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Brain-derived neurotrophic factor (BDNF) gene expression was measured in human skeletal muscle following 3 intensities of exercise and a 48-h fast. No change in BDNF mRNA was observed following exercise, while fasting upregulated BDNF by ∼3.5-fold. These changes were dissociated from changes in peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) following exercise (+2- to 15-fold) and fasting (∼-25%). These results challenge our understanding of the response of BDNF to energetic stress and highlight the importance of future work in this area.
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... Serum BDNF seems to increase in response to an acute bout of exercise, in an intensity-dependent fashion (Tonoli et al. 2015a, b), and this may explain the absence of impact on BDNF when performing light intensity PA. Moreover, no change in BDNF mRNA was observed in human skeletal muscle following exercise, while fasting upregulated BDNF by ∼ 3.5-fold (Walsh et al. 2015). This finding indicates that our understanding on the response of BDNF to energetic stress is far from being certain. ...
... However, this may be explained by the fact that most of the previous investigations examined the benefits of acute forms of exercise training on BDNF levels (Dinoff et al. 2017;Roh et al. 2017;Rasmussen et al. 2009;Tonoli et al. 2015a, b) and our cross-sectional data may not reflect an acute impact. In fact, there is evidence in humans showing that resting levels of BDNF are not affected by chronic exercise or PA levels (Walsh et al. 2015;Szuhany et al. 2015), and that the acute effect of exercise (i.e. BDNF to increase up to two-to three-fold) disappears 30-60 min following cessation from exercise (Walsh and Tschakovsky 2018;Rasmussen et al. 2009). ...
Article
During the recovery period, athletes present high sedentary behavior (SB). In non-athletes, there is a direct relationship between SB and obesity. However, little is known about this relationship in athletes. We hypothesized that different types of SB entail different associations with body composition outcomes. We examined the associations between different types of SB and body composition outcomes in 135 athletes (70 males) aged 21.3±3.9 years old. Dual-energy X-ray absorptiometry was performed to assess fat mass (FM), fat-free mass (FFM), and trunk fat mass (TFM). A validated SB questionnaire (PACE) was used to estimate total SB and specific sedentary pursuits on an average day. Multiple linear regression analyses were performed, adjusting for age, sex, weekly training time, years of sport practice, and sport type. A positive association was found for total SB and total screen time with %TFM (β=0.220, p=0.038 and β=0.319, p=0.040, respectively), while an inverse association was found for %FFM (β=-0.214, p=0.042 and β=-0.310, p=0.026). A higher total screen time was related with a higher %FM (β=0.283, p=0.035). With a much stronger effect size, cell phone screen time was positively related with %FM (β=1.447, p=0.001). There is still debate whether high levels of physical activity can fully counteract the harms of SB. These findings suggest that SB, particularly cell phone screen time, can compromise athletes' body composition, regardless of weekly training time. Sport federations and coaches may improve athletes' body composition by targeting specific sedentary pursuits, i.e. total screen time and cell phone screen time, during athletes' recovery time.
... Serum BDNF seems to increase in response to an acute bout of exercise, in an intensity-dependent fashion (Tonoli et al. 2015a, b), and this may explain the absence of impact on BDNF when performing light intensity PA. Moreover, no change in BDNF mRNA was observed in human skeletal muscle following exercise, while fasting upregulated BDNF by ∼ 3.5-fold (Walsh et al. 2015). This finding indicates that our understanding on the response of BDNF to energetic stress is far from being certain. ...
... However, this may be explained by the fact that most of the previous investigations examined the benefits of acute forms of exercise training on BDNF levels (Dinoff et al. 2017;Roh et al. 2017;Rasmussen et al. 2009;Tonoli et al. 2015a, b) and our cross-sectional data may not reflect an acute impact. In fact, there is evidence in humans showing that resting levels of BDNF are not affected by chronic exercise or PA levels (Walsh et al. 2015;Szuhany et al. 2015), and that the acute effect of exercise (i.e. BDNF to increase up to two-to three-fold) disappears 30-60 min following cessation from exercise (Walsh and Tschakovsky 2018;Rasmussen et al. 2009). ...
