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Suppressing adipocy...
Suppressing adipocyte inflammation promotes insulin resistance in mice
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Zhu, Q. (författare)
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An, Y. A. (författare)
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Kim, M. (författare)
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Zhang, Z. (författare)
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Zhao, S. (författare)
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Zhu, Y. (författare)
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- Wernstedt Asterholm, Ingrid, 1978 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Kusminski, C. M. (författare)
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Scherer, P. E. (författare)
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(creator_code:org_t)
- Elsevier BV, 2020
- 2020
- Engelska.
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Ingår i: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 39
- Relaterad länk:
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https://doi.org/10.1...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Objective: Obesity-induced insulin resistance is closely associated with chronic subclinical inflammation in white adipose tissue. However, the mechanistic involvement of adipocyte-derived inflammation under these disease conditions remains unclear. Our aim was to investigate the relative inflammation-related contributions of adipocytes and macrophages to insulin sensitivity. Methods: RIDα/β is an adenoviral protein complex that inhibits several inflammatory pathways, including TLR4, TNFα, and IL1β signaling. We generated novel mouse models with adipocyte-specific and macrophage-specific doxycycline (dox)-inducible RIDα/β-transgenic mice (RIDad and RIDmac mice, respectively). Results: RIDα/β induction significantly reduced LPS-stimulated inflammatory markers, such as Tnf, Il1b, and Saa3 in adipose tissues. Surprisingly, RIDad mice had elevated levels of postprandial glucose and insulin and exhibited glucose intolerance and insulin resistance, even under chow-fed conditions. Moreover, the RIDad mice displayed further insulin resistance under obesogenic (high-fat diet, HFD) conditions despite reduced weight gain. In addition, under pre-existing obese and inflamed conditions on an HFD, subsequent induction of RIDα/β in RIDad mice reduced body weight gain, further exacerbating glucose tolerance, enhancing insulin resistance and fatty liver, and reducing adiponectin levels. This occurred despite effective suppression of the inflammatory pathways (including TNFα and IL1β). In contrast, RIDmac mice, upon HFD feeding, displayed similar weight gain, comparable adiponectin levels, and insulin sensitivity, suggesting that the inflammatory properties of macrophages did not exert a negative impact on metabolic readouts. RIDα/β expression and the ensuing suppression of inflammation in adipocytes enhanced adipose tissue fibrosis and reduced vascularization. Conclusion: Our novel findings further corroborate our previous observations suggesting that suppressing adipocyte inflammation impairs adipose tissue function and promotes insulin resistance, despite beneficial effects on weight gain. © 2020 The Authors
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Nyckelord
- Adipocyte
- Inflammation
- Insulin resistance
- adiponectin
- doxycycline
- interleukin 1beta
- receptor internalization and degradation alpha beta
- toll like receptor 4
- tumor necrosis factor
- unclassified drug
- viral protein
- adipose tissue
- adult
- animal cell
- animal experiment
- animal model
- animal tissue
- Article
- body weight gain
- controlled study
- fatty liver
- gene
- glucose intolerance
- Il1b gene
- insulin sensitivity
- macrophage
- mouse
- nonhuman
- obesity
- postprandial state
- priority journal
- protein expression
- Saa3 gene
- TLR signaling
- Tnf gene
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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