Macrophage infiltration into obese adipose tissues suppresses the induction of UCP1 level in mice

Tomoya Sakamoto, Takahiro Nitta, Koji Maruno, Yu-Sheng Yeh, Hidetoshi Kuwata, Koichi Tomita, Tsuyoshi Goto, Nobuyuki Takahashi, Teruo Kawada
2016 American Journal of Physiology. Endocrinology and Metabolism  
gence of thermogenic adipocytes such as brown and beige adipocytes is critical for whole body energy metabolism. Promoting the emergence of these adipocytes, which increase energy expenditure, could be a viable strategy in treating obesity and its related diseases. However, little is known regarding the mechanisms that regulate the emergence of these adipocytes in obese adipose tissue. Here, we demonstrated that classically activated macrophages (M1 M) suppress the induction of thermogenic
more » ... cytes in obese adipose tissues of mice. Cold exposure significantly induced the expression levels of uncoupling protein-1 (UCP1), which is a mitochondrial protein unique in thermogenic adipocytes, in C57BL/6 mice fed a normal diet. However, UCP1 induction was significantly suppressed in adipose tissues of C57BL/6 mice fed a high-fat diet, into which M1 M infiltrated. Depletion of M1 M using clodronate liposomes eliminated the suppressive effect and markedly reduced the mRNA level of tumor necrosis factor-␣ (TNF␣) in the adipose tissues. Importantly, consistent with the observed changes in the expression levels of marker genes for thermogenic adipocytes, combination treatment of clodronate liposome and cold exposure resulted in metabolic benefits such as lowered body weight and blood glucose level in obese mice. Moreover, intraperitoneal injection of recombinant TNF␣ protein suppressed UCP1 induction in lean adipose tissues of mice. Collectively, our data indicate that infiltrated M1 M suppress the induction of thermogenic adipocytes in obese adipose tissues via TNF␣. This report suggests that inflammation induced by infiltrated M could cause not only insulin resistance but also reduction of energy expenditure in adipose tissues.
doi:10.1152/ajpendo.00028.2015 pmid:26884382 fatcat:6rokblcg7vhvlmkp6l3puobgtq