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Purpose Exercise is beneficial to type-2 diabetes-mellitus (T2DM), and there is evidence showing that one of those benefits include a higher expression of brain-derived neurotrophic factor (BDNF), which has been implicated in improving fat oxidation and cognitive development. The deleterious effect of prolonged sedentary time (ST) on BDNF levels has never been examined in patients with T2DM. Our goal was to analyse the associations for sedentary patterns [i.e. breaks in ST per sedentary hour (BST-ST) and bouts of sedentary time (BSB) of different length] with BDNF in patients with T2DM, independent of moderate-to-vigorous physical activity (MVPA) and cardiorespiratory fitness (CRF). Methods Sample included 80 patients (38 women) with T2DM (58.3 ± 7.8 years). ST and MVPA were assessed by accelerometry (ActiGraph, GT3X + model), BDNF by blood collection and plasma quantification using commercial enzyme-linked immunosorbent assay kits, and CRF was determined using a Bruce protocol to exhaustion, on a motorized treadmill. Results Positive associations for BST-ST (β = 0.155; p = 0.007) with BDNF, and negative associations for BSB longer than 15 min with BDNF were found (β = − 0.118; p = 0.049). Neither MVPA nor cardiorespiratory fitness eliminated the associations for BST-ST with BDNF, but MVPA eradicated the associations between BSB > 15 min and BDNF. Conclusions Our findings suggest that interrupting ST and especially avoiding longer sedentary periods (> 15 min) may be beneficial for BDNF plasma abundance that may influence metabolic and cognitive functioning of patients with T2DM, especially for the ones presenting lower MVPA levels. Trial registration May 5, 2017, ClinicalTrials.govID:NCT03144505
... Taking into account the different protocols of physical exercise, mainly resistance and aerobic (high-intensity or moderate-intensity performed at continuous or intermittent form) training, several studies have shown their effects on speed and cognition accuracy [101], information processing in CNS [102], neurocognitive performance [103], BDNF regulation [104,105] and myokines production, which is related to improvement in cognitive function as FNDC5, irisin and cathepsin B increase [100]. ...
... Tonoli et al. [137] Patients with type 1 diabetes (n=10) maximize physical exercise training performance might benefit not only cardiometabolic but also cognitive health via modulated brain metabolism and morphology. Thus, considering regular exercise training, individuals with higher physical fitness status have lower brain tissue losses, especially in frontal, parietal, and temporal cortex [115], higher brain perfusion and responsiveness of blood vessel [116], and greater neurotrophins production [104,117]. These adaptations are some of the hypotheses considered to explain the positive impact of physical fitness status in brain health improvement, providing a plausible biological mechanism to explain the benefits of exercise training. ...
Article
Background The number of individuals with obesity is growing worldwide and this is a worrying trend as obesity has shown to cause pathophysiological changes which result in the emergence of comorbidities such as cardiovascular disease, diabetes mellitus and cancer. In addition, cognitive performance may be compromised by immunometabolic deregulation of obesity. Although in more critical cases the use of medications is recommended, a physically active lifestyle is one of the main foundations for health maintenance, making physical training an important tool to reduce the harmful effects of excessive fat accumulation. Aim The purpose of this review of the literature is to present the impact of immunometabolic alterations on cognitive function in individuals with obesity, and the role of exercise training as a non-pharmacological approach to improve the inflammatory profile, energy metabolism and neuroplasticity in obesity. Method An overview of the etiology and pathophysiology of obesity to establish a possible link with cognitive performance in obese individuals, with executive function being one of the most affected cognitive components. In addition, the brain-derived neurotrophic factor (BDNF) profile and its impact on cognition in obese individuals is discussed. Lastly, studies showing regular resistance and/or aerobic training which may be able to improve pathophysiological condition and cognitive performance through the improvement of the inflammatory profile, decreased insulin resistance and higher BDNF production are discussed. Conclusion Exercise training is essential to reestablishment and maintenance of health by increasing energy expenditure, insulin resistance reduction, anti-inflammatory proteins and neurotrophin production corroborating to upregulation of body function.
... These findings suggest that the reduction in circulating BDNF levels during 4-week-IF could be due to increased cellular uptake and expression at the tissue level in response to nutrient deprivation. In fact, a study showed an approximately 3.5 fold increase in the BDNF mRNA expression in the human muscle tissue after 48-h fasting [21]. ...
