Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0311277 (abdominal obesity)
 2,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic syndrome is an insulin-resistant state that is characterized by a cluster of cardiovascular risk factors, including abdominal obesity, hyperglycemia, elevated blood pressure and combined dyslipidemia. In this review, we discuss the role of the bile-acid-activated farnesoid X receptor (FXR) in the modulation of the metabolic syndrome. Owing to its regulatory actions in lipid and glucose homeostasis, FXR is a potential pharmacological target. Moreover, the observation that FXR also influences endothelial function and atherosclerosis indicates a regulatory role in the cardiovascular complications that are associated with the metabolic syndrome. The pharmacological activation of FXR leads to a complex response that integrates beneficial actions and potentially undesirable side-effects. Thus, the identification of selective FXR modulators (selective bile acid receptor modulators) is required for the development of compounds that can be used to treat the metabolic syndrome.
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PMID:FXR: a promising target for the metabolic syndrome? 1741 31

The metabolic syndrome is a cluster of metabolic disorders, such as abdominal obesity, dyslipidemia, hypertension and impaired fasting glucose that contribute to increased cardiovascular morbidity and mortality. Although the pathogenesis of metabolic syndrome is complicated and the precise mechanisms have not been elucidated, dietary lipids have been recognized as contributory factors in the development and the prevention of cardiovascular risk clustering. This review explores the physiological functions and molecular actions of bioactive lipids, such as n-3 polyunsaturated fatty acids, conjugated fatty acids, sterols, medium-chain fatty acids, diacylglycerols and phospholipids, in the development of metabolic syndrome. Dietary bioactive lipids suppress the accumulation of abdominal adipose tissue and lipids in the liver and serum, and alleviate hypertension and type 2 diabetes through the transcriptional regulation of lipid and glucose metabolism. Peroxisome proliferator-activated receptors (PPARs), sterol regulatory element binding proteins, liver X receptor alpha, retinoid X receptor alpha, farnesoid X receptor alpha, hepatic nuclear factor 4alpha and nuclear factor kappaB contribute to these nuclear actions of bioactive lipids with complex interactions. Recent studies have demonstrated the striking ability of bioactive lipids to regulate the production of physiologically active adipocytokines through PPARgamma activation. In particular, the function of bioactive lipids as dietary adiponectin inducers (dietary insulin sensitizers) deserves attention with respect to alleviation of metabolic syndrome by dietary manipulation.
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PMID:Bioactive lipids in metabolic syndrome. 1817 44

The metabolic syndrome (MetS) is an insulin-resistant state characterized by a cluster of cardiovascular risk factors, including abdominal obesity, hyperglycemia, elevated blood pressure and combined dyslipidemia. In this review, we discuss the potential of farnesoid X receptor (FXR) agonists in the treatment of erectile dysfunction (ED), a multifactorial disorder often comorbid with MetS. FXR not only regulates lipid and glucose homeostasis but also influences endothelial function and atherosclerosis, suggesting a regulatory role for this hormone nuclear receptor in the cardiovascular complications associated with the MetS, including ED. MetS induces ED via several mechanisms, and in particular through endothelial dysfunction in penile vessels. In a high-fat diet rabbit model of MetS, a 3-month treatment with the potent and selective FXR agonist INT-747 restores endothelium-dependent relaxation in isolated cavernous tissue, normalizing responsiveness to acetylcholine and to electrical field stimulation. Accordingly, eNOS expression in the penis is greatly up-regulated by INT-747 treatment. Experiments in a rat model of chemically-induced type 1 diabetes further demonstrate that INT-747 treatment preserves erectile function induced by electrical stimulation of the cavernous nerve. These results add a new facet to the pleiotropic activities mediated by FXR, and reveal novel beneficial effects of FXR activation with potential clinical relevance. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.
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PMID:Farnesoid X receptor activation improves erectile dysfunction in models of metabolic syndrome and diabetes. 2105 55