Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2010) 21 P179

SFEBES2009 Poster Presentations Diabetes and metabolism (59 abstracts)

Functional muscarinic acetylcholine receptors are expressed in white and brown adipose tissue

Mark Stephens , Aled Rees & Marian Ludgate


University Hospital of Wales, Cardiff, UK


Both brown (BAT) and white (WAT) adipose tissue have neuroanatomically well characterized sympathetic innervation (with activation initiating lipid mobilization), but little evidence to support the presence of a (putatively counter-regulatory) parasympathetic input.

Parasympathetic actions are mediated through muscarinic acetylcholine receptors (mAChR). The mouse 3T3-L1 (white fat-derived) cell line expresses M1, M3 and M4 mAChR during differentiation; there was no evidence of either M2 or M5 mAChR. M4 mRNA transcripts are present in the greatest concentrations (up to 7.43/1000ARP, compared with 0.54/1000ARP (M1) and 0.24/1000ARP (M3) in 3T3-L1 cells). M3 expression increases significantly during adipogenesis, whilst M1 and M4 exhibited little variation with time. Western blot analysis confirms the presence of mAChR protein.

Incubation of 3T3-L1 cells with carbachol, a non-specific cholinergic agonist, produces a variable enhancement of GPDH (a terminal marker of adipogenesis) mRNA expression in the differentiating adipocytes. This is abolished by the addition of the universal muscarinic antagonist, atropine. Pirenzepine and P-fluorohexahydrosila-difenadiol, specific M1 and M3 antagonists respectively, significantly reduce GPDH transcripts in the presence of carbachol; these effects appear additive when the two are combined. Incubation with tropicamide (an M4 antagonist) has no effect on GPDH expression.

GPDH expression (percentage of control cells in adipogenic medium; mean±S.E.M.)P value (n)
Carbachol (1 μM)142.4±27.6NS (9)
Carbachol and antagonists
Atropine (1 mM)70.5±17.50.048 (3)
Pirenzepine (10 nM)51.4±6.30.0067 (3)
P-Fluorohexahydrosila- difenadiol (1 μM)66.1±5.60.018 (3)
Pirenzepine and P-fluoro- hexahydrosila-difenadiol23.6±13.10.0016 (3)
Tropicamide (10 μM)105.5±17.5NS (3)

The antagonists have no significant effect on GPDH levels in the absence of carbachol.

Primary cultures of mouse and human BAT and WAT express M1, M3 and M4 mAChR at levels comparable to 3T3-L1 cells, validating their use as a model system. Our results suggest the possibility of direct end-organ parasympathetic modulation of fat metabolism, and may represent a novel therapeutic target in obesity.

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