AMP-activated protein kinase (AMPK) senses and maintains energy balance in peripheral tissues. When energy is deficient, AMPK activation leads to altered cellular metabolism and gene expression to inhibit anabolic processes, stimulate catabolism, and restore ATP. The CNS integrates diverse central and peripheral signals to maintain homeostasis. CNS AMPK is shown to have important, but complex roles in energy balance. CNS neurons sense their own energy needs, while some also integrate neuro-humoral signals to assess organismal energy balance. In the brain, AMPK is involved in both arenas, coordinating context-specific metabolic responses in many tissues. AMPK plays roles in both physiological (feeding) and pathophysiological (ischemic) states. During the latter, AMPK is highly activated to restore neuronal energy balance, but its over-activation may be deleterious. In this study, we review AMPK regulation and responses to cellular and organismal energy challenges in the CNS. AMP-activated protein kinaseAMP-activated protein kinase is a serine/threonine kinase with a catalytic a subunit and regulatory b and c subunits. AMPK not only senses energy status, but also functions at the tissue and organism levels to promote context-specific responses to physiological signals of metabolic status. AMPK modulates many aspects of cellular metabolism (Fig. 1a). AMPK was first known to be activated by ATP depletion (increased AMP/ATP ratio) and related stimuli (exercise, starvation, hypoxia, cellular pH and redox status, increased creatine/phosphocreatine ratio). However, AMPK is also activated by certain drugs, hormones, and cellular stressors that do not alter AMP/ATP ratio.

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The 5 -adenosine monophosphate-activated protein kinase (AMPK) is a metabolic and stress sensor that has been functionally conserved throughout eukaryotic evolution. Activation of the AMPK system by various physiological or pathological stimuli that deplete cellular energy levels promotes activation of energy restorative processes and inhibits energy consumptive processes. AMPK has a prominent role not only as a peripheral sensor of energy balance, but also in the CNS as a multifunctional metabolic sensor. Recent work suggests that AMPK plays an important role in maintaining whole body energy balance by coordinating feeding behaviour through the hypothalamus in conjunction with peripheral energy expenditure. In addition, brain AMPK is activated by energy-poor conditions induced by hypoxia, starvation, and ischaemic stroke. Under these conditions, AMPK is activated as a protective response in an attempt to restore cellular homeostasis. However in vivo, it appears that the overall consequence of activation of AMPK is more complex than previously imagined, in that over-activation may be deleterious rather than neuroprotective. This review discusses recent findings that support the role of AMPK in brain as a multidimensional energy sensor and the consequences of its activation or inhibition under physiological and pathological states.

Background: CTRP4 is a conserved member of the C1q family of secreted proteins with poorly defined function. Results: CTRP4 acts in the hypothalamus to modulate food intake and body weight by regulating the expression of orexigenic neuropeptide expression. Conclusion: CTRP4 plays a role in food intake regulation. Significance: This study establishes the first known in vivo function of CTRP4.