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Background Brain-derived neurotrophic factor (BDNF) is a key neurotrophin that regulates food intake and energy hemostasis. BDNF also promotes neurogenesis, neuroplasticity, and neuroprotection. There are conflicting reports regarding how intermittent fasting affects circulating BDNF levels. We tested the hypothesis that 4-week intermittent fasting from dawn to sunset (4-week-IF) would decrease circulating BDNF levels in subjects with metabolic syndrome and healthy subjects. Methods We conducted pilot studies in subjects with metabolic syndrome and healthy subjects who fasted from dawn to sunset for more than 14 h for four consecutive weeks. We measured serum BDNF levels and metabolic parameters before 4-week-IF, at the end of 4th week during 4-week-IF, and one week after 4-week-IF. Results We enrolled 28 subjects, 14 with metabolic syndrome (women/men:6/8) with a mean age of 59 years and 14 healthy subjects (women/men:1/13) with a mean age of 32 years. Overall, BDNF levels decreased at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF (mean paired difference = −98.5 ng/ml, P = 0.0006). When subjects with metabolic syndrome were compared with healthy subjects, subjects with metabolic syndrome had a lower mean paired reduction in BDNF levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF (BDNF mean paired difference = −27.6 ng/ml vs. −169.5 ng/ml, P = 0.003). Multivariate linear regression analysis showed a positive correlation between the change in tumor necrosis factor-alpha and change in BDNF levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF in subjects with metabolic syndrome (P = 0.040) and healthy subjects (P = 0.007). The change in weight and body mass index independently predicted the change in BDNF levels 1 week after 4-week-IF compared with the levels before 4-week-IF in subjects with metabolic syndrome. Conclusion Four-week-IF resulted in a reduction in the BDNF levels at the end of 4th week during 4-week-IF. Higher BDNF levels and a lower reduction in BDNF levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF in subjects with metabolic syndrome than healthy subjects suggest a potential BDNF resistance similar to insulin and leptin resistance in metabolic syndrome. A positive correlation between the change in BDNF and change in tumor necrosis factor-alpha levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF suggests that BDNF is a biomarker of inflammation and endothelial dysfunction in addition to its neurotrophic and anorexigenic features.
... Cross-sectional evidence in humans shows a negative gradient relationship between body mass index (BMI), glycemic control, and plasma BDNF such that lean, normoglycemic individuals had the highest plasma BDNF and people with obesity and type 2 diabetes (T2D) had the lowest (Krabbe et al., 2007). BDNF expression is sensitive to energy status, and energetic stressors like exercise and fasting upregulate BDNF expression (Walsh et al., 2015;Dinoff et al., 2017). Conversely, acute hyperglycemia reduces cerebral output of BDNF in young adults, which may be a mechanism to explain lower plasma BDNF in adults with T2D (Krabbe et al., 2007). ...
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Brain-derived neurotrophic factor (BDNF) is important for brain and metabolic function. Ingestion of a ketone monoester (KME) drink containing beta-hydroxybutyrate (β-OHB) attenuates hyperglycemia in humans and increases neuronal BDNF in rodents. Whether KME affects BDNF in humans is currently unknown. This study examined the effect of KME ingestion before an oral glucose tolerance test (OGTT) on plasma BDNF in normal-weight adults (NW) and adults with obesity (OB). Methods: Exploratory, secondary analyses of two studies were performed. Study 1 included NW (n = 18; age = 25.3 ± 4.3 years; BMI = 22.2 ± 2.3 kg/m2) and Study 2 included OB (n = 12; age = 48.8 ± 9.5 years; BMI = 33.7 ± 5.0 kg/m2). Participants ingested 0.45 ml/kg−1 body weight KME or Placebo 30-min prior to completing a 75 g OGTT. β-OHB and BDNF were measured via blood samples at fasting baseline (pre-OGTT) and 120 min post-OGTT. Results: Study 1: KME significantly increased β-OHB by 800 ± 454% (p < 0.001). BDNF significantly decreased post-OGTT compared to pre-OGTT in Placebo (718.6 ± 830.8 pg/ml vs. 389.3 ± 595.8 pg/ml; p = 0.018), whereas BDNF was unchanged in KME (560.2 ± 689.6 pg/ml vs. 469.2 ± 791.8 pg/ml; p = 0.28). Study 2: KME significantly increased β-OHB by 1,586 ± 602% (p < 0.001). BDNF was significantly higher post-OGTT in the KME condition in OB (time × condition interaction; p = 0.037). There was a moderate relationship between β-OHB and ∆ %BDNF (r = 0.616; p < 0.001). Fasting plasma BDNF was significantly lower in OB compared to NW (132.8 ± 142.8 pg/ml vs. 639.4 ± 756.8 pg/ml; g = 0.845; p = 0.002). Conclusions: Plasma BDNF appears differentially impacted by KME ingestion with OGTT in OB compared to NW. Raising β-OHB via KME may be a strategy for increasing/protecting BDNF during hyperglycemia.
