Abstract-We tested the hypothesis that activation of transient receptor potential vanilloid type-1 (TRPV1) by capsaicin prevents adipogenesis. TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans were detected by immunoblotting and quantitative real-time RT-PCR. The effect of TRPV1 on cytosolic calcium was determined fluorometrically in 3T3-L1-preadipocytes and in human visceral fat tissue. Adipogenesis in stimulated 3T3-L1-preadipocytes was determined by oil red O-staining of intracellular lipid droplets, triglyceride levels, expression of peroxisome proliferator-activated receptor-␥, and expression of fatty acid synthase. Long-term feeding experiments were undertaken in wild-type mice and TRPV1 knockout mice. We detected TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans. In vitro, the TRPV1 agonist capsaicin dose-dependently induced calcium influx and prevented the adipogenesis in stimulated 3T3-L1-preadipocytes. RNA interference knockdown of TRPV1 in 3T3-L1-preadipocytes attenuated capsaicin-induced calcium influx, and adipogenesis in stimulated 3T3-L1-preadipocytes was no longer prevented. During regular adipogenesis TRPV1 channels were downregulated which was accompanied by a significant and time-dependent reduction of calcium influx. Compared with lean counterparts in visceral adipose tissue from obese db/db and ob/ob mice, and from obese human male subjects we observed a reduced TRVP1 expression. The reduced TRPV1 expression in visceral adipose tissue from obese humans was accompanied by reduced capsaicin-induced calcium influx. The oral administration of capsaicin for 120 days prevented obesity in male wild type mice but not in TRPV1 knockout mice assigned to high fat diet. We conclude that the activation of TRPV1 channels by capsaicin prevented adipogenesis and obesity. Key Words: transient receptor potential vanilloid type-1 Ⅲ RNAi Ⅲ TRPV1 knockout adipogenesis Ⅲ obesity V isceral obesity as clinically assessed by waist circumference depends on the proliferation and growth of preadipocytes which is closely regulated by several genes and extracellular factors. 1-3 Among these factors capsaicin ((E)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methyl-6-nonenamide) has been shown to affect lipid metabolism and obesity. 4,5 However, the underlying mechanisms by which capsaicin affect visceral adipose tissue have not been completely clarified yet. Recent studies indicated that capsaicin activates the transient receptor potential vanilloid type-1 (TRPV1) channel. 6 -8 The capsaicin receptor TRPV1 belongs to the family of nonselective cation channels with high calcium permeability. 9 Now, we tested the hypothesis that capsaicin-induced activation of TRPV1 in preadipocytes prevents adipogenesis and obesity. We showed that the activation of TRPV1 channels by capsaicin increased cytosolic calcium and prevented adipogenesis of preadipocytes in vitro. The effects of capsaicin on adipogenesis were attenuated after TRPV1 knockdown. Furthermore, ...

BACKGROUND-Safe, accurate methods permitting simultaneous and/or repeated measurement of red blood cell (RBC) survival (RCS) are important to investigate pathophysiology and therapy of anemia. Methods using chromium 51 ( 51 Cr) -labeled RBCs are unacceptable for infants, children, and pregnant women. We report RCS measured in vivo using RBCs labeled with several densities of biotin (BioRBCs).

BACKGROUND-Anemia is a serious problem in critically ill neonates. To investigate the pathophysiology of anemia and responses to red blood cell (RBC) transfusions and erythropoietin therapy, repeated measurement of red cell volume (RCV) and blood volume are useful. To extend our previous sheep study in which RBCs were labeled at four different biotin densities, we assessed the validity of this multidensity method for in vivo measurement of circulating RCV in humans.