FKBP51 Null Mice Are Resistant to Diet-Induced Obesity and the PPARγ Agonist Rosiglitazone Article Swipe
Lance A. Stechschulte
,
Bin Qiu
,
Manya Warrier
,
Terry D. Hinds
,
Man Zhang
,
Hao Gu
,
Yuxue Xu
,
Saja S. Khuder
,
Lucia Russo
,
Sonia M. Najjar
,
Beata Lecka‐Czernik
,
Weidong Yong
,
Edwin R. Sánchez
·
YOU?
·
· 2016
· Open Access
·
· DOI: https://doi.org/10.1210/en.2015-1996
YOU?
·
· 2016
· Open Access
·
· DOI: https://doi.org/10.1210/en.2015-1996
FK506-binding protein-51 (FKBP51) is a molecular cochaperone recently shown to be a positive regulator of peroxisome proliferator-activated receptor (PPAR)γ, the master regulator of adipocyte differentiation and function. In cellular models of adipogenesis, loss of FKBP51 not only reduced PPARγ activity but also reduced lipid accumulation, suggesting that FKBP51 knock-out (KO) mice might have insufficient development of adipose tissue and lipid storage ability. This model was tested by examining wild-type (WT) and FKBP51-KO mice under regular and high-fat diet conditions. Under both diets, FKBP51-KO mice were resistant to weight gain, hepatic steatosis, and had greatly reduced white adipose tissue (WAT) but higher amounts of brown adipose tissue. Under high-fat diet, KO mice were highly resistant to adiposity and exhibited reduced plasma lipids and elevated glucose and insulin tolerance. Profiling of perigonadal and sc WAT revealed elevated expression of brown adipose tissue lineage genes in KO mice that correlated increased energy expenditure and a shift of substrate oxidation to carbohydrates, as measured by indirect calorimetry. To directly test PPARγ involvement, WT and KO mice were fed rosiglitazone agonist. In WT mice, rosiglitazone induced whole-body weight gain, increased WAT mass, a shift of substrate oxidation to lipids, and elevated expression of PPARγ-regulated lipogenic genes in WAT. In contrast, KO mice had reduced rosiglitazone responses for these parameters. Our results identify FKBP51 as an important regulator of PPARγ in WAT and as a potential new target in the treatment of obesity and diabetes.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1210/en.2015-1996
- https://academic.oup.com/endo/article-pdf/157/10/3888/10840951/endo3888.pdf
- OA Status
- bronze
- Cited By
- 96
- References
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- Related Works
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- OpenAlex ID
- https://openalex.org/W2490132098
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2490132098Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1210/en.2015-1996Digital Object Identifier
- Title
-
FKBP51 Null Mice Are Resistant to Diet-Induced Obesity and the PPARγ Agonist RosiglitazoneWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2016Year of publication
- Publication date
-
2016-07-21Full publication date if available
- Authors
-
Lance A. Stechschulte, Bin Qiu, Manya Warrier, Terry D. Hinds, Man Zhang, Hao Gu, Yuxue Xu, Saja S. Khuder, Lucia Russo, Sonia M. Najjar, Beata Lecka‐Czernik, Weidong Yong, Edwin R. SánchezList of authors in order
- Landing page
-
https://doi.org/10.1210/en.2015-1996Publisher landing page
- PDF URL
-
https://academic.oup.com/endo/article-pdf/157/10/3888/10840951/endo3888.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
-
https://academic.oup.com/endo/article-pdf/157/10/3888/10840951/endo3888.pdfDirect OA link when available
- Concepts
-
Internal medicine, Endocrinology, Rosiglitazone, Adipogenesis, White adipose tissue, Adipose tissue, Brown adipose tissue, Peroxisome proliferator-activated receptor, Insulin resistance, Chemistry, Adipocyte, Peroxisome, Steatosis, Agonist, Biology, Type 2 diabetes, Receptor, Insulin, Diabetes mellitus, MedicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
96Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 5, 2024: 32, 2023: 11, 2022: 6, 2021: 12Per-year citation counts (last 5 years)
- References (count)
-
56Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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