Simon W. Beaven

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Dyslipidemia is the sine qua non of atherosclerosis, but it is also strongly associated with the metabolic syndrome, obesity, diabetes, and fatty liver disease. The molecular basis for future therapies requires understanding the pivotal role of nuclear hormone receptors in lipid and inflammatory homeostasis. This review summarizes evidence that the liver X(More)
Impaired estrogen action is associated with the metabolic syndrome in humans. We sought to determine whether impaired estrogen action in female C57Bl6 mice, produced by whole body Esr1 ablation, could recapitulate aspects of this syndrome, including inflammation, insulin resistance, and obesity. Indeed, we found that global knockout (KO) of the estrogen(More)
PURPOSE OF REVIEW Inflammatory bowel disease is characterized by chronic intestinal inflammation in the absence of a recognized pathogen. In its classic description, there are two principal forms of inflammatory bowel disease: Crohn disease and ulcerative colitis. The clinical heterogeneity of these disorders alludes to the possibility of diverse(More)
The liver X receptor alpha (LXRalpha) is a member of the nuclear hormone receptor superfamily that plays an important role in lipid homeostasis. Here we characterize two alternative human LXRalpha transcripts, designated LXRalpha2 and LXRalpha3. All three LXRalpha isoforms are derived from the same gene via alternative splicing and differential promoter(More)
Liver X receptors (LXRs) regulate lipogenesis and inflammation, but their contribution to the metabolic syndrome is unclear. We show that LXRs modulate key aspects of the metabolic syndrome in mice. LXRαβ-deficient-ob/ob (LOKO) mice remain obese but show reduced hepatic steatosis and improved insulin sensitivity compared to ob/ob mice. Impaired hepatic(More)
The most abundant immune cell type is the neutrophil, a key first responder after pathogen invasion. Neutrophil numbers in the periphery are tightly regulated to prevent opportunistic infections and aberrant inflammation. In healthy individuals, more than 1 × 10⁹ neutrophils per kilogram body weight are released from the bone marrow every 24 hours. To(More)
Sexual dimorphism in body weight, fat distribution, and metabolic disease has been attributed largely to differential effects of male and female gonadal hormones. Here, we report that the number of X chromosomes within cells also contributes to these sex differences. We employed a unique mouse model, known as the "four core genotypes," to distinguish(More)
UNLABELLED Liver X receptors (LXRs) are determinants of hepatic stellate cell (HSC) activation and liver fibrosis. Freshly isolated HSCs from Lxrαβ(-/-) mice have increased lipid droplet (LD) size, but the functional consequences of this are unknown. Our aim was to determine whether LXRs link cholesterol to retinoid storage in HSCs and how this impacts(More)
Impaired estrogen receptor α (ERα) action promotes obesity and metabolic dysfunction in humans and mice; however, the mechanisms underlying these phenotypes remain unknown. Considering that skeletal muscle is a primary tissue responsible for glucose disposal and oxidative metabolism, we established that reduced ERα expression in muscle is associated with(More)
BACKGROUND & AIMS Liver X receptors (LXRs) are lipid-activated nuclear receptors with important roles in cholesterol transport, lipogenesis, and anti-inflammatory signaling. Hepatic stellate cells activate during chronic liver injury and mediate the fibrotic response. These cells are also major repositories for lipids, but the role of lipid metabolism(More)