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Liver-specific RORα deletion does not affect the metabolic susceptibility to western style diet feeding
Antonio Molinaro1, Robert Caesar1, Laurent L'homme2
1Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden.
Objectives:
The nuclear receptor superfamily is a potential target for the development of new treatments for obesity and metabolic diseases. Increasing evidence has pointed towards the retinoic acid-related orphan receptor-alpha (RORα) as an important nuclear receptor involved in several biological processes. RORα full body knockout mice display improved metabolic phenotypes on both chow and high fat (60% fat, 20% carbohydrate) diets, but also have severe behavioral abnormalities. Here we investigated the effect of hepatic RORα by generating mice with liver-specific RORα deletion to elucidate the role of this nuclear receptor on host metabolism.
Methods:
8 week-old mice with liver-specific RORα deletion and littermate controls were fed either chow or western-style diets (40% fat, 40% carbohydrate) for 12 weeks. Metabolic phenotyping was performed at the end of the dietary intervention.
Results:
Here, we show that hepatic RORα deletion does not affect the metabolic susceptibility to either chow or western-style diet in terms of glucose metabolism and adiposity.
Conclusions:
Our data indicate that liver deletion of RORα does not have a pivotal role in the regulation of hepatic glucose and lipid metabolism on chow or western-style diet.
Insights
Deleting retinoic acid-related orphan receptor-alpha (RORα) in the liver does not impact metabolic health. This study found no significant changes in glucose metabolism or adiposity in mice with liver-specific RORα deletion on different diets.
Area of Science:
- Endocrinology
- Metabolic disease research
- Nuclear receptor signaling
Background:
- The nuclear receptor superfamily offers therapeutic targets for obesity and metabolic disorders.
- Retinoic acid-related orphan receptor-alpha (RORα) is implicated in various biological processes.
- Full body RORα knockout mice show improved metabolic phenotypes but exhibit behavioral abnormalities.
Purpose of the Study:
- To investigate the specific role of hepatic RORα in host metabolism.
- To determine the impact of liver-specific RORα deletion on metabolic phenotypes.
- To elucidate the function of RORα in hepatic glucose and lipid metabolism.
Main Methods:
- Generation of mice with liver-specific RORα deletion.
- Dietary intervention with chow or western-style diets (40% fat, 40% carbohydrate) for 12 weeks.
- Comprehensive metabolic phenotyping, including glucose metabolism and adiposity assessment.
Main Results:
- Hepatic RORα deletion did not alter metabolic susceptibility to either diet.
- No significant changes were observed in glucose metabolism or adiposity.
- Liver-specific RORα deletion did not affect weight gain or body composition.
Conclusions:
- Liver deletion of RORα does not play a pivotal role in regulating hepatic glucose and lipid metabolism.
- RORα in the liver is not essential for adaptation to different dietary conditions.
- These findings suggest that targeting hepatic RORα may not be a primary strategy for treating metabolic diseases.
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