The discovery of dietary lipids as ligands for some of the nuclear receptors has provided a unique opportunity to study metabolic regulation at the transcriptional level and a molecular basis for developing drugs to treat metabolic diseases. Agonists of PPARs have already been used to control levels of circulating lipids and insulin sensitivity. Other potential therapeutic benefits include weight loss, increased HDL-c, and suppression of inflammation. LXR and FXR are novel targets to modulate blood cholesterol and glucose homeostasis. Other orphan receptors such as estrogen receptor-related receptors (ERRs), which regulate oxidative phosphorylation in muscle and whose activities can be modulated by synthetic compounds, also show promise in treating metabolic diseases. Recently, the NURR subfamily has been shown to play an important role in the hepatic glucogenic path-way.137 Although no ligand has been found for members of this subfamily, their expression is under the control of hormonal regulation. Lastly, about half of the nuclear receptor family members still lack endogenous or synthetic agonists. There is no doubt that the continuation of ligand search combined with studies in knockout mice will lead to discoveries of new roles for the receptors in metabolism and likely many other important biological processes.

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