Induction of Growth Differentiation Factor 15 in Skeletal Muscle of Old Taurine Transporter Knockout Mouse

Ito, Takashi; Nakanishi, Yusuke; Yamaji, Noriko; Murakami, Shigeru; Schaffer, Stephen W.

doi:10.1248/bpb.b17-00969

Cited by 16 publications

(8 citation statements)

References 32 publications

(40 reference statements)

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“…As it is known that strenuous exercise induces GDF15 expression (20)(21)(22), it has been hypothesized that also skeletal muscle can be a source of this cytokine. Accordingly, GDF15 is expressed in muscles from mouse models of aging and inactivity (12,14). However, this idea has been recently challenged, as the concentrations of GDF15 during a physical exercise resulted similar in arterial and venous blood across the exercised leg (22).…”

Section: Discussionmentioning

confidence: 99%

“…As far as muscle atrophy and sarcopenia, there is debate on whether GDF15 is to be considered protective or detrimental. Recent data from animal models showed that GDF15 is able to induce muscle fiber apoptosis (12,13), but also the ablation of GDF15 resulted in an amplified skeletal muscle post exercise stress response, with a bigger increase of markers of muscle stress (Atf3, Atf6, and Xbp1s) (14). In humans, circulating GDF15 levels are significantly higher in subjects with sarcopenia or muscle atrophy (15)(16)(17) with respect to healthy subjects of comparable age.…”

Section: Introductionmentioning

confidence: 99%

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GDF15 Plasma Level Is Inversely Associated With Level of Physical Activity and Correlates With Markers of Inflammation and Muscle Weakness

et al. 2020

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Growth differentiation factor 15 (GDF15) is a stress molecule produced in response to mitochondrial, metabolic and inflammatory stress with a number of beneficial effects on metabolism. However, at the level of skeletal muscle it is still unclear whether GDF15 is beneficial or detrimental. The aim of the study was to analyse the levels of circulating GDF15 in people of different age, characterized by different level of physical activity and to seek for correlation with hematological parameters related to inflammation. The plasma concentration of GDF15 was determined in a total of 228 subjects in the age range from 18 to 83 years. These subjects were recruited and divided into three different groups based on the level of physical activity: inactive patients with lower limb mobility impairment, active subjects represented by amateur endurance cyclists, and healthy controls taken from the general population. Cyclists were sampled before and after a strenuous physical bout (long distance cycling race). The plasma levels of GDF15 increase with age and are inversely associated with active lifestyle. In particular, at any age, circulating GDF15 is significantly higher in inactive patients and significantly lower in active people, such as cyclists before the race, with respect to control subjects. However, the strenuous physical exercise causes in cyclists a dramatic increase of GDF15 plasma levels, that after the race are similar to that of patients. Moreover, GDF15 plasma levels significantly correlate with quadriceps torque in patients and with the number of total leukocytes, neutrophils and lymphocytes in both cyclists (before and after race) and patients. Taken together, our data indicate that GDF15 is associated with decreased muscle performance and increased inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

GDF15 Plasma Level Is Inversely Associated With Level of Physical Activity and Correlates With Markers of Inflammation and Muscle Weakness

et al. 2020

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“…9 GDF15 is also produced by skeletal muscle cells in response to aging-related stress, mitochondrial dysfunction and mitochondrial proteotoxic stress. [10][11][12][13] GDF15 is a useful diagnostic biomarker for mitochondrial diseases, which are caused by mitochondrial or nuclear genomic mutations. 10,11 Mitochondrial dysfunction, along with increased reactive oxygen species generation may result in increased blood GDF15 levels in patients with mitochondrial diseases.…”

Section: Introductionmentioning

confidence: 99%

“…GDF15 is highly expressed in cardiomyocytes, adipocytes, macrophages, endothelial cells and vascular smooth muscle cells in pathological conditions such as inflammation, insulin resistance and oxidative stress 9 . GDF15 is also produced by skeletal muscle cells in response to aging‐related stress, mitochondrial dysfunction and mitochondrial proteotoxic stress 10–13 . GDF15 is a useful diagnostic biomarker for mitochondrial diseases, which are caused by mitochondrial or nuclear genomic mutations 10,11 .…”

Section: Introductionmentioning

confidence: 99%

Serum growth differentiation factor 15 level is associated with muscle strength and lower extremity function in older patients with cardiometabolic disease