... We show here that such decrease is also found in rat TIB, especially during P3. It has also been reported previously that mRNA levels of brain-derived neurotrophic factor (BDNF) are higher in the vastus lateralis muscle from 48 h-fasted humans [97], however BDNF gene expression remained unchanged in rat TIB in our study. Discrepancies depending on the species and/or muscle considered is not surprising. ...
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Food deprivation resulting in muscle atrophy may be detrimental to health. To better understand how muscle mass is regulated during such a nutritional challenge, the current study deciphered muscle responses during phase 2 (P2, protein sparing) and phase 3 (P3, protein mobilization) of prolonged fasting in rats. This was done using transcriptomics analysis and a series of biochemistry measurements. The main findings highlight changes for plasma catabolic and anabolic stimuli, as well as for muscle transcriptome, energy metabolism, and oxidative stress. Changes were generally consistent with the intense use of lipids as fuels during P2. They also reflected increased muscle protein degradation and repressed synthesis, in a more marked manner during P3 than P2 compared to the fed state. Nevertheless, several unexpected changes appeared to be in favor of muscle protein synthesis during fasting, notably at the level of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, transcription and translation processes, and the response to oxidative stress. Such mechanisms might promote protein sparing during P2 and prepare the restoration of the protein compartment during P3 in anticipation of food intake for optimizing the effects of an upcoming refeeding, thereby promoting body maintenance and survival. Future studies should examine relevance of such targets for improving nitrogen balance during catabolic diseases.
... Cross-sectional evidence in humans shows a negative gradient relationship between body mass index (BMI), glycemic control, and plasma BDNF such that lean, normoglycemic individuals had the highest plasma BDNF and people with obesity and type 2 diabetes (T2D) had the lowest (Krabbe et al., 2007). BDNF expression is sensitive to energy status, and energetic stressors like exercise and fasting upregulate BDNF expression (Walsh et al., 2015;Dinoff et al., 2017). Conversely, acute hyperglycemia reduces cerebral output of BDNF in young adults, which may be a mechanism to explain lower plasma BDNF in adults with T2D (Krabbe et al., 2007). ...
... Fasting can be distinguished from caloric J o u r n a l P r e -p r o o f restriction in that its health benefits in humans and animals appear to arise from the duration between meals, rather than the total calories consumed (Paoli et al., 2019). Intermittant fasting can positively impact ageing brain health (Mattson, 2015) and has been observed to upregulate BDNF expression by up to three times (Walsh, Edgett, et al., 2015). While it is unclear whether intermittent fasting or caloric restriction provides superior BDNF release, but fasting for a clear block of time rather than consistent caloric restriction appears to be more achieveable for human subjects (Anton & Leeuwenburgh, 2013). ...
Article
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Physical activity has received substantial research attention due to its beneficial impact on cognition in ageing, particularly via the action of brain-derived neurotrophic factor (BDNF). It is well established that physical activity can elevate circulating levels of BDNF, and that BDNF has neurotrophic, neuroprotective and cognitively beneficial properties. Yet, practical implementation of this knowledge is limited by a lack of clarity on context and dose-effect. Against a shifting backdrop of gradually diminishing physical and cognitive capacity in normal ageing, the type, intensity, and duration of physical activity required to elicit elevations in BDNF, and more importantly, the magnitude of BDNF elevation required for detectable neuroprotection remains poorly characterised. The purpose of this review is to provide an overview of the association between physical activity, BDNF, and cognition, with a focus on clarifying the magnitude of these effects in the context of normative ageing. We discuss the implications of the available evidence for the design of physical activity interventions intended to promote healthy cognitive ageing.
