If PAR2 is involved in the airway host defense system, future research should focus on the potential of this receptor as a target for therapeutic intervention. Cirrhosis represents the end-stage of any chronic liver disease, characterized by the most advanced stage of fibrosis, distortion of the liver parenchyma associated with septae and nodule formation, altered blood flow and the potential development of liver failure at long term. The author concludes that the brain is MK-2206 2HCl autonomous in producing most lipids. However, others have postulated that FAs enter the brain from the blood. Nevertheless, brain fatty acid uptake from the periphery at physiological levels still awaits final proof and therefore the interpretation of our findings is additionally limited. One reason for the lack of associations of FAs between the peripheral and the central compartment in our study could be that by far the largest portion of plasma FAs are bound to plasma proteins, such as albumin, which could have blunted associations between the respective FA species. Another potential issue which could account for this lack of association is that plasma lipoproteins represent an additional source for FA transport across the BBB. It has been proposed that the lipoprotein lipase located on the cerebral microvessel endothelium can liberate additional FAs from lipoproteins making them available for transport into the brain. Thus, whether associations of respective FA species between the periphery and the CNS also reflect FA trafficking between the two compartments needs to be further explored and in this regard our data need to be viewed as preliminary. These data indirectly support our observation of a negative association of central abundance of arachidonic acid with GAUC. In mice, Lam et al. have demonstrated that under hyperlipidemic conditions hypothalamic sensing of FAs is required for peripheral glucose homeostasis. This occurs via coenzyme-A-esterified FAs which activate hypothalamic K+ channels and recruit vagal efferents to the liver controlling hepatic glucose production. Together, based on our results and existing literature, it may be possible that besides central oleic and palmitoleic acid, central long-chain FAs with a higher degree of desaturation may also be important candidates for central regulation of peripheral glucose utilization in humans. One limiting factor of our study is the relatively low number of study subjects. However, CSF is difficult to obtain thus limiting sample size of such studies. Furthermore, we measured FA profiles in CSF and not brain tissue. Thus, conclusions are based on the assumption that FA in CSF are linked to peripheral metabolic traits and we therefore can only speculate on brain tissue concentrations and signal transduction pathways in the brain tissue itself. It also must be acknowledged that due to the large number of measurements, lipidomic studies are subject to false discovery error due to multiple comparisons. Nevertheless, some of the associations in this analysis were robust to the conservative Bonferonni correction for multiple comparisons and at the same time consistent with data previously presented in the literature.