| First Author | Shimobayashi M | Year | 2018 |
| Journal | J Clin Invest | Volume | 128 |
| Issue | 4 | Pages | 1538-1550 |
| PubMed ID | 29528335 | Mgi Jnum | J:261176 |
| Mgi Id | MGI:6154492 | Doi | 10.1172/JCI96139 |
| Citation | Shimobayashi M, et al. (2018) Insulin resistance causes inflammation in adipose tissue. J Clin Invest 128(4):1538-1550 |
| abstractText | Obesity is a major risk factor for insulin resistance and type 2 diabetes. In adipose tissue, obesity-mediated insulin resistance correlates with the accumulation of proinflammatory macrophages and inflammation. However, the causal relationship of these events is unclear. Here, we report that obesity-induced insulin resistance in mice precedes macrophage accumulation and inflammation in adipose tissue. Using a mouse model that combines genetically induced, adipose-specific insulin resistance (mTORC2-knockout) and diet-induced obesity, we found that insulin resistance causes local accumulation of proinflammatory macrophages. Mechanistically, insulin resistance in adipocytes results in production of the chemokine monocyte chemoattractant protein 1 (MCP1), which recruits monocytes and activates proinflammatory macrophages. Finally, insulin resistance (high homeostatic model assessment of insulin resistance [HOMA-IR]) correlated with reduced insulin/mTORC2 signaling and elevated MCP1 production in visceral adipose tissue from obese human subjects. Our findings suggest that insulin resistance in adipose tissue leads to inflammation rather than vice versa. |
