Hematopoietic Cell-Specific Deletion of Toll-like Receptor 4 Ameliorates Hepatic and Adipose Tissue Insulin Resistance in High-Fat-Fed Mice
(2009) In Cell Metabolism 10(5). p.419-429- Abstract
Chronic low-grade inflammation, particularly in adipose tissue, is an important modulator of obesity-induced insulin resistance. The Toll-like receptor 4 (Tlr4) is a key initiator of inflammatory responses in macrophages. We performed bone marrow transplantation (BMT) of Tlr4lps-del or control C57Bl/10J donor cells into irradiated wild-type C57Bl6 recipient mice to generate hematopoietic cell-specific Tlr4 deletion mutant (BMT-Tlr4-/-) and control (BMT-WT) mice. After 16 weeks of a high-fat diet (HFD), BMT-WT mice developed obesity, hyperinsulinemia, glucose intolerance, and insulin resistance. In contrast, BMT-Tlr4-/- mice became obese but did not develop fasting hyperinsulinemia and had improved hepatic and... (More)
Chronic low-grade inflammation, particularly in adipose tissue, is an important modulator of obesity-induced insulin resistance. The Toll-like receptor 4 (Tlr4) is a key initiator of inflammatory responses in macrophages. We performed bone marrow transplantation (BMT) of Tlr4lps-del or control C57Bl/10J donor cells into irradiated wild-type C57Bl6 recipient mice to generate hematopoietic cell-specific Tlr4 deletion mutant (BMT-Tlr4-/-) and control (BMT-WT) mice. After 16 weeks of a high-fat diet (HFD), BMT-WT mice developed obesity, hyperinsulinemia, glucose intolerance, and insulin resistance. In contrast, BMT-Tlr4-/- mice became obese but did not develop fasting hyperinsulinemia and had improved hepatic and adipose insulin sensitivity during euglycemic clamp studies, compared to HFD BMT-WT controls. HFD BMT-Tlr4-/- mice also showed markedly reduced adipose tissue inflammatory markers and macrophage content. In summary, our results indicate that Tlr4 signaling in hematopoietic-derived cells is important for the development of hepatic and adipose tissue insulin resistance in obese mice.
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- author
- Saberi, Maziyar ; Woods, Niels Bjarne LU ; de Luca, Carl ; Schenk, Simon ; Lu, Juu Chin ; Bandyopadhyay, Gautam ; Verma, Inder M. and Olefsky, Jerrold M.
- organization
- publishing date
- 2009-11-04
- type
- Contribution to journal
- publication status
- published
- keywords
- HUMDISEASE
- in
- Cell Metabolism
- volume
- 10
- issue
- 5
- pages
- 419 - 429
- publisher
- Cell Press
- external identifiers
-
- scopus:70350389389
- pmid:19883619
- ISSN
- 1550-4131
- DOI
- 10.1016/j.cmet.2009.09.006
- language
- English
- LU publication?
- no
- id
- 2fd3bb2f-ab3c-4aac-985f-129f035960bf
- date added to LUP
- 2017-01-24 16:35:49
- date last changed
- 2024-04-19 18:45:38
@article{2fd3bb2f-ab3c-4aac-985f-129f035960bf,
abstract = {{<p>Chronic low-grade inflammation, particularly in adipose tissue, is an important modulator of obesity-induced insulin resistance. The Toll-like receptor 4 (Tlr4) is a key initiator of inflammatory responses in macrophages. We performed bone marrow transplantation (BMT) of Tlr4lps-del or control C57Bl/10J donor cells into irradiated wild-type C57Bl6 recipient mice to generate hematopoietic cell-specific Tlr4 deletion mutant (BMT-Tlr4<sup>-/-</sup>) and control (BMT-WT) mice. After 16 weeks of a high-fat diet (HFD), BMT-WT mice developed obesity, hyperinsulinemia, glucose intolerance, and insulin resistance. In contrast, BMT-Tlr4<sup>-/-</sup> mice became obese but did not develop fasting hyperinsulinemia and had improved hepatic and adipose insulin sensitivity during euglycemic clamp studies, compared to HFD BMT-WT controls. HFD BMT-Tlr4<sup>-/-</sup> mice also showed markedly reduced adipose tissue inflammatory markers and macrophage content. In summary, our results indicate that Tlr4 signaling in hematopoietic-derived cells is important for the development of hepatic and adipose tissue insulin resistance in obese mice.</p>}},
author = {{Saberi, Maziyar and Woods, Niels Bjarne and de Luca, Carl and Schenk, Simon and Lu, Juu Chin and Bandyopadhyay, Gautam and Verma, Inder M. and Olefsky, Jerrold M.}},
issn = {{1550-4131}},
keywords = {{HUMDISEASE}},
language = {{eng}},
month = {{11}},
number = {{5}},
pages = {{419--429}},
publisher = {{Cell Press}},
series = {{Cell Metabolism}},
title = {{Hematopoietic Cell-Specific Deletion of Toll-like Receptor 4 Ameliorates Hepatic and Adipose Tissue Insulin Resistance in High-Fat-Fed Mice}},
url = {{http://dx.doi.org/10.1016/j.cmet.2009.09.006}},
doi = {{10.1016/j.cmet.2009.09.006}},
volume = {{10}},
year = {{2009}},
}