Adipose tissue remodeling

作者：Ogawa Yoshihiro^*

来源：Journal of the Pharmaceutical Society of Japan, 2007, 127: 13-14.

• adipocytes
• macrophages
• free fatty acids
• TNF alpha

Obese adipose tissue is characterized by adipocyte hypertrophy, neoanglogenesis, macrophage infiltration, and imbalance between pro-inflammatory and anti-inflammatory adipocytokines, suggesting the previously unrecognized dynamic changes, which may be referred to as "adipose tissue remodeling". Using an in vitro co-culture system composed of adipocytes and macrophages, we have demonstrated that a paracrine loop involving saturated fatty acids and TNF alpha derived from adipocytes and macrophages, respectively, establishes a vicious cycle that aggravates I. inflammatory changes" saturated fatty acids, which are released in large quantities from hypertrophied adipocytes via the macrophage-induced adipocyte lipolysis, serve as a naturally occurring ligand for TLR4 to Induce NF-kappa B activation. We have also observed the attenuation of obesity-induced adipose tissue inflammation in C3H/HeJ mice carrying a TLR4 mutation relative to control C3H/HeN mice. Very recently, we have demonstrated that highly purified EPA, the only class of n-3 polyunsaturated fatty acids that has been used clinically to treat hyperlipidemia and has proved to reduce the risk of major coronary events in a large-scale, prospective, randomized clinical trial, increases tile secretion of an anti-inflammatory adipocytokine adiponectin in rodent models of obesity and human obese subjects. Importantly, EPA reverses the co-culture-induced decrease in adiponectin secretion at least In part through down-regulation of TNFa in macrophages. Our data help unveil the molecular mechanism underlying "adipose tissue remodeling" and identify the therapeutic targets that may reduce obesity-induced inflammation and thus the metabolic syndrome associated with excess adiposity.

• 出版日期2007