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Farnesoid X receptor (FXR) plays an important role in maintaining bile acid and cholesterol homeostasis. Here we demonstrate that FXR also regulates glucose metabolism. Activation of FXR by the synthetic agonist GW4064 or hepatic overexpression of constitutively active FXR by adenovirus-mediated gene transfer significantly lowered blood glucose levels in(More)
The farnesoid X receptor (FXR) is a ligand-activated transcription factor and a member of the nuclear receptor superfamily. In the past six years, remarkable inroads have been made into determining the functional importance of FXR. This receptor has been shown to have crucial roles in controlling bile acid homeostasis, lipoprotein and glucose metabolism,(More)
OBJECTIVE Based on the observation that Fxr-/- mice exhibit a proatherogenic lipoprotein profile, we investigated the role of FXR in the development of atherosclerosis. METHODS AND RESULTS Administration of a western diet to Fxr-/- mice or wild-type mice does not result in the development of significant atherosclerotic lesions. Consequently we generated(More)
Ixabepilone is the first epothilone to be approved for clinical use. Current data suggest the epothilones have a role in treating taxane-resistant cancers and ixabepilone is unaffected by at least some of the mechanisms underlying chemoresistance. Here, we report a series of cytotoxicity and transport studies to assess the potential role of P-glycoprotein(More)
The ventromedial hypothalamus (VMH) is a distinct morphological nucleus involved in feeding, fear, thermoregulation, and sexual activity. It is essentially unknown how VMH circuits underlying these innate responses develop, in part because the VMH remains poorly defined at a cellular and molecular level. Specifically, there is a paucity of(More)
Activation of the farnesoid X receptor (FXRalpha) affects genes controlling many pathways, including those involved in bile acid and glucose homeostasis. Here we report that a critical gene involved in cholesterol homeostasis, Insig-2, was induced when mice or cultured cells were treated with FXRalpha agonists or infected with constitutively active(More)
Sumoylation is generally considered a repressive mark for many transcription factors. However, the in vivo importance of sumoylation for any given substrate remains unclear and is questionable because the extent of sumoylation appears exceedingly low for most substrates. Here, we permanently eliminated SF-1/NR5A1 sumoylation in mice (Sf-1(K119R, K194R, or(More)
Expression of the stimulatory G protein, G(S)alpha, can vary over a 3-fold range in human tissues and in rodent central nervous system. In fact, the offspring of alcoholics have higher levels of G(S)alpha expression in certain tissues compared with the offspring of nonalcoholics. The aim of this research was to test the hypothesis that a causal relationship(More)
Expression of the farnesoid X receptor (FXR; NR1H4) is limited to the liver, intestine, kidney, and adrenal gland. However, the role of FXR in the latter two organs is unknown. In the current study, we performed microarray analysis using RNA from H295R cells infected with constitutively active FXR. Several putative FXR target genes were identified,(More)
The nuclear receptor, farnesoid X receptor (FXR, NR1H4), is known to regulate cholesterol, bile acid, lipoprotein, and glucose metabolism. In the current study, we provide evidence to support a role for FXR in hepatoprotection from acetaminophen (APAP)-induced toxicity. Pharmacological activation of FXR induces the expression of several genes involved in(More)