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Nuclear receptors integrate hormonal and nutritional signals, resulting in changes to key metabolic pathways within the body. The liver X receptor (LXR) and the farnesoid X receptor (FXR), which are activated by oxysterols and bile acids, respectively, have essential roles in the regulation of cholesterol and bile acid metabolism but are also key integrators of sterol, fatty acid and glucose metabolism.
Sirtuins are a family of deacetylases that target histones and proteins in several cellular compartments. Sirtuins are crucial regulators of energy homeostasis, as they detect physiological changes in energy levels and modulate glucose and lipid metabolism accordingly. As such, they affect health in a pleiotropic manner.
MicroRNAs (miRNAs) have recently emerged as key regulators of metabolism. For example, miR-33a and miR-33b control cholesterol and lipid metabolism in concert with their host genes, the sterol-regulatory element-binding protein (SREBP) transcription factors. miRNAs also regulate insulin and glucose homeostasis. Thus, miRNAs may be potential therapeutic targets for ameliorating cardiometabolic disorders.
AMPK acts as an intracellular energy sensor, as its activity is tuned by the relative levels of ATP, ADP and AMP. Therefore, it has a central role in the regulation of cellular metabolic pathways and in the control of whole-body energy balance.
Metabolomics enables the comprehensive profiling of cellular metabolites at the systems level, thereby providing a direct readout of biochemical activity that can be correlated with phenotype and used to identify therapeutic targets. Although several challenges remain to be addressed, emerging mass spectrometric and bioinformatic technologies have already proven to be effective tools for diagnostics and for providing insights into cell metabolism.
Signalling is known to regulate metabolism, and it is becoming clear that this regulation is reciprocal, with signalling pathways being regulated by the availability of nutrient-sensitive modifications, such as acetylation and glycosylation. This tight link between signalling and metabolism allows cells to modulate their activities according to metabolic status.
