**4.3 Sdf2l1 modulates ER stress response and metabolism**

We then assessed the physiological and pathophysiological roles of Sdf2l1 *in vivo*. Adenovirus-mediated knocking down and knocking out of Sdf2l1 specifically in the liver of adult mice both result in enhanced ER stress during refeeding, impaired insulin signaling in the liver, systemic insulin resistance, glucose intolerance, and markedly increased triglyceride contents in the liver.

Thus, impaired induction of Sdf2l1 results in sustained ER stress, leading to insulin resistance and increased triglyceride contents, even with a normal-chow diet, indicating that dysregulation of ER stress by suppression of Sdf2l1 is a causal factor of metabolic disorders. Together with the previous reports showing that ablation of key molecules in ER stress response links impaired glucose and lipid metabolism in mice fed on a high-fat diet or a high-fructose diet [17, 21, 22], our data strongly suggest that an appropriate transient response to ER stress is induced physiologically during feeding, or eating, and terminated by Sdf2l1, and that this process may be important for the maintenance of nutrient homeostasis [33].
