title: Central nervous system lipocalin-type prostaglandin D2-synthase is correlated with orexigenic neuropeptides, visceral adiposity and markers of the hypothalamic-pituitary-adrenal axis in obese humans.
abstract: Lipocalin-type prostaglandin D2-synthase (L-PGDS) is the main producer of prostaglandin D2 (PGD2) in the central nervous system (CNS). Animal data suggest effects of central nervous L-PGDS in the regulation of food intake and obesity. No human data are available. We hypothesised that a role for CNS L-PGDS in metabolic function in humans would be reflected by correlations with known orexigenic neuropeptides. Cerebrospinal fluid (CSF) and serum samples were retrieved from 26 subjects in a weight loss study, comprising a 3-week dietary lead-in followed by 12-weeks of leptin or placebo treatment. At baseline, CSF L-PGDS was positively correlated with neuropeptide Y (NPY) (ρ = 0.695, P < 0.001, n = 26) and galanin (ρ = 0.651, P < 0.001) as well as visceral adipose tissue (ρ = 0.415, P = 0.035). Furthermore, CSF L-PGDS was inversely correlated with CSF leptin (ρ = -0.529, P = 0.005) and tended to correlate inversely with s.c. adipose tissue (ρ = -0.346, P = 0.084). As reported earlier, leptin treatment had no effect on weight loss and did not affect CSF L-PGDS or NPY levels compared to placebo. After weight loss, the change of CSF L-PGDS was significantly correlated with the change of CSF NPY levels (ρ = 0.604, P = 0.004, n = 21). Because of the correlation between baseline CSF L-PGDS levels and visceral adipose tissue, we examined associations with hypothalamic-pituitary-adrenal (HPA) axis components. Baseline CSF L-PGDS was correlated with corticotrophin-releasing hormone (ρ = 0.764, P < 0.001) and β-endorphin (ρ = 0.491, P < 0.001). By contrast, serum L-PGDS was not correlated with any of the measured variables either at baseline or after treatment. In summary, CSF L-PGDS was correlated with orexigenic neuropeptides, visceral fat distribution and central HPA axis mediators. The importance of these findings is unclear but could suggest a role for CSF L-PGDS in the regulation of visceral obesity by interaction with the neuroendocrine circuits regulating appetite and fat distribution. Further interventional studies will be needed to characterise these interactions in more detail.
authors: Department of Gastrosurgical Research and Education, Sahlgrenska Academy at Sahlgrenska University Hospital, University of Gothenburg, Sweden.
authors: E
authors: E
authors: Elias
authors: A
authors: A
authors: Benrick
authors: C J
authors: CJ
authors: Behre
authors: R
authors: R
authors: Ekman
authors: H
authors: H
authors: Zetterberg
authors: K
authors: K
authors: Stenlöf
authors: V
authors: V
authors: Wallenius
mesh_terms: D050154:Adiposity / Q000502:physiology*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002490:Central Nervous System / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000502:physiology*; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000134:cerebrospinal fluid* / Q000378:metabolism; D020738:Leptin / Q000627:therapeutic use; D054834:Lipocalins / Q000097:blood / Q000134:cerebrospinal fluid* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D009765:Obesity / Q000097:blood / Q000134:cerebrospinal fluid / Q000178:diet therapy / Q000188:drug therapy; D000068797:Orexins; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000502:physiology*; D010919:Placebos
chemical_list: D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin; D054834:Lipocalins; D009479:Neuropeptides; D000068797:Orexins; D010919:Placebos; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase