Activation of the adipocyte CREB/CRTC pathway in obesity

Yoon, Young-Sil; Liu, Weiyi; Velde, Sam Van de; Matsumura, Shigenobu; Wiater, Ezra; Huang, Ling; Montminy, Marc

doi:10.1038/s42003-021-02735-5

Cited by 23 publications

(11 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to this, early reports described that SIK2 was upregulated in white adipose tissue from db/db mice, suggesting differences in the regulation of SIK2 expression in human versus rodent obesity [3]. However, our novel data showing a marked reduction of SIK2 levels in adipocytes from ob/ob mice, as well as a recent paper showing reduced SIK2 in white adipose tissue from highfat diet-fed mice [21], indicate that SIK2 is indeed downregulated in rodent obesity. Based on pan-SIK inhibition in primary adipocytes from humans, mice, and rats, our study also supports that SIK isoforms are functionally similar across species, at least regarding effects on insulin signaling and glucose uptake.…”

Section: Discussioncontrasting

confidence: 85%

Salt‐inducible kinases are required for glucose uptake and insulin signaling in human adipocytes

Säll,

Lindahl,

Fritzen

et al. 2023

Obesity

View full text Add to dashboard Cite

ObjectiveSalt‐inducible kinase 2 (SIK2) is abundantly expressed in adipocytes and downregulated in adipose tissue from individuals with obesity or insulin resistance. The main aims of this work were to investigate the involvement of SIKs in the regulation of glucose uptake in primary mature human adipocytes and to identify mechanisms underlying this regulation.MethodsPrimary mature adipocytes were isolated from human, rat, or mouse adipose tissue and treated with pan‐SIK inhibitors. Adipocytes isolated from wild type, ob/ob, and SIK2 knockout mice were also used. Glucose uptake was examined by glucose tracer assay. The insulin signaling pathway was monitored by Western blotting, co‐immunoprecipitation, and total internal reflection fluorescence microscopy.ResultsThis study demonstrates that SIK2 is downregulated in obese ob/ob mice and that SIK activity is required for intact glucose uptake in primary human and mouse adipocytes. The underlying mechanism involves direct effects on the insulin signaling pathway, likely at the level of phosphatidylinositol (3,4,5)‐trisphosphate (PIP3) generation or breakdown. Moreover, lack of SIK2 alone is sufficient to attenuate glucose uptake in mouse adipocytes.ConclusionsSIK2 is required for insulin action in human adipocytes, and the mechanism includes direct effects on the insulin signaling pathway.

show abstract

Section: Discussioncontrasting

confidence: 85%

Salt‐inducible kinases are required for glucose uptake and insulin signaling in human adipocytes

Säll,

Lindahl,

Fritzen

et al. 2023

Obesity

View full text Add to dashboard Cite

show abstract

“…LGALS3 is an essential regulator of insulin resistance, fibrosis and inflammation cytokines including TNF- α , IL-6 and IL-1 β , and has been shown to participate in glucose intolerance and lipid metabolism disorders ( Li et al, 2020b ; Yu et al, 2021 ). CREB1 has been found to promote insulin resistance ( Yoon et al, 2021 ) and ESR1 is associated with adiposity and mitochondrial metabolism ( Zhou et al, 2020c ). These targets were considered the putative key targets of SGXZ decoction for the treatment of NAFLD.…”

Section: Resultsmentioning

confidence: 99%

Investigation of the potential mechanism of the Shugan Xiaozhi decoction for the treatment of nonalcoholic fatty liver disease based on network pharmacology, molecular docking and molecular dynamics simulation

