Hepatic PPARγ and LXRα independently regulate lipid accumulation in the livers of genetically obese mice

•The role of hepatic PPARγ in LXRα-associated fat accumulation was determined using mice lacking hepatic PPARγ.•The LXR-specific ligand T0901317 was administered to normal or obesity model mice lacking hepatic PPARγ.•The T0901317 increased development of fatty liver in mice lacking hepatic PPARγ.•Pa...

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Bibliographic Details
Published in:FEBS letters 2014-06, Vol.588 (14), p.2277-2281
Main Authors: Matsusue, Kimihiko, Aibara, Daisuke, Hayafuchi, Risa, Matsuo, Kohei, Takiguchi, Soichi, Gonzalez, Frank J., Yamano, Shigeru
Format: Article
Language:English
Subjects:
Animals
Anticholesteremic Agents - pharmacology
Blood Glucose
Fatty liver
Fatty Liver - metabolism
hepatocyte-specific PPARγ knockout
Hydrocarbons, Fluorinated - pharmacology
Hypoglycemic Agents - pharmacology
Lipogenesis
Liver - metabolism
Liver - pathology
Liver X receptor α
Liver X Receptors
LXRα
Mice
Mice, Knockout
Mice, Obese
normal genetic background
OB/OB
obese genetic background
Orphan Nuclear Receptors - agonists
Orphan Nuclear Receptors - physiology
Peroxisome proliferator-activated receptor γ
PPAR gamma - physiology
PPARγ
Pparγ WT
Pparγ ΔH
Sulfonamides - pharmacology
wild-type PPARγ
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Summary:•The role of hepatic PPARγ in LXRα-associated fat accumulation was determined using mice lacking hepatic PPARγ.•The LXR-specific ligand T0901317 was administered to normal or obesity model mice lacking hepatic PPARγ.•The T0901317 increased development of fatty liver in mice lacking hepatic PPARγ.•Pathways involving LXRα and PPARγ independently accelerated its development. The nuclear hormone receptors liver X receptor α (LXRα) and peroxisome proliferator-activated receptor γ (PPARγ) play key roles in the development of fatty liver. To determine the link between hepatic PPARγ and LXRα signaling and the development of fatty liver, a LXRα-specific ligand, T0901317, was administered to normal OB/OB and genetically obese (ob/ob) mice lacking hepatic PPARγ (PparγΔH). In ob/ob-PparγΔH and OB/OB-PparγΔH mice, as well as ob/ob-PparγWT and OB/OB-PparγWT mice, the liver weights and hepatic triglyceride levels were markedly increased in response to T0901317 treatment. These results suggest that hepatic PPARγ and LXRα signals independently contribute to the development of fatty liver.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2014.05.012