| First Author | Sakamoto T | Year | 2016 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 310 |
| Issue | 8 | Pages | E676-E687 |
| PubMed ID | 26884382 | Mgi Jnum | J:237316 |
| Mgi Id | MGI:5811974 | Doi | 10.1152/ajpendo.00028.2015 |
| Citation | Sakamoto T, et al. (2016) Macrophage infiltration into obese adipose tissues suppresses the induction of UCP1 level in mice. Am J Physiol Endocrinol Metab 310(8):E676-E687 |
| abstractText | Emergence 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 Mvarphi) suppress the induction of thermogenic adipocytes 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 Mvarphi infiltrated. Depletion of M1 Mvarphi using clodronate liposomes eliminated the suppressive effect and markedly reduced the mRNA level of tumor necrosis factor-alpha (TNFalpha) 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 TNFalpha protein suppressed UCP1 induction in lean adipose tissues of mice. Collectively, our data indicate that infiltrated M1 Mvarphi suppress the induction of thermogenic adipocytes in obese adipose tissues via TNFalpha. This report suggests that inflammation induced by infiltrated Mvarphi could cause not only insulin resistance but also reduction of energy expenditure in adipose tissues. |
