Regulation of adipokine production in human adipose tissue by propionic acid.
BACKGROUND
Dietary fibre (DF) has been shown to be protective for the development of obesity, insulin resistance and type 2 diabetes. Short-chain fatty acids, produced by colonic fermentation of DF might mediate this beneficial effect. Adipose tissue plays a key role in the regulation of energy homeostasis, therefore, we investigated the influence of the short-chain fatty acid propionic acid (PA) on leptin, adiponectin and resistin production by human omental (OAT) and subcutaneous adipose tissue (SAT). As PA has been shown to be a ligand for G-protein coupled receptor (GPCR) 41 and 43, we investigated the role of GPCR's in PA signalling.


METHODS
Human OAT and SAT explants were obtained from gynaecological patients who underwent surgery. Explants were incubated for 24 h with PA. Adipokine secretion and mRNA expression were determined using ELISA and RT-PCR respectively.


RESULTS
We found that PA significantly stimulated leptin mRNA expression and secretion by OAT and SAT, whereas it had no effect on adiponectin. Furthermore, PA reduced resistin mRNA expression. Leptin induction, but not resistin reduction, was abolished by inhibition of Gi/o-coupled GPCR signalling. Moreover, GPCR41 and GPCR43 mRNA levels were considerably higher in SAT than in OAT.


CONCLUSIONS
We demonstrate that PA stimulates expression of the anorexigenic hormone leptin and reduces the pro-inflammatory factor resistin in human adipose tissue depots. This suggests that PA is involved in regulation of human energy metabolism and inflammation and in this way may influence the development of obesity and type 2 diabetes.
Al-Lahham
Sa'ad H
SH
Top Institute Food and Nutrition, Wageningen, The Netherlands. s.lahham@med.umcg.nl
Roelofsen
Han
H
Priebe
Marion
M
Weening
Desiree
D
Dijkstra
Martijn
M
Hoek
Annemieke
A
Rezaee
Farhad
F
Venema
Koen
K
Vonk
Roel J
RJ
D054392:Adipokines / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D011422:Propionates / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054392:Adipokines; D011422:Propionates; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C029658:propionic acid