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Reversal of neuronal tau pathology, metabolic dysfunction, and electrophysiological defects via adiponectin pathway-dependent AMPK activation.

ABSTRACT: Reversal of neuronal tau pathology, metabolic dysfunction, and electrophysiological defects via adiponectin pathway-dependent AMPK activation.

PROVIDER: PRJNA1076573 | ENA |

REPOSITORIES: ENA

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Reversal of neuronal tau pathology, metabolic dysfunction, and electrophysiological defects via adiponectin pathway-dependent AMPK activation.

Project description:Changes in brain mitochondrial metabolism are coincident with functional decline; however, direct links between the two have not been established. Here, we show that mitochondrial targeting via the adiponectin receptor activator AdipoRon (AR) clears neurofibrillary tangles (NFTs) and rescues neuronal tauopathy-associated defects. AR reduced levels of phospho-tau and lowered NFT burden by a mechanism involving the energy-sensing kinase AMPK and the growth-sensing kinase GSK3b. The transcriptional response to AR included broad metabolic and functional pathways. Induction of lysosomal pathways involved activation of LC3 and p62, and restoration of neuronal outgrowth required the stress-responsive kinase JNK. Negative consequences of NFTs on mitochondrial activity, ATP production, and lipid stores were corrected. Defects in electrophysiological measures (e.g., resting potential, resistance, spiking profiles) were also corrected. These findings reveal a network linking mitochondrial function, cellular maintenance processes, and electrical aspects of neuronal function that can be targeted via adiponectin receptor activation.

2024-12-09 | GSE255813 | GEO

Uncoupling effects of ERalfa on LKB1/AMPK interaction upon adiponectin exposure in breast cancer

Project description:Adipose tissue is a metabolic and endocrine organ that secretes numerous bioactive molecules called adipocytokines. Among these, adiponectin has been argued to have a crucial role in obesity-associated breast cancer. The key molecule of adiponectin signaling is AMP-activated protein kinase (AMPK), mainly activated by Liver Kinase B1 (LKB1). Here, we demonstrated how the ERalfa/LKB1 interaction may negatively interfere with the capability of LKB1 to phosphorylate AMPK and then inhibit its downstream signaling TSC2/mTOR/p70S6k. In MCF-7 cells upon adiponectin AMPK signaling was not working, keeping its downstream protein Acetyl-CoA Carboxylase (ACC) still active. In contrast, in MDA-MB-231 cells the phosphorylation of AMPK and ACC was enhanced with consequent inhibition of both lipogenesis and cell growth. Thus, upon adiponectin, ERalfa signaling switched the energy balance of breast cancer cells towards a lipogenic phenotype. In other words, adiponectin in all the concentrations tested played an inhibitory role on ERalpha-negative breast cancer cell growth and progression either in vitro or in vivo. In contrast, low adiponectin levels, similar to those circulating in obese patients, worked on ERalfa-positive cells as a growth factor, stimulating their growth and progression. The latter effect seems to be blunted in vivo only in the presence of high adiponectin concentration. Based on the present results, it can be concluded that if we prospectively address adiponectin as a pharmacological tool, a separate therapeutic treatment should be carefully assessed in ERalfa-positive and negative breast-cancer patients.

2020-02-27 | E-MTAB-6120 | biostudies-arrayexpress

Uncoupling effects of ERalfa on LKB1/AMPK interaction upon adiponectin exposure in breast cancer

Project description:Uncoupling effects of ERalfa on LKB1/AMPK interaction upon adiponectin exposure in breast cancer

| PRJEB36821 | ENA

Gene regulation by full length human adiponectin

Project description:Transcriptionnal profiling of 4 human cell lines treated during 3 hours with human adiponectin Keywords: transcriptionnal analysis Four human cell lines (Hela, HepG2, Panc-1, Hek293) were grown until confluence. These cell lines were serum depleted during 2 hours and then treated with human adiponectin (2,5 µg/ml) during 3 hours. Each adiponectin stimulated cell line was compared to depleted cell line. Depleted cell line was considered as control.

2010-12-09 | E-GEOD-14070 | biostudies-arrayexpress

Adipocyte XBP1s regulates systemic insulin sensitivity by modulating adiponectin multimerization

Project description:The physiological role of the spliced form of X-box-binding protein 1 (XBP1s), a key transcription factor of the endoplasmic reticulum (ER) stress response, in adipose tissue remains largely unknown. Here we show that overexpression of XBP1s promotes adiponectin multimerization in adipocytes, thereby regulating systemic glucose homeostasis. Ectopic expression of XBP1s in adipocytes improves glucose tolerance and insulin sensitivity in both lean and obese (ob/ob) mice. The beneficial effect of adipocyte XBP1s on glucose homeostasis is associated with elevated serum levels of HMW adiponectin and indeed, is adiponectin dependent. Mechanistically, XBP1s promotes adiponectin multimerization rather than activating its transcription likely through a direct regulation of the expression of several ER-chaperones involved in adiponectin maturation, including Grp78, Pdia6, ERp44 and DsbA-L. Thus, we conclude that XBP1s is an important regulator of adiponectin multimerization, which may lead to a new therapeutic approach for the treatment of type 2 diabetes and hypoadiponectinemia. Epididymal adipose tissue from wild type and XBP1-overexpressing mice was subjected to gene expression profiling.

2013-11-21 | E-GEOD-36031 | biostudies-arrayexpress

Gene expression analysis in macrophages stimulated 18 h with Adiponectin

Project description:Bone marrow derived macrophages (BMDM) generated from c57bl/6j mice bone marrow cells were stimulated for 18 h with 12 microgram/ml adiponectin, RNA from non-stimulated or 18 h adiponectin-stimulated BMDM subjected to a agilent microarray analysis Three different non-stimulated and 3 different 18 h adiponectin (12 microgram/ml) RNA samples were subjected to a micrrorray analysis

2014-07-03 | E-GEOD-49332 | biostudies-arrayexpress

Expression data from bone marrow cultures treated with adiponectin - evidence for lipopolysaccharide contamination

Project description:The adipocyte-derived hormone adiponectin potently inhibits osteoclast formation in vitro. Gene expression profiling of murine bone marrow cells treated with adiponectin was used to identify candidate genes that mediate the effect of adiponectin to inhibit osteoclastogenesis in these cultures. However, we found that contamination by lipopolysaccharide confounds the study of adiponectin activity. Bone marrow cells were cultured for up to five days and RNA was extratced from cells treated with adiponectin and from untreated controls at different time points.

2012-02-02 | E-GEOD-35466 | biostudies-arrayexpress

Zeugodacus tau

Project description:Zeugodacus tau overview

| PRJNA492538 | ENA

Signaling between mammalian adiponectin and a mosquito adiponectin receptor reduces Plasmodium transmission

Project description:Signaling between mammalian adiponectin and a mosquito adiponectin receptor reduces Plasmodium transmission

| PRJNA817525 | ENA

Endogenous renal adiponectin drives gluconeogenesis through enhancing pyruvate and fatty acid utilization

Project description:Adiponectin is an important secretory protein, primarily produced in adipose tissue. However, low but detectable expression of adiponectin can be observed in cell types beyond adipocytes, particularly in kidney tubular cells, but its local renal role is unknown. We assessed the role of renal adiponectin by utilizing male doxycycline inducible kidney tubular cell-specific adiponectin overexpression or knockout mice. Kidney-specific adiponectin overexpression induces a doubling of phosphoenolpyruvate carboxylase expression and enhanced pyruvate-mediated glucose production, tricarboxylic acid cycle intermediates and an upregulation of fatty acid oxidation (FAO). The inhibition of FAO reduces the adiponectin-induced enhancement of glucose production, highlighting the role of FAO in the induction of renal gluconeogenesis. In contrast, kidney-specific adiponectin deleted mice exhibit enhanced glucose tolerance as well as a lower utilization and greater accumulation of lipid species. In summary, renal adiponectin is a potent inducer of gluconeogenesis by driving enhanced FAO in the kidney and underline the important systemic role of renal gluconeogenesis.

2023-09-20 | GSE242095 | GEO

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