Suppression of GATA-3 increases adipogenesis, reduces inflammation and improves insulin sensitivity in 3T3L-1 preadipocytes
<p dir="ltr">Impaired adipogenesis plays an important role in the development of obesity-associated insulin resistance and type 2 diabetes. Adipose tissue inflammation is a crucial mediator of this process. GATA-3 plays important roles in adipogenesis and inflammation. The aim of thi...
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2020
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| _version_ | 1864513559026728960 |
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| author | Layla Al-Mansoori (9522518) |
| author2 | Hend Al-Jaber (9522521) Aisha Y. Madani (14152911) Nayef A. Mazloum (7355087) Abdelali Agouni (181926) Manjunath Ramanjaneya (519259) Abdul-Badi Abou-Samra (3411167) Mohamed A. Elrayess (7956179) |
| author2_role | author author author author author author author |
| author_facet | Layla Al-Mansoori (9522518) Hend Al-Jaber (9522521) Aisha Y. Madani (14152911) Nayef A. Mazloum (7355087) Abdelali Agouni (181926) Manjunath Ramanjaneya (519259) Abdul-Badi Abou-Samra (3411167) Mohamed A. Elrayess (7956179) |
| author_role | author |
| dc.creator.none.fl_str_mv | Layla Al-Mansoori (9522518) Hend Al-Jaber (9522521) Aisha Y. Madani (14152911) Nayef A. Mazloum (7355087) Abdelali Agouni (181926) Manjunath Ramanjaneya (519259) Abdul-Badi Abou-Samra (3411167) Mohamed A. Elrayess (7956179) |
| dc.date.none.fl_str_mv | 2020-11-01T00:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.cellsig.2020.109735 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Suppression_of_GATA-3_increases_adipogenesis_reduces_inflammation_and_improves_insulin_sensitivity_in_3T3L-1_preadipocytes/24225712 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Clinical sciences Pharmacology and pharmaceutical sciences GATA-3 suppression Adipogenesis Inflammation Insulin resistance Target validation |
| dc.title.none.fl_str_mv | Suppression of GATA-3 increases adipogenesis, reduces inflammation and improves insulin sensitivity in 3T3L-1 preadipocytes |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Impaired adipogenesis plays an important role in the development of obesity-associated insulin resistance and type 2 diabetes. Adipose tissue inflammation is a crucial mediator of this process. GATA-3 plays important roles in adipogenesis and inflammation. The aim of this study is to investigate the impact of GATA-3 suppression on improving adipogenesis, lowering inflammation and reversing insulin resistance. GATA-3 levels were measured in subcutaneous (SC) and omental (OM) adipose tissues obtained from insulin sensitive (IS) and insulin resistant (IR) obese individuals during weight reduction surgeries. The effect of GATA-3 suppression on adipogenesis, expression of inflammatory cytokines and insulin resistance biomarkers was performed in 3T3L-1 mouse preadipocytes <i>via</i> transfection with GATA-3-specific DNAzyme. GATA-3 expression was higher in OM compared to SC adipose tissues and in stromal vascular fraction-derived differentiating preadipocytes from IR obese individuals compared to their IS counterparts. Suppression of GATA-3 expression in 3T3L-1 mouse preadipocytes with GATA-3 specific inhibitor reversed 4-hydroxynonenal-induced impaired adipogenesis and triggered changes in the expression of insulin signaling-related genes. GATA-3 inhibition also modulated the expression of IL-6 and IL-10 and lowered the expression of insulin resistance biomarkers (PAI-1 and resistin) and insulin resistance phosphoproteins (p-BAD, p-PTEN and p-GSK3β). Inhibiting GATA-3 improves adipocytes differentiation, modulates the secretion of inflammatory cytokines and improves insulin sensitivity in insulin resistant cells. Suppression of GATA-3 could be a promising tool to improve adipogenesis, restore insulin sensitivity and lower obesity-associated inflammation in insulin resistant individuals.</p><h2>Other Information</h2><p dir="ltr">Published in: Cellular Signalling<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.cellsig.2020.109735" target="_blank">https://dx.doi.org/10.1016/j.cellsig.2020.109735</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_ade862cd8cfa9db5a51ba112114bd9bd |
