Free fatty acids normalize a rosiglitazone-induced visfatin release

Area of Science:

• Endocrinology
• Metabolic Syndrome
• Pharmacology

Background:

• Elevated free fatty acids (FFAs) impair insulin sensitivity in type 2 diabetes mellitus.
• Thiazolidinediones (TZDs) are known to improve insulin sensitivity.
• The impact of TZDs on visfatin release, an insulin-mimetic adipocytokine, remains unclear.

Purpose of the Study:

• To investigate the effect of TZD treatment and FFA levels on circulating visfatin concentrations.
• To explore the in vitro regulation of visfatin release by rosiglitazone and fatty acids in human adipocytes.

Main Methods:

• A randomized, double-blind, placebo-controlled study in 16 healthy volunteers treated with rosiglitazone or placebo.
• Plasma FFA levels were elevated using triglyceride/heparin infusion.
• In vitro experiments involved incubating human adipocytes with synthetic fatty acids and rosiglitazone.

Main Results:

• Rosiglitazone treatment significantly increased plasma visfatin concentrations.
• Elevated plasma FFAs did not affect visfatin in controls but normalized it in rosiglitazone-treated subjects.
• In vitro, rosiglitazone stimulated visfatin release, which was inhibited by fatty acids and PI3K/Akt pathway inhibitors.

Conclusions:

• Visfatin release stimulated by TZDs may be a key mechanism for their metabolic effects.
• Free fatty acids antagonize TZD-induced visfatin release, potentially affecting visfatin's bioactivity.
• These findings offer insights into the complex interplay between FFAs, TZDs, and visfatin in metabolic regulation.