Yang

Jiang

et al. 2022

PeerJ

View full text Add to dashboard Cite

Background Nonalcoholic fatty liver disease (NAFLD) is a metabolic disease, the incidence of which increases annually. Shugan Xiaozhi (SGXZ) decoction, a composite traditional Chinese medicinal prescription, has been demonstrated to exert a therapeutic effect on NAFLD. In this study, the potential bioactive ingredients and mechanism of SGXZ decoction against NAFLD were explored via network pharmacology, molecular docking, and molecular dynamics simulation. Methods Compounds in SGXZ decoction were identified and collected from the literature, and the corresponding targets were predicted through the Similarity Ensemble Approach database. Potential targets related to NAFLD were searched on DisGeNET and GeneCards databases. The compound–target–disease and protein-protein interaction (PPI) networks were constructed to recognize key compounds and targets. Functional enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed on the targets. Molecular docking was used to further screen the potent active compounds in SGXZ. Finally, molecular dynamics (MD) simulation was applied to verify and validate the binding between the most potent compound and targets. Results A total of 31 active compounds and 220 corresponding targets in SGXZ decoction were collected. Moreover, 1,544 targets of NAFLD were obtained, of which 78 targets intersected with the targets of SGXZ decoction. Key compounds and targets were recognized through the compound–target–disease and PPI network. Multiple biological pathways were annotated, including PI3K-Akt, MAPK, insulin resistance, HIF-1, and tryptophan metabolism. Molecular docking showed that gallic acid, chlorogenic acid and isochlorogenic acid A could combine with the key targets. Molecular dynamics simulations suggested that isochlorogenic acid A might potentially bind directly with RELA, IL-6, VEGFA, and MMP9 in the regulation of PI3K–Akt signaling pathway. Conclusion This study investigated the active substances and key targets of SGXZ decoction in the regulation of multiple-pathways based on network pharmacology and computational approaches, providing a theoretical basis for further pharmacological research into the potential mechanism of SGXZ in NAFLD.

show abstract

“…Furthermore, the CXCL1 promoter contains an NF-κB binding site, making it susceptible to regulation by the NF-κB signaling pathway, which has been shown to play a crucial role in both psoriasis and obesity. [36][37] (7) Secreted Phosphoprotein 1 (SPP1), also known as Osteopontin (OPN): SPP1 plays a crucial role in early immune responses and pathological processes. Its expression is influenced by IL-1, TGF-β, and it possesses various biological functions, including stimulating T cell proliferation, promoting cytokine secretion, accelerating angiogenesis, inhibiting endothelial cell apoptosis, and inducing monocyte differentiation.…”

Section: Discussionmentioning

confidence: 99%

Exploring the comorbidity mechanisms between psoriasis and obesity based on bioinformatics

Gao,

2024

Skin Research and Technology

View full text Add to dashboard Cite

BackgroundPsoriasis is a chronic, recurrent, immune‐mediated inflammatory skin disease characterized by erythematous scaly lesions. Obesity is currently a major global health concern, increasing the risk of diseases such as cardiovascular diseases and diabetes. Since the correlation between psoriasis and obesity, as well as hypertension, diabetes, and cardiovascular diseases, has been clinically evidenced, it is of certain clinical significance to explore the mechanisms underlying the comorbidity of psoriasis with these conditions.Materials and methodsGene targets for both diseases were obtained from the Gene Expression Omnibus (GEO) comprehensive gene expression database. Differential gene analysis, intersection gene analysis, construction and visualization of protein‐protein interaction networks (PPI) using R software, Cytoscape 3.8.2 software, online tools such as String, and enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed, with relevant graphics generated.ResultsAnalysis identified 29 intersecting genes between the two diseases, with 10 key targets such as S100A7 and SERPINB4. Enrichment analysis indicated their involvement in regulating biological processes such as leukocyte chemotaxis, migration, and chronic inflammatory responses through cellular structures such as intracellular vesicles and extracellular matrix. Molecular functions, including RAGE receptor binding, Toll‐like receptor binding, and fatty acid binding, were found to simultaneously regulate psoriasis and obesity.ConclusionPsoriasis and obesity may mutually influence each other through multiple targets and pathways, emphasizing the importance of considering comorbidity treatment and daily care in clinical practice.

show abstract

Activation of the adipocyte CREB/CRTC pathway in obesity

Cited by 23 publications

References 59 publications

Salt‐inducible kinases are required for glucose uptake and insulin signaling in human adipocytes

Salt‐inducible kinases are required for glucose uptake and insulin signaling in human adipocytes

Investigation of the potential mechanism of the Shugan Xiaozhi decoction for the treatment of nonalcoholic fatty liver disease based on network pharmacology, molecular docking and molecular dynamics simulation

Exploring the comorbidity mechanisms between psoriasis and obesity based on bioinformatics

Contact Info

Product

Resources

About