... Still, even if peripheral blood lactate concentrations are associated with serum BDNF concentrations (Ferris et al., 2007;Schiffer et al., 2011), further studies will be required to investigate the dose-response relationship between exercise prescription and (serum) BDNF levels (Knaepen et al., 2010;Coelho et al., 2013;Huang et al., 2014). Since BDNF release is also influenced by several other non-modifiable (e.g., sex Trajkovska et al., 2007;Komulainen et al., 2010;Bus et al., 2011) or non-exercise-related modifiable factors (e.g., sleep or nutrition; Giese et al., 2013Giese et al., , 2014Walsh et al., 2015;Schmitt et al., 2016) that are known to influence neuroplasticity in general (e.g., sleep, Meerlo et al., 2009;Raven et al., 2018;or nutrition, Greenwood and Parasuraman, 2010;Phillips, 2017;Poulose et al., 2017), these factors should be carefully monitored in further studies. ...
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In general, it is well-recognized that both acute physical exercises and regular physical training influence brain plasticity and cognitive functions positively. However, growing evidence shows that the same physical exercises induce very heterogeneous outcomes across individuals. In an attempt to better understand this interindividual heterogeneity in response to acute and regular physical exercising, most research, so far, has focused on non-modifiable factors such as sex and different genotypes, while relatively little attention has been paid to exercise prescription as a modifiable factor. With an adapted exercise prescription dosage can be made comparable across individuals, a procedure which is necessary to better understand the dose-response relationship in exercise-cognition research. This improved understanding of dose-response relationships could help to design more efficient physical training approaches against, for instance, cognitive decline.
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Muscle activation as well as changes in peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1a) following high-intensity interval exercise (HIIE) were examined in young healthy men (n = 8; age, 21.962.2 yrs; VO 2 peak, 53.166.4 ml/min/kg; peak work rate, 317623.5 watts). On each of 3 visits HIIE was performed on a cycle ergometer at a target intensity of 73, 100, or 133% of peak work rate. Muscle biopsies were taken at rest and three hours after each exercise condition. Total work was not different between conditions (,730 kJ) while average power output (73%, 237621; 100%, 323626; 133%, 384635 watts) and EMG derived muscle activation (73%, 12626605; 100%, 20896737; 133%, 302961206 total integrated EMG per interval) increased in an intensity dependent fashion. PGC-1a mRNA was elevated after all three conditions (p,0.05), with a greater increase observed following the 100% condition (,9 fold, p,0.05) compared to both the 73 and 133% conditions (,4 fold). When expressed relative to muscle activation, the increase in PGC-1a mRNA for the 133% condition was less than that for the 73 and 100% conditions (p,0.05). SIRT1 mRNA was also elevated after all three conditions (,1.4 fold, p,0.05), with no difference between conditions. These findings suggest that intensity-dependent increases in PGC-1a mRNA following submaximal exercise are largely due to increases in muscle recruitment. As well, the blunted response of PGC-1a mRNA expression following supramaximal exercise may indicate that signalling mediated activation of PGC-1a may also be blunted. We also indentify that increases in PDK4, SIRT1, and RIP140 mRNA following acute exercise are dissociated from exercise intensity and muscle activation, while increases in EGR1 are augmented with supramaximal HIIE (p,0.05).
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Obesity in humans is often associated with metabolic inflexibility but the underlying molecular mechanisms remain incompletely understood. The aim of the present study was to investigate how adaptation to prolonged fasting affects energy/nutrient-sensing pathways and metabolic gene expression in skeletal muscle from lean and obese individuals. Twelve lean and 14 non-diabetic obese subjects were fasted for 48 hours. Whole-body glucose/lipid oxidation rates were determined by indirect calorimetry and blood and skeletal muscle biopsies were collected and analyzed. In response to fasting, body weight loss was similar in both groups but the decrease in plasma insulin and leptin, and the concomitant increase in growth hormone were significantly attenuated in obese subjects. The fasting-induced shift from glucose toward lipid oxidation was also severely blunted. At molecular level, the expression of insulin receptor β (IRβ) was lower in skeletal muscle from obese subjects at baseline, whereas the fasting-induced reductions in insulin signaling were similar in both groups. The protein expression of mitochondrial respiratory-chain components, although not modified by fasting, was significantly reduced in obese subjects. Some minor differences in metabolic gene expression were observed at baseline and in response to fasting. Surprisingly, fasting reduced AMP-activated protein kinase (AMPK) activity in lean but not in obese subjects, whereas the expression of AMPK subunits was not affected. We conclude that whole-body metabolic inflexibility in response to prolonged fasting in obese humans is associated with lower skeletal muscle IRβ and mitochondrial respiratory-chain content as well as a blunted decline of AMPK activity.
