid metabolic dysfunction were abolished. These results demonstrated AMPK activation was responsible for the beneficial effects of crocin on metabolic dysfunction. Moreover, we have shown that the antiobese effect of crocin has been abolished by the deficiency of AMPKα. We also showed that crocin induced a significant decrease of CDK5 protein level in wild type diabetic mice, while this effect was abolished in AMPKα KO diabetic mice. The regulation of downstream targets of CDK5/PPARγ by crocin was abolished by the deficiency of AMPK. In conclusion, our study verified that activation of AMPK is involved in crocin-induced protective effects against glucose and lipid metabolic dysfunction. Activation of AMPK downregulates the protein level of CDK5, followed by the decrease of PPARγ phosphorylation, leading to the inhibition of adipose formation and metabolic dysfunction. Our study provides new insights into the mechanism of protective effects of crocin and interaction of AMPK and CDK5/PPARγ signaling.

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Adiponectin Facilitates Postconditioning Cardioprotection through Both AMPK-Dependent Nuclear and AMPK-Independent Mitochondrial STAT3 Activation

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/4253457 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17 ◽

Cited By ~ 1

Author(s):

Qiqi Zhu ◽

Haobo Li ◽

Xiang Xie ◽

Xiaozhen Chen ◽

Ramoji Kosuru ◽

...

Keyword(s):

Cell Injury ◽

Biological Effects ◽

Ischemia Reperfusion ◽

Protective Effects ◽

Ampk Activation ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Myocardial Ischemia Reperfusion ◽

Myocardial Injuries ◽

Amp Activated Protein Kinase

Myocardial ischemic postconditioning- (IPo-) mediated cardioprotection against myocardial ischemia-reperfusion (IR) injury needs the activation of signal transducer and activator of transcription 3 (STAT3), which involves adiponectin (APN). APN confers its biological effects through AMP-activated protein kinase- (AMPK-) dependent and AMPK-independent pathways. However, the role of AMPK in APN-mediated STAT3 activation in IPo cardioprotection is unknown. We hypothesized that APN-mediated STAT3 activation in IPo is AMPK-independent and that APN through AMPK-dependent STAT3 activation facilitates IPo cardioprotection. Here, Sprague-Dawley rats were subjected to myocardial IR without or with IPo and/or APN. APN or IPo significantly improved postischemic cardiac function and reduced myocardial injury and oxidative stress, and their combination further attenuated postischemic myocardial injuries. APN or its combination with IPo but not IPo alone significantly increased AMPK activation and both nuclear and mitochondrial STAT3 activation, while IPo significantly enhanced mitochondrial but not nuclear STAT3 activation. In primarily isolated cardiomyocytes, recombined globular APN (gAd), hypoxic postconditioning (HPo), or their combination significantly attenuated hypoxia/reoxygenation-induced cell injury and increased nuclear and/or mitochondrial STAT3 activation. STAT3 inhibition had no impact on gAd or gAd in combination with HPo-induced AMPK activation but abolished their cellular protective effects. AMPK inhibition did not affect HPo cardioprotection but abolished gAd cardioprotection and disabled gAd to facilitate/enhance HPo cardioprotection and STAT3 activation. These results suggest that APN confers cardioprotection through AMPK-dependent and AMPK-independent STAT3 activation, while IPo confers cardioprotection through AMPK-independent mitochondrial STAT3 activation. Joint use of APN and IPo synergistically attenuated myocardial IR injury by activating STAT3 via distinct signaling pathways.

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AMPK activation caused by reduced liver lactate metabolism protects against hepatic steatosis in MCT1 haploinsufficient mice

Molecular Metabolism ◽

10.1016/j.molmet.2017.10.005 ◽

2017 ◽

Vol 6 (12) ◽

pp. 1625-1633 ◽

Cited By ~ 12

Author(s):

Lionel Carneiro ◽

Mohamed Asrih ◽

Cendrine Repond ◽

Christine Sempoux ◽

Jean-Christophe Stehle ◽

...

