Abstract
Rodent experiments have emphasized a role of central fatty acid (FA) species, such as oleic acid, in regulating peripheral glucose and energy metabolism. Thus, we hypothesized that central FAs are related to peripheral glucose regulation and energy expenditure in humans. To test this we measured FA species profiles in cerebrospinal fluid (CSF) and plasma of 32 individuals who stayed in our clinical inpatient unit for 6 days. Body composition was measured by dual energy X-ray absorptiometry and glucose regulation by an oral glucose test (OGTT) followed by measurements of 24 hour (24EE) and sleep energy expenditure (SLEEP) as well as respiratory quotient (RQ) in a respiratory chamber. CSF was obtained via lumbar punctures; FA concentrations were measured by liquid chromatography/mass spectrometry. As expected, FA concentrations were higher in plasma compared to CSF. Individuals with high concentrations of CSF very-long-chain saturated FAs had lower rates of SLEEP. In the plasma moderate associations of these FAs with higher 24EE were observed. Moreover, CSF monounsaturated long-chain FA (palmitoleic and oleic acid) concentrations were associated with lower RQs and lower glucose area under the curve during the OGTT. Thus, FAs in the CSF strongly correlated with peripheral metabolic traits. These physiological parameters were most specific to long-chain monounsaturated (C16∶1, C18∶1) and very-long-chain saturated (C24∶0, C26∶0) FAs. Conclusions: Together with previous animal experiments these initial cross-sectional human data indicate that central FA species are linked to peripheral glucose and energy homeostasis.
Highlights
Recent advances in lipidomic profiling have shown that specific fatty acid (FA) species in human plasma are associated with adiposity and lifestyle variables, such as smoking, physical activity and diet, while others correlate with hepatic and whole-body insulin sensitivity [1,2,3,4]
Study Outline This is an analysis of paired plasma and cerebrospinal fluid (CSF) samples collected in our research unit during a study investigating the role of leptin in body weight regulation
Except for a-linolenic and docosahexaenoic acid (r = 0.58, P = 0.001; r = 0.48, P = 0.01, respectively), none of the measured FA species were correlated between plasma and CSF
Summary
Recent advances in lipidomic profiling have shown that specific fatty acid (FA) species in human plasma are associated with adiposity and lifestyle variables, such as smoking, physical activity and diet, while others correlate with hepatic and whole-body insulin sensitivity [1,2,3,4]. The data presented in this manuscript demonstrate that in humans FA species in the CNS stratified by chain length and degree of saturation are associated with peripheral metabolism.
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