A research team led by Dr. LE Yingying, from the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences (INS), Shanghai Institutes for Biological Sciences, CAS, has found that TLR4 plays a critical role in glucose and lipid metabolism during fasting, and identify a novel physiological role for TLR4 in fuel homeostasis.

Mammals have evolved complex metabolic systems to adapt to food deprivation. However, the molecular basis for these adaptations has not been completely understood. In this study, Pang and colleagues investigated the involvement of TLR4 in fasting metabolism. Mice lacking TLR4 displayed aggravated fasting hypoglycemia, along with reversed activity of pyruvate dehydrogenase complex (PDC) in skeletal muscle, which might account for the fasting hypoglycemia. TLR4-/- mice also exhibited higher lipid levels in circulation and skeletal muscle after fasting, and reversed expression of lipogenic enzymes in skeletal muscle but not liver and adipose tissue. Inhibition of fatty acid synthesis in TLR4-/- mice abolished hyperlipidemia, hypoglycemia and PDC activity increase, suggesting that TLR4-dependent inhibition of muscle lipogenesis may contribute to glucose and lipid homeostasis during fasting.

This research entitled “Regulation of fasting fuel metabolism by Toll-like receptor 4” was published in Diabetes on September 20, 2010.

Other contributors in this work are graduate students PANG Shanshan and Dr. ZANG Ying Q. from INS.

AUTHOR CONTACT:
LE Yingying
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Phone: 86.21.5492.0901; Fax: 86.21.5492. 0901; E-mail: yyle@sibs.ac.cn