The orphan nuclear receptor, RORalpha, regulates gene expression that controls lipid metabolism: staggerer (SG/SG) mice are resistant to diet-induced obesity.

@article{Lau2008TheON,
  title={The orphan nuclear receptor, RORalpha, regulates gene expression that controls lipid metabolism: staggerer (SG/SG) mice are resistant to diet-induced obesity.},
  author={Patrick Lau and Rebecca L. Fitzsimmons and Suryaprakash Raichur and Shu-Ching Mary Wang and Adriane Lechtken and George E. O. Muscat},
  journal={The Journal of biological chemistry},
  year={2008},
  volume={283 26},
  pages={
          18411-21
        }
}
Homozygous staggerer mice (sg/sg) display decreased and dysfunctional retinoic acid receptor-related orphan receptor alpha (RORalpha) expression. We observed decreases in serum (and liver) triglycerides and total and high density lipoprotein serum cholesterol in sg/sg mice. Moreover, the sg/sg mice were characterized by reduced adiposity (associated with decreased fat pad mass and adipocyte size). Candidate-based expression profiling demonstrated that the dyslipidemia in sg/sg mice is… 
Transcriptional profiling reveals a role for RORalpha in regulating gene expression in obesity-associated inflammation and hepatic steatosis.
TLDR
It is demonstrated that RORα-deficient staggerer mice fed with a high-fat diet (HFD) exhibited reduced adiposity and hepatic triglyceride levels compared with wild-type littermates and were resistant to the development of hepatic steatosis, adipose-associated inflammation, and insulin resistance.
RORα and 25-Hydroxycholesterol Crosstalk Regulates Lipid Droplet Homeostasis in Macrophages
TLDR
It is demonstrated that macrophages from sg/sg mice have increased ability to accumulate lipids and accordingly exhibit larger lipid droplets (LD), and 25HC and RORα signify a new pathway involved in the regulation of lipid homeostasis in macrophage, potentially via increased uptake of lipid which is suggested by mRNA expression changes in Vldlr and other related genes.
Disruption of Rorα1 and cholesterol 25-hydroxylase expression attenuates phagocytosis in male Rorαsg/sg mice.
TLDR
It is proposed that 25HC is essential for optimizing membrane internalization during phagocytosis and that aberrant Ch25h expression in Rorα1-deficient sg/sg macrophages disrupts phagocytes, heralding a wider and essential role for this oxysterol at the nexus of metabolism and immunity.
Rorα deficiency and decreased adiposity are associated with induction of thermogenic gene expression in subcutaneous white adipose and brown adipose tissue.
TLDR
It is suggested that enhanced Ucp1 and thermogenic gene expression/activity may be an important contributor to the lean, obesity-resistant phenotype in Rorα-deficient mice.
Homozygous staggerer (sg/sg) mice display improved insulin sensitivity and enhanced glucose uptake in skeletal muscle
TLDR
It is proposed that Rorα plays an important role in regulation of the AKT2 signalling cascade, which controls glucose uptake in skeletal muscle, in sg/sg mice relative to wild-type littermates.
The nuclear retinoid-related orphan receptor-α regulates adipose tissue glyceroneogenesis in addition to hepatic gluconeogenesis.
TLDR
Results indicated that both adipocyte glyceroneogenesis and hepatocyte gluconeogenesis were regulated by RORα, demonstrating the physiological function of ROR α in regulating both glucose and FFA homeostasis.
The orphan nuclear receptor RORalpha restrains adipocyte differentiation through a reduction of C/EBPbeta activity and perilipin gene expression.
TLDR
It is shown that RORalpha inhibits the transcriptional activity of CCAAT/enhancer-binding protein beta without affecting its expression, thereby blocking the induction of both PPARgamma and C/EBPalpha, resulting in the suppression of C/EBPbeta-dependent adipogenesis.
Identification and validation of the pathways and functions regulated by the orphan nuclear receptor, ROR alpha1, in skeletal muscle
TLDR
It is proposed that RORα1 is involved in regulating the Akt2-AMPK signaling pathways in the context of lipid homeostasis in skeletal muscle.
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References

SHOWING 1-10 OF 58 REFERENCES
RORalpha regulates the expression of genes involved in lipid homeostasis in skeletal muscle cells: caveolin-3 and CPT-1 are direct targets of ROR.
TLDR
It is speculated that ROR agonists would increase fatty acid catabolism in muscle and suggest selective activators of ROR may have therapeutic utility in the treatment of obesity and atherosclerosis.
Transcriptional Regulation of Apolipoprotein C-III Gene Expression by the Orphan Nuclear Receptor RORα*
TLDR
RORα is identified as a transcriptional regulator of apo C-III gene expression, providing a novel, physiological role for RORα1 in the regulation of genes controlling triglyceride metabolism.
The orphan nuclear receptor, NOR-1, a target of beta-adrenergic signaling, regulates gene expression that controls oxidative metabolism in skeletal muscle.
TLDR
It is shown that beta2-AR agonist treatment significantly and transiently activated the expression of NOR-1 (and the other members of the NR4A subgroup) in slow-twitch oxidative soleus muscle and fast-twitch glycolytic tibialis anterior muscle, and that NOR- 1 is recruited to the lipin-1alpha and PDK-4 promoters, and this is consistent withNOR-1-mediated regulation of these genes.
Ablation of the cholesterol transporter adenosine triphosphate-binding cassette transporter G1 reduces adipose cell size and protects against diet-induced obesity.
TLDR
The data indicate a previously unrecognized role of ABCG1 in the regulation of energy balance and triglyceride storage and the reduction of adipose tissue mass in Abcg1-/- mice was associated with markedly decreased size of the adipocytes.
The Liver X Receptor (LXR) and Hepatic Lipogenesis
  • J. Cha, J. Repa
  • Biology, Chemistry
    Journal of Biological Chemistry
  • 2007
TLDR
This report identifies the carbohydrate response element-binding protein (ChREBP) as an LXR target that independently enhances the up-regulation of select lipogenic genes and establishes LXR as a master lipogenic transcription factor, as it directly regulates both SREBP-1c and ChREBP to enhance hepatic fatty acid synthesis.
Severe atherosclerosis and hypoalphalipoproteinemia in the staggerer mouse, a mutant of the nuclear receptor RORalpha.
TLDR
It is suggested that the RORalpha gene contributes to the plasma HDL level and susceptibility to atherosclerosis.
Transcriptional Regulation of Apolipoprotein A-I Gene Expression by the Nuclear Receptor RORα*
TLDR
Data indicate a novel, physiological role for RORα1 in the regulation of genes involved in lipid and lipoprotein metabolism and possibly in the development of metabolic diseases, such as atherosclerosis.
Regulation of SREBP-1 expression and transcriptional action on HKII and FAS genes during fasting and refeeding in rat tissues Published, JLR Papers in Press, January 1, 2005. DOI 10.1194/jlr.M400261-JLR200
TLDR
The data elucidate the important role of SREBP-1 not only in the regulation of lipid metabolism but also of glucose metabolism and energy homeostasis as well as the response of FAS and HKII genes to nutritional regulation in rodents.
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