1: Worksite-based intensive lifestyle therapy has profound cardiometabolic benefits in people with obesity and type 2 diabetes.
Science of the Month - October 2022
Cell Metabolism.
2022 Sep 2;S1550-4131(22)00355-2. doi: 10.1016/j.cmet.2022.08.012.
Mihoko Yoshino, Jun Yoshino, Gordon I. Smith, Richard I. Stein, Adam J. Bittel, Daniel C. Bittel, Dominic N. Reeds, David R. Sinacore, W. Todd Cade, Bruce W. Patterson, Kevin Cho, Gary J. Patti, Bettina Mittendorfer, Samuel Klein
Lifestyle therapy centered on diet and exercise is the foundation of type 2 diabetes treatment, but its implementation is not easy. In this study, we conducted a randomized controlled trial on employees with obesity and type 2 diabetes at Washington University in the U.S. to examine the effects of an eight-month intensive lifestyle therapy program in the "workplace" on cardiometabolic function and its underlying mechanisms. The worksite-based lifestyle therapy (diet and exercise) achieved high compliance and demonstrated significant therapeutic effects for diabetes, including remarkable weight loss (17%), improved body composition (weight loss while maintaining muscle mass), and increased cardiorespiratory fitness and muscle strength, compared to standard lifestyle guidance and medical intervention. Furthermore, as for the underlying mechanism, it was suggested that the enhancement of mitochondrial function through the activation of the NAMPT-mediated NAD+ synthesis pathway and sirtuin signaling in skeletal muscle was involved. These findings strongly suggest that worksite-based lifestyle therapy has extremely effective therapeutic benefits for obesity and type 2 diabetes. We recognize that these excellent therapeutic effects are not limited to the workplace and can be achieved if an environment is created that maintains patient motivation and ensures high compliance. We hope to expand these activities in Japan.
(Mihoko Yoshino, Keio Global Research Institute, equivalent to the class of 1979)
2: Cell-matrix interface regulates dormancy in human colon cancer stem cells. Nature. 2022 Aug;608(7924):784-794. doi: 10.1038/s41586-022-05043-y.
Nature.
2022 Aug;608(7924):784-794. doi: 10.1038/s41586-022-05043-y.
Ohta Y, Fujii M, Takahashi S, Takano A, Nanki K, Matano M, Hanyu H, Saito M, Shimokawa M, Nishikori S, Hatano Y, Ishii R, Sawada K, Machinaga A, Ikeda W, Imamura T, Sato T.
Cancer stem cells, which possess both self-renewal and tumor-repopulating abilities, have been considered to play a crucial role in chemotherapy resistance and recurrence, which are obstacles to a complete cure for cancer. However, conventional research methods could only provide snapshot information of tissues at a single point in time, leaving it unclear how cancer stem cells actually behave before and after chemotherapy. Therefore, in this study, with the cooperation of Professor Imamura of Ehime University, we built an in vivo live imaging system within the JKiC facility and developed a technology to observe individual human cancer cells in a living state. Using this system to observe the behavior of cancer stem cells in detail, we captured how some colon cancer stem cells survive after chemotherapy by maintaining a "dormant state" and then resume proliferation to repopulate the tumor. Furthermore, by investigating the mechanism that governs the switch between dormancy and proliferation in cancer stem cells, we revealed that the adhesion signal between the cell and the basement membrane, mediated by COL17A1, plays a crucial role. Dormant cancer stem cells maintain their dormant state by strongly adhering to the basement membrane, but when COL17A1 is destroyed by chemotherapy, the FAK-YAP signal is activated, and they resume proliferation. Focusing on the fact that this YAP signal is essential for the resumption of proliferation in dormant cancer stem cells, we demonstrated in animal models that tumor recurrence can be prevented with a next-generation YAP signal inhibitor (TEAD inhibitor). This achievement is expected to lead to the development of therapies from the new perspective of preventing tumor recurrence after chemotherapy.
(Toshiro Sato, Department of Organoid Medical Sciences, The Sakaguchi Laboratory, class of 1976)
Other Published Papers
1: A combined stem-cell-gene therapy strategy for ALS.
Okano H.
2: Maiden voyage: Induced pluripotent stem cell-based drug screening for amyotrophic lateral sclerosis.
Brain.
2022 Aug 25;awac306. doi: 10.1093/brain/awac306.
Daisuke Ito, Satoru Morimoto, Shinichi Takahashi, Kensuke Okada, Jin Nakahara, Hideyuki Okano