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A hypothesis for in...
A hypothesis for insulin resistance in primary human adipocytes involving MRTF-A and suppression of PPARγ
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- Hansson, Björn (author)
- Lund University,Lunds universitet,Glukostransport och proteintrafficking,Forskargrupper vid Lunds universitet,Glucose Transport and Protein Trafficking,Lund University Research Groups
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- Schumacher, Sara (author)
- Lund University
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- Fryklund, Claes (author)
- Lund University,Lunds universitet,Glukostransport och proteintrafficking,Forskargrupper vid Lunds universitet,Glucose Transport and Protein Trafficking,Lund University Research Groups
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- Morén, Björn (author)
- Lund University,Lunds universitet,Glukostransport och proteintrafficking,Forskargrupper vid Lunds universitet,Glucose Transport and Protein Trafficking,Lund University Research Groups
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- Björkqvist, Maria (author)
- Lund University,Lunds universitet,Biomarkörer vid hjärnsjukdomar,Forskargrupper vid Lunds universitet,Biomarkers in Brain Disease,Lund University Research Groups
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- Swärd, Karl (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Cellular Biomechanics,Lund University Research Groups
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- Stenkula, Karin G. (author)
- Lund University,Lunds universitet,Glukostransport och proteintrafficking,Forskargrupper vid Lunds universitet,Glucose Transport and Protein Trafficking,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2020
- 2020
- English 6 s.
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In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X. ; 533:1, s. 64-69
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Abstract
Subject headings
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- Obesity is the main risk factor behind insulin resistance and type 2 diabetes. Still, the mechanism behind adipocyte dysfunction is not yet resolved. Recently, we reported that rapid actin remodeling correlates with adipose cell size changes after short-term overfeeding. Therefore, we hypothesized that the actin-driven myocardin-related transcription factor (MRTF-A) contributes to impaired mature adipocyte function. Primary human adipocytes were subjected to adenoviral overexpression of MRTF-A or MRTF-B, followed by Western blot analysis and tracer glucose uptake assay. Further, we assessed cell size distribution, insulin response, MRTF-A localization, actin organization and degree of polymerization in adipocytes isolated from Ob/Ob mice. Overexpression of MRTF-A, but not MRTF-B, markedly suppressed PPARγ expression. Further, MRTF-A expression resulted in decreased IRS-1 level, shifted phosphorylation of Akt (pS473/pT308), IRS-1 (pS302) and AS160 (pT642), and lowered insulin-stimulated glucose uptake. Hypertrophic adipocytes from Ob/Ob mice displayed an increased proportion of polymerized actin, and increased nuclear translocation of MRTF-A compared with control (Ob/+). Similar with human adipocytes overexpressing MRTF-A, adipocytes isolated from Ob/Ob mice had reduced expression of IRS-1 and PPARγ, as well as impaired insulin response. Together, these data demonstrate that MRTF-A negatively influences insulin sensitivity and the expression of key targets in fully mature human adipocytes. This suggests that MRTF-A is poised to exert a transcriptional response in hypertrophic adipocytes, contributing to adipocyte dysfunction and insulin resistance.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Adipocytes
- Glucose transport
- Insulin
- Insulin signaling
- MRTF-A
- Obesity
- PPARγ
Publication and Content Type
- art (subject category)
- ref (subject category)
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