Exercise—A Panacea of Metabolic Dysregulation in Cancer: Physiological and Molecular Insights

Raun, Steffen H.; Buch-Larsen, Kristian; Schwarz, Peter; Sylow, Lykke

doi:10.3390/ijms22073469

Cited by 10 publications

(6 citation statements)

References 261 publications

(344 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…71 Our study shows that altered mTORC1 activity also extends to insulin-stimulated mTORC1 signaling and suggests that cancer-associated insulin resistance expands to the level of anabolism. These findings support the theory that cancer leads to muscle insulin resistance, [72][73][74] which in turn accelerates muscle loss in cancer cachexia. While atrophy of both oxidative and glycolytic muscle fibers was reported in rodent and human cancer cachexia, 75 some evidence suggests that the glycolytic type II fibers may be more prone to muscle mass loss.…”

Section: Discussionsupporting

confidence: 86%

Cancer causes dysfunctional insulin signaling and glucose transport in a muscle‐type‐specific manner

et al. 2022

Self Cite

View full text Add to dashboard Cite

Metabolic dysfunction and insulin resistance are emerging as hallmarks of cancer and cachexia, and impair cancer prognosis. Yet, the molecular mechanisms underlying impaired metabolic regulation are not fully understood. To elucidate the mechanisms behind cancer-induced insulin resistance in muscle, we isolated extensor digitorum longus (EDL) and soleus muscles from Lewis Lung Carcinoma tumor-bearing mice.Three weeks after tumor inoculation, muscles were isolated and stimulated with or without a submaximal dose of insulin (1.5 nM). Glucose transport was measured using 2-[ 3 H]Deoxy-Glucose and intramyocellular signaling was investigated using immunoblotting. In soleus muscles from tumor-bearing mice, insulin-stimulated glucose transport was abrogated concomitantly with abolished insulin-induced TBC1D4 and GSK3 phosphorylation. In EDL, glucose transport and TBC1D4 phosphorylation were not impaired in muscles from tumor-bearing mice, while AMPK signaling was elevated. Anabolic insulin signaling via phosphorylation of the mTORC1 targets, p70S6K thr389, and ribosomal-S6 ser235, were decreased by cancer in soleus muscle while increased or unaffected in EDL. In contrast, the mTOR substrate, pULK1 ser757, was reduced in both soleus and EDL by cancer. Hence, cancer causes considerable changes in skeletal muscle insulin signaling that is dependent on muscle-type, which could contribute to metabolic dysregulation in cancer. Thus, the skeletal muscle could be a target for managing metabolic dysfunction in cancer.

show abstract

Section: Discussionsupporting

confidence: 86%

Cancer causes dysfunctional insulin signaling and glucose transport in a muscle‐type‐specific manner

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our study show that altered mTORC1 activity also extends to insulin-stimulated mTORC1 signaling and suggests that cancer-associated insulin resistance extends to the level of anabolism. The current data support the theory that cancer leads to muscle insulin resistance [61][62][63] , which in turn could accelerate muscle loss in cancer cachexia. However, this has yet to be experimentally verified in preclinical models or patients.…”

Section: Discussionsupporting

confidence: 85%

Cancer causes dysfunctional insulin signaling and glucose transport in a muscle-type specific manner

Raun

Knudsen

Han

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Metabolic dysfunction and insulin resistance are emerging as hallmarks of cancer and cachexia, and impair cancer prognosis. Yet, the molecular mechanisms underlying impaired metabolic regulation is not fully understood. To elucidate the mechanisms behind cancer-induced insulin resistance in muscle, we isolated extensor digitorum longus (EDL) and soleus muscles from Lewis Lung Carcinoma tumor-bearing mice. Three weeks after tumor inoculation, muscles were isolated and stimulated with or without a submaximal dose of insulin (1.5 nM). Glucose transport was measured using 2-[3H]Deoxy-Glucose and intramyocellular signaling was investigated using immunoblotting. In soleus muscles from tumor-bearing mice, insulin-stimulated glucose transport was abrogated concomitantly with abolished insulin-induced TBC1D4 and GSK3 phosphorylation. In EDL, glucose transport and TBC1D4 phosphorylation were not impaired in muscles from tumor-bearing mice, while AMPK signaling was elevated. Anabolic insulin signaling via phosphorylation of the mTORC1 targets, p70S6K thr389 and ribosomal-S6 ser235, were decreased by cancer in soleus muscle while increased or unaffected in EDL. In contrast, the mTOR substrate, pULK1 ser757, was reduced in both soleus and EDL by cancer. Hence, cancer causes considerable changes in skeletal muscle insulin signaling that is dependent of muscle-type, which could contribute to metabolic dysregulation in cancer. Thus, skeletal muscle could be a target for managing metabolism in cancer.HighlightsCancer abrogates insulin-stimulated glucose transport selectively in oxidative soleus muscleMultiple TBC1D4 phosphorylation sites are reduced in cancer-associated muscle insulin resistanceCancer leads to increased AMPK signaling in the glycolytic EDL muscleCancer alters anabolic insulin signaling in soleus and EDL muscle

show abstract

“…Diet and exercise have been an area of increasing interest when looking at patients with BC [ 9 ]. Thus, when examining metabolism it is important to look at these aspects and for this Patient-Reported Outcomes (PROs) is often the method of choice [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Weight Change in Post-Menopausal Women with Breast Cancer during Chemotherapy—Perspectives on Nutrition, Activity and Bone Metabolism: An Interim Analysis of a 5-Year Prospective Cohort

et al. 2021

Self Cite

View full text Add to dashboard Cite

Women with breast cancer are a growing population due to improved screening and treatment. It has been described that chemotherapy can negatively affect patients’ metabolism. The aim of this study is to assess weight gain during chemotherapy treatment in an interim analysis on an ongoing prospective cohort of women with early breast cancer. To help untangle the many possible reasons for weight change, we examine blood tests, Patient-Reported Outcomes (PROs), and bone mineral density (BMD). We find that the 38 women that have measurements taken after chemotherapy have an average weight gain of 1.2 kg although not significant. Together with this, there is a significant drop in HDL cholesterol, an increase in triglycerides, and a non-significant tendency towards decreased insulin sensitivity. PROs show that although the women experience more pain and fatigue, they have higher activity levels. BMD is at an expected level according to age. All in all, we see an increased focus on physical activity and nutrition, leading to less severe metabolic changes as previously reported. However, even though more measures are taken, we still see an overall negative metabolic impact with unknown long-term implications.

show abstract

Exercise—A Panacea of Metabolic Dysregulation in Cancer: Physiological and Molecular Insights

Cited by 10 publications

References 261 publications

Cancer causes dysfunctional insulin signaling and glucose transport in a muscle‐type‐specific manner

Cancer causes dysfunctional insulin signaling and glucose transport in a muscle‐type‐specific manner

Cancer causes dysfunctional insulin signaling and glucose transport in a muscle-type specific manner

Weight Change in Post-Menopausal Women with Breast Cancer during Chemotherapy—Perspectives on Nutrition, Activity and Bone Metabolism: An Interim Analysis of a 5-Year Prospective Cohort

Contact Info

Product

Resources

About