bims-exemet 2021-09-19 papers

Issue of 2021–09–19
two papers selected by
Javier Botella Ruiz, Victoria University

Endocr J. 2021 Sep 11.

Elucidating exercise-induced skeletal muscle signaling pathways and applying relevant findings to preemptive therapy for lifestyle-related diseases.

Masato Iwabu, Miki Okada-Iwabu, Takashi Kadowaki, Toshimasa Yamauchi.

While it is well recognized that exercise represents a radical preventive and therapeutic measure for lifestyle-related diseases, it is clear that contemporary lifestyles abound with situations where exercise may be found difficult to implement on a continuous basis. Indeed, this has led to global expectations for elucidation of the exercise-activated skeletal muscle signaling pathways as well as for development of exercise mimics that effectively activate such pathways. It is shown that exercise activates the transcriptional coactivator PGC-1α via AMPK/SIRT1 in muscle, thereby not only enhancing mitochondrial function and muscle endurance but upregulating energy metabolism. Further, adipocyte-derived adiponectin is also shown to activate AMPK/SIRT1/PGC-1α via its receptor AdipoR1 in skeletal muscles. Thus, adiponectin/AdipoR1 signaling is thought to constitute exercise-mimicking signaling. Indeed, it has become clear that AMPK, SIRT1 and AdipoR activators act as exercise mimetics. With the crystal structures of AdipoR elucidated and humanized AdipoR mice generated toward optimization of candidate AdipoR-activators for human use, expectations are mounting for the clinical application in the near future of AdipoR activators as exercise mimetics in humans. This review provides an overview of molecules activated by exercise and compounds activating these molecules, with a focus on the therapeutic potential of AdipoR activators as exercise mimetics.

Keywords: AdipoR; AdipoR activators; Exercise mimetics

DOI: https://doi.org/10.1507/endocrj.EJ21-0294

Diabetologia. 2021 Sep 12.

Sitting less elicits metabolic responses similar to exercise and enhances insulin sensitivity in postmenopausal women.

Carlijn M E Remie, Georges E Janssens, Lena Bilet, Michel van Weeghel, Bernard M F M Duvivier, Vera H W de Wit, Niels J Connell, Johanna A Jörgensen, Bauke V Schomakers, Vera B Schrauwen-Hinderling, Joris Hoeks, Matthijs K C Hesselink, Esther Phielix, Riekelt H Houtkooper, Patrick Schrauwen.

AIMS/HYPOTHESIS: In our current society sedentary behaviour predominates in most people and is associated with the risk of developing type 2 diabetes. It has been suggested that replacing sitting time by standing and walking could be beneficial for individuals with type 2 diabetes but the underlying mechanisms are unknown and direct comparisons with exercise are lacking. Our objective was to directly compare metabolic responses of either sitting less or exercising, relative to being sedentary.
METHODS: We performed a randomised, crossover intervention study in 12 overweight women who performed three well-controlled 4 day activity regimens: (1) sitting regimen (sitting 14 h/day); (2) exercise regimen (sitting 13 h/day, exercise 1 h/day); and (3) sitting less regimen (sitting 9 h/day, standing 4 h/day and walking 3 h/day). The primary outcome was insulin sensitivity measured by a two-step hyperinsulinaemic-euglycaemic clamp. We additionally performed metabolomics on muscle biopsies taken before the clamp to identify changes at the molecular level.
RESULTS: Replacing sitting time by standing and walking over 4 days resulted in improved peripheral insulin sensitivity, comparable with the improvement achieved by moderate-to-vigorous exercise. Specifically, we report a significant improvement in peripheral insulin sensitivity in the sitting less (~13%) and the exercise regimen (~20%), compared with the sitting regimen. Furthermore, sitting less shifted the underlying muscle metabolome towards that seen with moderate-to-vigorous exercise, compared with the sitting regimen.
CONCLUSIONS/INTERPRETATIONS: Replacing sitting time by standing and walking is an attractive alternative to moderate-to-vigorous exercise for improving metabolic health.
TRIAL REGISTRATION: ClinicalTrials.gov NCT03912922.

Keywords: Clinical trial; Exercise; Insulin sensitivity; Metabolomics; Muscle metabolism; Sedentary time; Sitting; Sitting less

DOI: https://doi.org/10.1007/s00125-021-05558-5