Oba¹,

Ishikawa

Tamura³

et al. 2020

Geriatrics Gerontology Int

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Aims: Sarcopenia is a serious problem because of its poor prognosis. Growth differentiation factor 15 (GDF15) is associated with mitochondrial dysfunction, inflammation, insulin resistance and oxidative stress, which may play crucial roles for the development of sarcopenia. We aimed to examine whether serum GDF15 level is associated with muscle mass, strength and lower extremity function in older patients with cardiometabolic disease. Methods: Serum GDF15 levels were measured in 257 patients with cardiometabolic diseases (including 133 patients with diabetes) who had visited the frailty clinic, using a latex turbidimetric immunoassay. Appendicular skeletal muscle index, handgrip strength, timed-upand-go test and gait speed were evaluated. Power, speed, balance and total scores based on the sit-to-stand test were calculated to assess lower extremity function. Results: The highest tertile of serum GDF15 was independently associated with low handgrip strength, low gait speed, long timed-up-and-go time and scores of lower extremity function but not an appendicular skeletal muscle index in multiple logistic regression analyses after adjustment for covariates. Patients in the highest tertile of GDF15 were at the risk of having three to nine times lower grip strength, three times lower gait speed, five to six times lower mobility and five to 11 times reduction in lower extremity function as compared with those in the lowest GDF15 tertile dependent on the models. Conclusions: Elevated serum GDF15 level was independently associated with low muscle strength and lower extremity function in older patients with cardiometabolic disease. Serum GDF15 could be one of the biomarkers for muscle weakness and low physical performance.

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“…In a recent study, levels of GDF-15 detected in blood plasma increased with time over a 7 day period of ICU stay, alongside a simultaneous and significant decline in muscle strength score and CSA of the rectus femoris for those with ICUAW [ 205 ]; this trend was not seen in the non-ICUAW group [ 205 ]. Since GDF-15 appears to play a role in numerous other pathological conditions, such as cancer and sarcopenia [ 206 ], further investigation of the GDF-15 influence in different cell types and disease conditions is warranted. Importantly, these findings offer proof-of-principle that blood-borne mediators may act as biomarkers and drug targets for new therapeutic interventions.…”

Section: Knowledge Gaps and Avenues To New Insightsmentioning

confidence: 99%

Intensive Care Unit-Acquired Weakness: Not Just Another Muscle Atrophying Condition

Lad

Saumur

Herridge

et al. 2020

IJMS

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Intensive care unit-acquired weakness (ICUAW) occurs in critically ill patients stemming from the critical illness itself, and results in sustained disability long after the ICU stay. Weakness can be attributed to muscle wasting, impaired contractility, neuropathy, and major pathways associated with muscle protein degradation such as the ubiquitin proteasome system and dysregulated autophagy. Furthermore, it is characterized by the preferential loss of myosin, a distinct feature of the condition. While many risk factors for ICUAW have been identified, effective interventions to offset these changes remain elusive. In addition, our understanding of the mechanisms underlying the long-term, sustained weakness observed in a subset of patients after discharge is minimal. Herein, we discuss the various proposed pathways involved in the pathophysiology of ICUAW, with a focus on the mechanisms underpinning skeletal muscle wasting and impaired contractility, and the animal models used to study them. Furthermore, we will explore the contributions of inflammation, steroid use, and paralysis to the development of ICUAW and how it pertains to those with the corona virus disease of 2019 (COVID-19). We then elaborate on interventions tested as a means to offset these decrements in muscle function that occur as a result of critical illness, and we propose new strategies to explore the molecular mechanisms of ICUAW, including serum-related biomarkers and 3D human skeletal muscle culture models.

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Induction of Growth Differentiation Factor 15 in Skeletal Muscle of Old Taurine Transporter Knockout Mouse

Cited by 16 publications

References 32 publications

GDF15 Plasma Level Is Inversely Associated With Level of Physical Activity and Correlates With Markers of Inflammation and Muscle Weakness

GDF15 Plasma Level Is Inversely Associated With Level of Physical Activity and Correlates With Markers of Inflammation and Muscle Weakness

Serum growth differentiation factor 15 level is associated with muscle strength and lower extremity function in older patients with cardiometabolic disease

Intensive Care Unit-Acquired Weakness: Not Just Another Muscle Atrophying Condition

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