Hiroshi Nojiri

Rapid Desensitization of Lipolysis in the Visceral and Subcutaneous Adipocytes of Rats

In adipocytes, short and long term stimulation of β adrenergic receptors (βAR) induces the desensitization to catecholamines, leading to a decrease in the intracellular accumulation of cAMP, but the roles played by this in lipolysis is not clear. In this study, we assessed the catecholamine-induced desensitization of lipolysis and compared this in adipocytes isolated from visceral and subcutaneous fat tissues of rats. When adipocytes were pretreated with isoproterenol (ISO), the norepinephrine (NE)-induced lipolysis was significantly reduced dose- and time-dependently. A similar reduction of the lipolytic response was also found in NE-, dobutamine-, terbutaline- or BRL37344-induced lipolysis. The ISO- and each βAR agonist-induced lipolysis in the visceral fat was not only higher than in the subcutaneous fat, but also markedly reduced by ISO- or NE-pretreatment. These results showed that short-term treatment of three subtypes of βAR by each agonist induces a rapid reduction in the lipolytic response to βAR stimulation. This suggests some common mechanism for the rapid desensitization of βAR-agonist-induced lipolysis, in contrast with previous reports on the characteristics of βAR subtypes. In addition, the regional difference of adipose tissue not only in inducing lipolysis but also in rapid desensitization was also apparent.

Enhancement of lipolytic responsiveness of adipocytes by novel plant extract in rat.

Subcutaneous adipocytes accumulate excess energy as triglycerides, but lipolytic response is less sensitive to catecholamines than visceral adipocytes. Obesity also induces catecholamine resistance of adipocytes. We have searched for crude drugs that could enhance the lipolytic response to noradrenalin. In this study, the lipolysis-promoting activities and action mechanisms of a novel plant extract from Hemerocallis fulva (HE) were investigated in isolated adipocytes from rat subcutaneous fat. HE exhibited no lipolysis-promoting activity alone but markedly promoted lipolysis when combined with noradrenaline; however, this synergistic activity was accompanied by no increase of intracellular cAMP production. This activity of HE was also observed when combined with cAMP analogue and was further enhanced by phosphodiesterase inhibitor. PKA inhibitor could reduce these activities of HE. These results indicate that HE is a novel lipolysis-promoting material that can sensitize the lipolytic response of adipocytes to catecholamine and suggest that HE can amplify the intra-cellular signaling pathway related to PKA or modify the other mechanism-regulating lipase activity. This characteristic material could contribute to improvement of adipose mobility in obesity-related disorder or in subcutaneous adiposity and to suppression of body fat accumulation.

Amelioration of lactic acid sensations in sensitive skin by stimulating the barrier function and improving the ceramide profile

We determined whether compensating ceramides in the stratum corneum (SC) may ameliorate the impaired barrier function and subsequently attenuate the enhanced skin sensitivity. Treatment for 4 weeks with the ceramide complex cream or the placebo cream significantly ameliorated the intensity of lactic acid sensations in 39 female subjects with sensitive skin, the degree of which was attenuated to a greater extent at 1 week by the ceramide complex cream compared with the placebo cream. The amelioration of skin sensations was accompanied by a significant increase in total ceramide content in the SC elicited by the ceramide complex cream that was significantly more effective than the placebo cream at 4 weeks. Consistently, TEWL and conductance values were significantly decreased or increased at 1 and 4 weeks, respectively, to a greater extent by the ceramide complex cream than by the placebo cream. TEWL levels were significantly correlated with the increased levels of SC total ceramide in the ceramide complex cream-treated skin but not in the placebo cream-treated skin. Thus, the amelioration of lactic acid sensations by topical application of a ceramide complex cream, provides a deep insight into the pathophysiology of sensitive skin as a reduced barrier function-dependent sub-clinical sensory response.