Adipocytes niacin

While the precise mechanism regarding the pharmacological action of niacin remains elusive, it is known that niacin binds to GPR109A on adipocytes and decreases the hydrolysis of adipocyte TG, thereby resulting in a... 

Thus GPR109A mediates the niacin-induced antilipolysis effect in adipocytes and vasodilation effect in skin. This discovery represents significant progress in understanding the mechanism of action for niacin, but also poses a challenge to develop a therapeutic agent to separate the lipid and vasodilation effects. 

Linke, A., Sonnabend, M., Fasshauer, M., Hollriegel, R., Schuler, G., Nie-bauer, J., Stumvoll, M., and Bluher, M., 2009. Effects of extended-release niacin on lipid profile and adipocyte biology in patients with impaired glucose tolerance. Atherosclerosis. 205 207-213. 

Role of the Niacin Receptor (GPR109A) in Inhibiting Non-esterifled Fatty Acid Release from Adipocytes... 

The first hypotheses for cholesterol reduction with niacin pointed toward a steep niacin-induced decrease in non-esterified fatty acid (NEFA) mobilization from adipose tissue via inhibition of lipolysis (reviewed by Carlson 2005). Hormone sensitive lipase mediates lipolysis in response to increased cyclic adenosine monophosphate in adipocytes. A G-protein-coupled cell surface receptor (GPR) inhibiting adenylyl cyclase was proposed, and in 2003, three independent groups identified the human niacin receptors as the low-affinity... 

Figure 39.1 Pharmacological effects of niacin relevant to atherosclerosis. Effects on adipocytes and dermal Langerhans cells—and probably effects on macrophages—are dependent on a G-protein coupled receptor, GPR 109A. The liver, which mediates most of the changes in lipoprotein metabolism, does not express this receptor. Effects demonstrated in endothelial cells are not known to be receptor-dependent.

Marked inhibition by niacin of triglyceride lipolysis in adipocytes is mediated by the G-protein-coupled receptor, GPR109A. 

Cardiovascular event reductions occurred in randomized trials using twice-daily mealtime niacin, but not in a recent trial of niacin administered at bedtime with minimal or no food intake. This raises the possibility that niacin s effect of blocking the normal fuel supply of fatty acids released from adipocytes might have adverse consequences that restrict the ability of bedtime niacin to reduce cardiovascular events. 

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