The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity

Obesity is becoming a pandemic, and its prevalence is still increasing. Considering that obesity increases the risk of developing cardiometabolic diseases, research efforts are focusing on new ways to combat obesity. Brown adipose tissue (BAT) has emerged as a possible target to achieve this for its functional role in energy expenditure by means of increasing thermogenesis. An important metabolic sensor and regulator of whole-body energy balance is AMP-activated protein kinase (AMPK), and its role in energy metabolism is evident. This review highlights the mechanisms of BAT activation and investigates how AMPK can be used as a target for BAT activation. We review compounds and other factors that are able to activate AMPK and further discuss the therapeutic use of AMPK in BAT activation. Extensive research shows that AMPK can be activated by a number of different kinases, such as LKB1, CaMKK, but also small molecules, hormones, and metabolic stresses. AMPK is able to activate BAT by inducing adipogenesis, maintaining mitochondrial homeostasis and inducing browning in white adipose tissue. We conclude that, despite encouraging results, many uncertainties should be clarified before AMPK can be posed as a target for anti-obesity treatment via BAT activation.

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Omics multi-layers networks and identification of genes involved in fat storage and metabolism in poultry using interactomics approach

10.21203/rs.3.rs-30697/v1 ◽

2020 ◽

Author(s):

abolfazl bahrami ◽

Farzad Ghafouri ◽

Mostafa Sadeghi ◽

Seyed Reza Miraei-Ashtiani

Keyword(s):

Adipose Tissue ◽

Signaling Pathway ◽

High Throughput Screening ◽

Broiler Chickens ◽

Unsaturated Fatty Acids ◽

Holistic Approach ◽

High Rate ◽

Literature Mining ◽

Ampk Signaling ◽

Ppar Signaling

Abstract Background Fatty acid metabolism in animals has a major impact on production and disease resistance traits. According to the high rate of interactions between lipid metabolism and its regulating properties, a holistic approach is necessary. Methods To study multi-omics layers of adipose tissue and identification of genes involved in fat metabolism, storage and endocrine signaling pathways in two groups of broiler chickens with high and low abdominal fat, high-throughput screening (HTS) techniques were used. The Gene-miRNA interacting bipartite and metabolic-signaling networks were reconstructed using their interactions. Results In the analysis of microarray and RNA-Seq data, 1835 genes were detected by comparing the identified genes with significant expression differences. Then, by comparing, 34 genes and 19 miRNAs were detected as common and main nodes. The literature mining approach was used and 7 genes were identified and added to the common gene set. Module finding revealed three important and functional modules. The detected modules 1, 2, and 3 were involved in the PPAR signaling pathway, biosynthesis of unsaturated fatty acids, and Alzheimer's disease metabolic pathway, adipocytokine, insulin, PI3K-Akt, mTOR and AMPK signaling pathway. Conclusions This approach revealed a new insight for a better understanding of the biological processes associated with adipose tissue.

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Drosophila PDGF/VEGF signaling from muscles to hepatocyte-like cells protects against obesity

eLife ◽

10.7554/elife.56969 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Arpan C Ghosh ◽

Sudhir Gopal Tattikota ◽

Yifang Liu ◽

Aram Comjean ◽

Yanhui Hu ◽

...

Keyword(s):

Adipose Tissue ◽

Lipid Level ◽

Lipid Synthesis ◽

Tissue Lipid ◽

Tor Signaling ◽

Specific Expression ◽

Signaling Axis ◽

Organ Specific ◽

Lipid Stores ◽

Multicellular Organisms

PDGF/VEGF ligands regulate a plethora of biological processes in multicellular organisms via autocrine, paracrine, and endocrine mechanisms. We investigated organ-specific metabolic roles of Drosophila PDGF/VEGF-like factors (Pvfs). We combine genetic approaches and single-nuclei sequencing to demonstrate that muscle-derived Pvf1 signals to the Drosophila hepatocyte-like cells/oenocytes to suppress lipid synthesis by activating the Pi3K/Akt1/TOR signaling cascade in the oenocytes. Functionally, this signaling axis regulates expansion of adipose tissue lipid stores in newly eclosed flies. Flies emerge after pupation with limited adipose tissue lipid stores and lipid level is progressively accumulated via lipid synthesis. We find that adult muscle-specific expression of pvf1 increases rapidly during this stage and that muscle-to-oenocyte Pvf1 signaling inhibits expansion of adipose tissue lipid stores as the process reaches completion. Our findings provide the first evidence in a metazoan of a PDGF/VEGF ligand acting as a myokine that regulates systemic lipid homeostasis by activating TOR in hepatocyte-like cells.

