Cellular energy sensors: AMPK and beyond

López, Miguel; Diéguez, Carlos

doi:10.1016/j.mce.2014.11.007

Cited by 4 publications

(3 citation statements)

References 48 publications

(80 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4A ). AMPK is a known nutrient and energy sensor that maintains cellular energy homeostasis when the ratios of intracellular AMP/ATP levels are increased ( 40 , 41 ). AMPK is activated by phosphorylation at Thr172 (p-AMPK) ( 42 ).…”

Section: Resultsmentioning

confidence: 99%

Dual targets of lethal apoptosis and protective autophagy in liver cancer with periplocymarin elicit a limited therapeutic effect

et al. 2023

View full text Add to dashboard Cite

Cardiac glycosides (CGs) are candidate anticancer agents that function by increasing [Ca 2+ ]i to induce apoptotic cell death in several types of cancer cells. However, new findings have shown that the anti-cancer effects of CGs involve complex cell-signal transduction mechanisms. Hence, exploring the potential mechanisms of action of CGs may provide insight into their anti-cancer effects and thus aid in the selection of the appropriate CG. Periplocymarin (PPM), which is a cardiac glycoside, is an active ingredient extracted from Cortex periplocae. The role of PPM was evaluated in HepG2 cells and xenografted nude mice. Cell proliferation, real-time ATP rate assays, western blotting, cell apoptosis assays, short interfering RNA transfection, the patch clamp technique, electron microscopy, JC-1 staining, immunofluorescence staining and autophagic flux assays were performed to evaluate the function and regulatory mechanisms of PPM in vitro . The in vivo activity of the PPM was assessed using a mouse xenograft model. The present study demonstrated that PPM synchronously activated lethal apoptosis and protective autophagy in liver cancer, and the initiation of autophagy counteracted the inherent pro-apoptotic capacity and impaired the anti-cancer effects. Specifically, PPM exerted a proapoptotic effect in HepG2 cells and activated macroautophagy by initiation of the AMPK/ULK1 and mTOR signaling pathways. Activation of macroautophagy counteracted the pro-apoptotic effects of PPM, but when it was combined with an autophagy inhibitor, the anti-cancer effects of PPM in mice bearing HepG2 xenografts were observed. Collectively, these results indicated that a self-limiting effect impaired the pro-apoptotic effects of PPM in liver cancer, but when combined with an autophagy inhibitor, it may serve as a novel therapeutic option for the management of liver cancer.

show abstract

Section: Resultsmentioning

confidence: 99%

Dual targets of lethal apoptosis and protective autophagy in liver cancer with periplocymarin elicit a limited therapeutic effect

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Hence, the reduced expression of Cd36 in LR ⌬InsR mice may subsidize the reduced circulating levels of basal glucose. Likewise, the AMP-activated protein kinase (AMPK) enzyme, a cellular energy sensor that regulates glucose and fat metabolism in response to change in cellular energy charge (13,32), may also contribute to the higher fat mass. Recent reports have suggested that AMPK modulates lipid synthesis, lipolysis, and fatty acid oxidation through phosphorylation of key substrates (51).…”

Section: Discussionmentioning

confidence: 99%

Insulin signaling in LepR cells modulates fat and glucose homeostasis independent of leptin

Borges

Han

Allen

et al. 2019

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Hypothalamic neurons detect changes in circulating hormones such as leptin and insulin and put forward outputs to sustain energy and glucose homeostasis. Because leptin and insulin receptors colocalize in ~40–60% of neurons in the hypothalamus, we characterized the metabolic phenotype of mice with selective deletion of the insulin receptor (InsR) in LepR cells. LRΔInsR mice presented no difference in body weight and insulin levels but increased fat mass. In the light phase, LRΔInsR mice exhibited increased food intake, locomotor activity, carbon dioxide production, and respiratory exchange rate. These mice showed reduced fat oxidation and reduced expression of cluster of differentiation 36 and AMP-activated protein kinase-α1 in the liver, increased glucose oxidation in the light phase, and overall reduced basal glucose levels. To verify the impact of InsR deletion in LepR cells in obesity, we generated ob/ ob InsRfl, ob/ ob LRcre, and ob/ ob LRΔInsR mice. The ob/ ob LRΔInsR mice had higher body weight, fat mass, and expression of genes related to fat metabolism in the liver. No difference in food intake despite increased neuropeptide Y and agouti-related peptide expression, and no difference in energy expenditure, fat, or glucose oxidation was found in ob/ ob LRΔInsR compared with LRcre or LRΔInsR controls. Remarkably, basal glucose levels were reduced, and the expression of genes associated with glucose metabolism in the liver was higher. Insulin signaling in LepR cells is required for the proper fat and glucose oxidation. These effects are independent of leptin given that the leptin-deficient ob/ ob LRΔInsR mice also presented reduced glycemia and higher adiposity. The mechanisms underlying these responses remain to be unveiled.

show abstract

“…AMPK is a well-known kinase (Beg et al 1973;Carling et al 1989;Carling et al 1987;Carlson and Kim 1973;Ferrer et al 1985;Ingebritsen et al 1978;Munday et al 1988;Yeh and Kim 1980) with important physiological and pathological roles (Hardie 2014;Hardie et al 2016;Herzig and Shaw 2018;Lopez and Dieguez 2014). The α, β and γ subunits of AMPK form a heterotrimeric complex (Davies et al 1994;Michell et al 1996;Mitchelhill et al 1994).…”

Section: Introductionmentioning

confidence: 99%

LKB1 Is Physiologically Required for Sleep from Drosophila to the Mouse

Liu

Jiang

et al. 2021

Preprint

View full text Add to dashboard Cite

LKB1 is known as a master kinase for 14 kinases related to the adenosine monophosphate (AMP)-activated protein kinase (AMPK). Two of them (SIK3 and AMPKa;) have previously been implicated in sleep regulation. We generated loss-of-function (LOF) mutants for Lkb1 in both Drosophila and mice. Sleep was reduced in Lkb1-mutant flies and in flies with neuronal deletion of Lkb1. Sleep was reduced in mice after virally mediated reduction of Lkb1 in the brain. Electroencephalography (EEG) analysis showed that non-rapid eye movement (NREM) sleep and sleep need were both reduced in Lkb1-mutant mice. These results indicate that LKB1 plays a physiological role in sleep regulation conserved from flies to mice.

show abstract

Cellular energy sensors: AMPK and beyond

Cited by 4 publications

References 48 publications

Dual targets of lethal apoptosis and protective autophagy in liver cancer with periplocymarin elicit a limited therapeutic effect

Dual targets of lethal apoptosis and protective autophagy in liver cancer with periplocymarin elicit a limited therapeutic effect

Insulin signaling in LepR cells modulates fat and glucose homeostasis independent of leptin

LKB1 Is Physiologically Required for Sleep from Drosophila to the Mouse

Contact Info

Product

Resources

About