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Gene regulatory factors encoded by the nuclear genome are essential for mitochondrial biogenesis and function. Some of these factors act exclusively within the mitochondria to regulate the control of mitochondrial transcription, translation, and other functions. Others govern the expression of nuclear genes required for mitochondrial metabolism and organelle biogenesis. The peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) family of transcriptional coactivators play a major role in transducing and integrating physiological signals governing metabolism, differentiation, and cell growth to the transcriptional machinery controlling mitochondrial functional capacity. Thus, the PGC-1 coactivators serve as a central component of the transcriptional regulatory circuitry that coordinately controls the energy-generating functions of mitochondria in accordance with the metabolic demands imposed by changing physiological conditions, senescence, and disease.
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Emerging findings suggest that brain-derived neurotrophic factor (BDNF) serves widespread roles in regulating energy homeostasis by controlling patterns of feeding and physical activity, and by modulating glucose metabolism in peripheral tissues. BDNF mediates the beneficial effects of energetic challenges such as vigorous exercise and fasting on cognition, mood, cardiovascular function, and on peripheral metabolism. By stimulating glucose transport and mitochondrial biogenesis BDNF bolsters cellular bioenergetics and protects neurons against injury and disease. By acting in the brain and periphery, BDNF increases insulin sensitivity and parasympathetic tone. Genetic factors, a 'couch potato' lifestyle, and chronic stress impair BDNF signaling, and this may contribute to the pathogenesis of metabolic syndrome. Novel BDNF-focused interventions are being developed for obesity, diabetes, and neurological disorders.
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Exercise can improve cognitive function and has been linked to the increased expression of brain-derived neurotrophic factor (BDNF). However, the underlying molecular mechanisms driving the elevation of this neurotrophin remain unknown. Here we show that FNDC5, a previously identified muscle protein that is induced in exercise and is cleaved and secreted as irisin, is also elevated by endurance exercise in the hippocampus of mice. Neuronal Fndc5 gene expression is regulated by PGC-1α, and Pgc1a(-/-) mice show reduced Fndc5 expression in the brain. Forced expression of FNDC5 in primary cortical neurons increases Bdnf expression, whereas RNAi-mediated knockdown of FNDC5 reduces Bdnf. Importantly, peripheral delivery of FNDC5 to the liver via adenoviral vectors, resulting in elevated blood irisin, induces expression of Bdnf and other neuroprotective genes in the hippocampus. Taken together, our findings link endurance exercise and the important metabolic mediators, PGC-1α and FNDC5, with BDNF expression in the brain.
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The neurotrophin system has a role in skeletal muscle biology. Conditional depletion of BDNF in mouse muscle precursor cells alters myogenesis and regeneration in vivo. However, the expression, localisation and function of BDNF in human skeletal muscle tissue is not known so the relevance of the rodent findings for human muscle are unknown. Here we address this by combining ex vivo histological investigations on human biopsies with in vitro analyses of human primary myocytes. We found that BDNF was expressed by precursor and differentiated cells both in vitro and in vivo. Differential analysis of BDNF receptors showed expression of p75NTR and not of TrkB in myocytes, suggesting that the BDNF-p75NTR axis is predominant in human skeletal muscle cells. Several in vitro functional experiments demonstrated that BDNF gene silencing or protein blockade in myoblast cultures hampered myogenesis. Finally, histological investigations of inflammatory myopathy biopsies revealed that infiltrating immune cells localised preferentially near p75NTR positive regenerating fibers and that they produced BDNF. In conclusion, BDNF is an autocrine factor for skeletal muscle cells and may regulate human myogenesis. Furthermore, the preferential localisation of BDNF producing immune cells near p75NTR positive regenerating myofibers suggests that immune cell derived BDNF may sustain tissue repair in inflamed muscle.