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The sweet side of AMPK signaling: regulation of GFAT1

Biochemical Journal ◽

10.1042/bcj20170006 ◽

2017 ◽

Vol 474 (7) ◽

pp. 1289-1292 ◽

Cited By ~ 3

Author(s):

John W. Scott ◽

Jonathan S. Oakhill

Keyword(s):

Energy Demand ◽

Dynamic Control ◽

Cellular Protein ◽

Post Translational Modification ◽

Nutrient Metabolism ◽

Ampk Signaling ◽

Biochemical Journal ◽

Signaling Axis ◽

Hexosamine Biosynthesis ◽

Living Organisms

Maintaining a steady balance between nutrient supply and energy demand is essential for all living organisms and is achieved through the dynamic control of metabolic processes that produce and consume adenosine-5′-triphosphate (ATP), the universal currency of energy in all cells. A key sensor of cellular energy is the adenosine-5′-monophosphate (AMP)-activated protein kinase (AMPK), which is the core component of a signaling network that regulates energy and nutrient metabolism. AMPK is activated by metabolic stresses that decrease cellular ATP, and functions to restore energy balance by orchestrating a switch in metabolism away from anabolic pathways toward energy-generating catabolic processes. A new study published in a recent issue of Biochemical Journal by Zibrova et al. shows that glutamine:fructose-6-phosphate amidotransferase-1 (GFAT1), the rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), is a physiological substrate of AMPK. The HBP is an offshoot of the glycolytic pathway that drives the synthesis of uridine-5′-diphospho-N-acetylglucosamine, the requisite donor metabolite needed for dynamic β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) of cellular proteins. O-GlcNAcylation is a nutrient-sensitive post-translational modification that, like phosphorylation, regulates numerous intracellular processes. Zibrova et al. show that inhibitory phosphorylation of the GFAT1 residue Ser243 by AMPK in response to physiological or small-molecule activators leads to a reduction in cellular protein O-GlcNAcylation. Further work revealed that AMPK-dependent phosphorylation of GFAT1 promotes angiogenesis in endothelial cells. This elegant study demonstrates that the AMPK–GFAT1 signaling axis serves as an important communication point between two nutrient-sensitive signaling pathways and is likely to play a significant role in controlling physiological processes in many other tissues.

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The ATP-P2X7 Signaling Axis Is Dispensable for Obesity-Associated Inflammasome Activation in Adipose Tissue

Diabetes ◽

10.2337/db11-1389 ◽

2012 ◽

Vol 61 (6) ◽

pp. 1471-1478 ◽

Cited By ~ 46

Author(s):

S. Sun ◽

S. Xia ◽

Y. Ji ◽

S. Kersten ◽

L. Qi

Keyword(s):

Adipose Tissue ◽

Inflammasome Activation ◽

Signaling Axis

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The microbiome-adipose tissue axis in systemic metabolism

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00304.2019 ◽

2020 ◽

Vol 318 (4) ◽

pp. G717-G724 ◽

Cited By ~ 2

Author(s):

Patrick Lundgren ◽

Christoph A. Thaiss

Keyword(s):

Adipose Tissue ◽

Systemic Circulation ◽

Microbial Colonization ◽

Therapeutic Interventions ◽

Intestinal Microbiome ◽

Organ Systems ◽

Host Health ◽

Signaling Axis ◽

Host Metabolism ◽

Gain Access

The intestinal commensal microbiome is an important component of host health, in part by contributing an abundance of metabolites that gain access to the systemic circulation. The microbiome thereby influences the physiology of numerous organ systems outside the gastrointestinal tract. The consequences of this signaling axis between the intestinal microbiome and host are profound, in particular for the modulation of organismal metabolism. Here, we review recent examples whereby the intestinal microbiome influences host metabolism by influencing the biology of adipose tissue. We place a special emphasis on metabolite-driven pathways by which adipose tissue responds to alterations in intestinal microbial colonization. Given its accessibility for therapeutic interventions, the gut microbiome is an attractive relay module for the remote control of systemic metabolism.

