**5. Conclusions**

We reveal that eating induces physiological and transient ER stress and ER stress response, including up-regulation of Sdf2l1, in the liver. In obesity and diabetes, however, ER stress response failure, including down-regulation of Sdf2l1, results in sustained ER stress, which links insulin resistance and the development of steatohepatitis comorbid with diabetes.

## **Acknowledgements**

We thank the co-workers, especially Dr. Naoto Kubota (The University of Tokyo), Prof. Kazuyuki Tobe (The University of Toyama), Prof. Kazuhiko Koike (The University of Tokyo), and Prof. Takashi Kadowaki (The University of Tokyo; Toranomon Hospital).