Keyword(s):

Hepatic Steatosis ◽

Ampk Activation ◽

Lactate Metabolism

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Fish oil supplementation inhibits endoplasmic reticulum stress and improves insulin resistance: involvement of AMP-activated protein kinase

Food & Function ◽

10.1039/c6fo01841f ◽

2017 ◽

Vol 8 (4) ◽

pp. 1481-1493 ◽

Cited By ~ 20

Author(s):

Wenqi Yang ◽

Xu Chen ◽

Ming Chen ◽

Yanping Li ◽

Qing Li ◽

...

Keyword(s):

Insulin Resistance ◽

Endoplasmic Reticulum ◽

Protein Kinase ◽

Endoplasmic Reticulum Stress ◽

Fish Oil ◽

Er Stress ◽

Protective Effects ◽

Ampk Activation ◽

Amp Activated Protein Kinase ◽

Fish Oil Supplementation

ER stress inhibition through AMPK activation may explain the protective effects of fish oil against HFD-induced insulin resistance.

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The Protective Effects ofAreca catechuExtract on Cognition and Social Interaction Deficits in a Cuprizone-Induced Demyelination Model

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/426092 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 9

Author(s):

Abulimiti Adilijiang ◽

Teng Guan ◽

Jue He ◽

Kelly Hartle ◽

Wenqiang Wang ◽

...

Keyword(s):

Cognitive Ability ◽

Social Activity ◽

Precursor Cell ◽

Protective Effects ◽

Ampk Activation ◽

Oligodendrocyte Precursor Cell ◽

Ampk Signaling ◽

Areca Catechu ◽

Oligodendrocyte Precursor ◽

Myelin Damage

Schizophrenia is a serious psychiatric illness with an unclear cause. One theory is that demyelination of white matter is one of the main pathological factors involved in the development of schizophrenia. The current study evaluated the protective effects ofAreca catechunut extract (ANE) on a cuprizone-induced demyelination mouse model. Two doses of ANE (1% and 2%) were administered orally in the diet for 8 weeks. Animals subjected to demyelination showed impaired spatial memory and less social activity. In addition, mice subjected to demyelination displayed significant myelin damage in cortex and demonstrated a higher expression of NG2 and PDGFRαand AMPK activation. ANE treatment not only significantly enhanced cognitive ability and social activity, but also protected myelin against cuprizone toxicity by promoting oligodendrocyte precursor cell (OPC) differentiation. In addition, ANE treatment demonstrated significant dephosphorylation of AMPKα, indicating a regulatory role for ANE in schizophrenia. This study showed that ANE treatment may enhance cognitive ability and social activity by facilitating OPC differentiation and protecting against myelin damage in cortex. Results also suggest the AMPK signaling pathway may be involved in this process.

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Beneficial Metabolic Effects of TREM2 in Obesity are Uncoupled from its Expression on Macrophages

10.2337/figshare.14074550.v1 ◽

2021 ◽

Author(s):

Omar Sharif ◽

Julia Stefanie Brunner ◽

Ana Korosec ◽

Rui Martins ◽

Alexander Jais ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Hepatic Steatosis ◽

Immune Cell ◽

Metabolic Effects ◽

Sphingolipid Metabolism ◽

Protective Effects ◽

Tissue Macrophage ◽

Insulin Tolerance ◽

Ceramide Synthesis

Obesity-induced white adipose tissue (WAT) hypertrophy is associated with elevated adipose tissue macrophage (ATM) content. Overexpression of the triggering receptor expressed on myeloid cells 2 (TREM2) reportedly increases adiposity, worsening health. Paradoxically, using insulin resistance, elevated fat mass and hypercholesterolemia as hallmarks of unhealthy obesity, a recent report demonstrated ATM-expressed TREM2 promoted health. Here, we identified that in mice TREM2 deficiency aggravated diet-induced insulin resistance and hepatic steatosis independently of fat and cholesterol levels. Metabolomics linked TREM2 deficiency with elevated obesity-instigated serum ceramides that correlated with impaired insulin sensitivity. Remarkably, while inhibiting ceramide synthesis exerted no influences on TREM2-dependent ATM remodeling, inflammation or lipid load, it restored insulin tolerance, reversing adipose hypertrophy and secondary hepatic steatosis of TREM2-deficient animals. Bone marrow transplantation experiments revealed unremarkable influences of immune cell-expressed TREM2 on health instead demonstrating that WAT-intrinsic mechanisms impinging on sphingolipid metabolism dominate in TREM2’s systemic protective effects on metabolic health.

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