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Diet-induced obese rats exhibit impaired LKB1–AMPK signaling in hypothalamus and adipose tissue

Peptides ◽

10.1016/j.peptides.2012.02.003 ◽

2012 ◽

Vol 35 (1) ◽

pp. 23-30 ◽

Cited By ~ 11

Author(s):

Fei-Wang ◽

De-Run Tian ◽

Patrick Tso ◽

Ji-Sheng Han

Keyword(s):

Adipose Tissue ◽

Ampk Signaling ◽

Obese Rats

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Pomegranate vinegar attenuates adiposity in obese rats through coordinated control of AMPK signaling in the liver and adipose tissue

Lipids in Health and Disease ◽

10.1186/1476-511x-12-163 ◽

2013 ◽

Vol 12 (1) ◽

pp. 163 ◽

Cited By ~ 21

Author(s):

Elly Ok ◽

Gyeong-Min Do ◽

Yeni Lim ◽

Ji-Eun Park ◽

Yeo-Jin Park ◽

...

Keyword(s):

Adipose Tissue ◽

Coordinated Control ◽

Ampk Signaling ◽

Obese Rats

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Aurora-A-mediated phosphorylation of LKB1 compromises LKB1/AMPK signaling axis to facilitate NSCLC growth and migration

Oncogene ◽

10.1038/onc.2017.354 ◽

2017 ◽

Vol 37 (4) ◽

pp. 502-511 ◽

Cited By ~ 12

Author(s):

X Zheng ◽

J Chi ◽

J Zhi ◽

H Zhang ◽

D Yue ◽

...

Keyword(s):

Aurora A ◽

Ampk Signaling ◽

Signaling Axis ◽

And Migration

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Drosophila PDGF/VEGF signaling from muscles to hepatocyte-like cells protects against obesity

10.1101/2019.12.23.887059 ◽

2019 ◽

Cited By ~ 1

Author(s):

Arpan C. Ghosh ◽

Sudhir G. Tattikota ◽

Yifang Liu ◽

Aram Comjean ◽

Yanhui Hu ◽

...

Keyword(s):

Adipose Tissue ◽

Lipid Synthesis ◽

Rapid Expansion ◽

List Type ◽

Tissue Lipid ◽

Mature Adult ◽

Signaling Axis ◽

Organ Specific ◽

Lipid Stores ◽

Multicellular Organisms

AbstractPDGF/VEGF ligands regulate a plethora of biological processes in multicellular organisms via autocrine, paracrine and endocrine mechanisms. Here, we investigated organ-specific roles of Drosophila PDGF/VEGF-like factors (Pvfs). We combine genetic approaches and single-nuclei sequencing to demonstrate that muscle-derived Pvf1 signals to the Drosophila hepatocyte-like cells/oenocytes to suppress lipid synthesis by activating the Pi3K/Akt1/mTOR signaling cascade in the oenocytes. Additionally, we show that this signaling axis regulates the rapid expansion of adipose tissue lipid stores observed in newly eclosed flies. Flies emerge after pupation with limited adipose tissue lipid stores and lipid levels are progressively restored via lipid synthesis. We find that pvf1 expression in the adult muscle increase rapidly during this stage and that muscle-to-oenocyte Pvf1 signaling inhibits restoration of adipose tissue lipid stores as the process reaches completion. Our findings provide the first evidence in a metazoan of a PDGF/VEGF ligand acting as a myokine that regulates systemic lipid homeostasis by activating mTOR in hepatocyte-like cells.HighlightsMuscle specific Pvf1 protects mature adult flies from obesitySingle-nuclei RNA sequencing reveals that PvR, the receptor for Pvf1, is highly expressed in the Drosophila hepatocyte-like cells/oenocytes.PvR is required specifically in oenocytes to protect adult flies from obesityMuscle-to-oenocyte Pvf1 signaling activates PvR/Pi3K/Akt1/mTOR in the oenocytes to suppress lipid synthesisMuscle-derived Pvf1 helps terminate the rapid expansion of adipose tissue lipid stores in newly eclosed flies

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