| identifier_str_mv | 10.1016/j.cellsig.2020.109735 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/24225712 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Suppression of GATA-3 increases adipogenesis, reduces inflammation and improves insulin sensitivity in 3T3L-1 preadipocytesLayla Al-Mansoori (9522518)Hend Al-Jaber (9522521)Aisha Y. Madani (14152911)Nayef A. Mazloum (7355087)Abdelali Agouni (181926)Manjunath Ramanjaneya (519259)Abdul-Badi Abou-Samra (3411167)Mohamed A. Elrayess (7956179)Biological sciencesBiochemistry and cell biologyBiomedical and clinical sciencesClinical sciencesPharmacology and pharmaceutical sciencesGATA-3 suppressionAdipogenesisInflammationInsulin resistanceTarget validation<p dir="ltr">Impaired adipogenesis plays an important role in the development of obesity-associated insulin resistance and type 2 diabetes. Adipose tissue inflammation is a crucial mediator of this process. GATA-3 plays important roles in adipogenesis and inflammation. The aim of this study is to investigate the impact of GATA-3 suppression on improving adipogenesis, lowering inflammation and reversing insulin resistance. GATA-3 levels were measured in subcutaneous (SC) and omental (OM) adipose tissues obtained from insulin sensitive (IS) and insulin resistant (IR) obese individuals during weight reduction surgeries. The effect of GATA-3 suppression on adipogenesis, expression of inflammatory cytokines and insulin resistance biomarkers was performed in 3T3L-1 mouse preadipocytes <i>via</i> transfection with GATA-3-specific DNAzyme. GATA-3 expression was higher in OM compared to SC adipose tissues and in stromal vascular fraction-derived differentiating preadipocytes from IR obese individuals compared to their IS counterparts. Suppression of GATA-3 expression in 3T3L-1 mouse preadipocytes with GATA-3 specific inhibitor reversed 4-hydroxynonenal-induced impaired adipogenesis and triggered changes in the expression of insulin signaling-related genes. GATA-3 inhibition also modulated the expression of IL-6 and IL-10 and lowered the expression of insulin resistance biomarkers (PAI-1 and resistin) and insulin resistance phosphoproteins (p-BAD, p-PTEN and p-GSK3β). Inhibiting GATA-3 improves adipocytes differentiation, modulates the secretion of inflammatory cytokines and improves insulin sensitivity in insulin resistant cells. Suppression of GATA-3 could be a promising tool to improve adipogenesis, restore insulin sensitivity and lower obesity-associated inflammation in insulin resistant individuals.</p><h2>Other Information</h2><p dir="ltr">Published in: Cellular Signalling<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.cellsig.2020.109735" target="_blank">https://dx.doi.org/10.1016/j.cellsig.2020.109735</a></p>2020-11-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.cellsig.2020.109735https://figshare.com/articles/journal_contribution/Suppression_of_GATA-3_increases_adipogenesis_reduces_inflammation_and_improves_insulin_sensitivity_in_3T3L-1_preadipocytes/24225712CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/242257122020-11-01T00:00:00Z |
| spellingShingle | Suppression of GATA-3 increases adipogenesis, reduces inflammation and improves insulin sensitivity in 3T3L-1 preadipocytes Layla Al-Mansoori (9522518) Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Clinical sciences Pharmacology and pharmaceutical sciences GATA-3 suppression Adipogenesis Inflammation Insulin resistance Target validation |
| status_str | publishedVersion |
| title | Suppression of GATA-3 increases adipogenesis, reduces inflammation and improves insulin sensitivity in 3T3L-1 preadipocytes |
| title_full | Suppression of GATA-3 increases adipogenesis, reduces inflammation and improves insulin sensitivity in 3T3L-1 preadipocytes |
| title_fullStr | Suppression of GATA-3 increases adipogenesis, reduces inflammation and improves insulin sensitivity in 3T3L-1 preadipocytes |
| title_full_unstemmed | Suppression of GATA-3 increases adipogenesis, reduces inflammation and improves insulin sensitivity in 3T3L-1 preadipocytes |
| title_short | Suppression of GATA-3 increases adipogenesis, reduces inflammation and improves insulin sensitivity in 3T3L-1 preadipocytes |
| title_sort | Suppression of GATA-3 increases adipogenesis, reduces inflammation and improves insulin sensitivity in 3T3L-1 preadipocytes |
| topic | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Clinical sciences Pharmacology and pharmaceutical sciences GATA-3 suppression Adipogenesis Inflammation Insulin resistance Target validation |