Incorporating Refractory Period in Mechanical Stimulation Mitigates Obesity‐Induced Adipose Tissue Dysfunction in Adult Mice

Patel, Vihitaben S.; Chan, M. Ete; Pagnotti, Gabriel M.; Frechette, Danielle M.; Rubin, Janet; Rubin, Clinton T.

doi:10.1002/oby.21958

Cited by 19 publications

(23 citation statements)

References 43 publications

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“…An additional effect of exercise on the bone is increased mechanical stress for skeletal system induced by whole body vibration (WBV), which has been shown to improve bone density by reducing bone marrow adiposity in mice and humans and restoring lymphopoiesis (increased number of B cells). WBV also showed an effect on immune cells in circulation and induced lower infiltration in AT (162,163). A key strategy to prevent obesity and its complications, including bone health, is a combination of exercise and a well-balanced diet.…”

Section: Life-style Interventions: Dietary and Physical Activity Intementioning

confidence: 98%

Obesity-Induced Changes in Bone Marrow Homeostasis

Beňová

Tencerová

2020

Front. Endocrinol.

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Obesity is characterized by low-grade inflammation, which is accompanied by increased accumulation of immune cells in peripheral tissues including adipose tissue (AT), skeletal muscle, liver and pancreas, thereby impairing their primary metabolic functions in the regulation of glucose homeostasis. Obesity has also shown to have a detrimental effect on bone homeostasis by altering bone marrow and hematopoietic stem cell differentiation and thus impairing bone integrity and immune cell properties. The origin of immune cells arises in the bone marrow, which has been shown to be affected with the obesogenic condition via increased cellularity and shifting differentiation and function of hematopoietic and bone marrow mesenchymal stem cells in favor of myeloid progenitors and increased bone marrow adiposity. These obesity-induced changes in the bone marrow microenvironment lead to dramatic bone marrow remodeling and compromising immune cell functions, which in turn affect systemic inflammatory conditions and regulation of whole-body metabolism. However, there is limited information on the inflammatory secretory factors creating the bone marrow microenvironment and how these factors changed during metabolic complications. This review summarizes recent findings on inflammatory and cellular changes in the bone marrow in relation to obesity and further discuss whether dietary intervention or physical activity may have beneficial effects on the bone marrow microenvironment and whole-body metabolism.

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Section: Life-style Interventions: Dietary and Physical Activity Intementioning

confidence: 98%

Obesity-Induced Changes in Bone Marrow Homeostasis

Beňová

Tencerová

2020

Front. Endocrinol.

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“…By contrast, high-intensity resistance plus impact training improved both BMD and physical function in postmenopausal women with osteoporosis 8 . The inherent complexity of exercise-generated mechanical challenges for skeletal tissues 50 indicates that some components of the load-bearing regimen might be more influential than others 51,52 .…”

Section: Mechanical Influences On Bonementioning

confidence: 99%

Combating osteoporosis and obesity with exercise: leveraging cell mechanosensitivity

et al. 2019

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Osteoporosis, a condition of skeletal decline that undermines quality of life, is treated with pharmacological interventions that are associated with poor adherence and adverse effects. Complicating efforts to improve clinical outcomes, the incidence of obesity is increasing, predisposing the population to a range of musculoskeletal complications and metabolic disorders. Pharmacological management of obesity has yet to deliver notable reductions in weight and debilitating complications are rarely avoided. By contrast, exercise shows promise as a non-invasive and non-pharmacological method of regulating both osteoporosis and obesity. The principal components of exercise — mechanical signals — promote bone and muscle anabolism while limiting formation and expansion of fat mass. Mechanical regulation of bone and marrow fat might be achieved by regulating functions of differentiated cells in the skeletal tissue while biasing lineage selection of their common progenitors — mesenchymal stem cells. An inverse relationship between adipocyte versus osteoblast fate selection from stem cells is implicated in clinical conditions such as childhood obesity and increased marrow adiposity in type 2 diabetes mellitus, as well as contributing to skeletal frailty. Understanding how exercise-induced mechanical signals can be used to improve bone quality while decreasing fat mass and metabolic dysfunction should lead to new strategies to treat chronic diseases such as osteoporosis and obesity.

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“…28 These findings mimic responses in mice where incorporation of a refractory period between bouts of mechanical stimulation diminished obesity-induced adipose accumulation. 16 In this study, incorporation of a refractory period between bouts of mechanical vibration resulted in greater effects compared to once-daily treatment for some endpoints but not all. Twice-daily LIV resulted in significantly decreased invasion compared to non-vibrated cells, while there was no change compared to controls for once-daily LIV.…”

Section: Discussionmentioning

confidence: 72%

“…14 The effects of LIV are additive, with a second bout of LIV enhancing FAK phosphorylation and F-actin contractility. 15 The additive benefits observed with a second bout of mechanical stimuli have also been shown in animal 16 and human studies, 17 suggesting that proper dosing primes the cells to generate a more robust response with subsequent mechanical stimuli.…”

Section: Introductionmentioning

confidence: 88%

Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity

Wright

Pagnotti

et al. 2020

Bone Res

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Exercise benefits the musculoskeletal system and reduces the effects of cancer. The effects of exercise are multifactorial, where metabolic changes and tissue adaptation influence outcomes. Mechanical signals, a principal component of exercise, are anabolic to the musculoskeletal system and restrict cancer progression. We examined the mechanisms through which cancer cells sense and respond to low-magnitude mechanical signals introduced in the form of vibration. Low-magnitude, high-frequency vibration was applied to human breast cancer cells in the form of low-intensity vibration (LIV). LIV decreased matrix invasion and impaired secretion of osteolytic factors PTHLH, IL-11, and RANKL. Furthermore, paracrine signals from mechanically stimulated cancer cells, reduced osteoclast differentiation and resorptive capacity. Disconnecting the nucleus by knockdown of SUN1 and SUN2 impaired LIV-mediated suppression of invasion and osteolytic factor secretion. LIV increased cell stiffness; an effect dependent on the LINC complex. These data show that mechanical vibration reduces the metastatic potential of human breast cancer cells, where the nucleus serves as a mechanosensory apparatus to alter cell structure and intercellular signaling.

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Incorporating Refractory Period in Mechanical Stimulation Mitigates Obesity‐Induced Adipose Tissue Dysfunction in Adult Mice

Cited by 19 publications

References 43 publications

Obesity-Induced Changes in Bone Marrow Homeostasis

Obesity-Induced Changes in Bone Marrow Homeostasis

Combating osteoporosis and obesity with exercise: leveraging cell mechanosensitivity

Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity

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