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1.
Molecular Basis of the Beneficial Actions of Resveratrol.
Repossi, G, Das, UN, Eynard, AR
Archives of medical research. 2020;(2):105-114
Abstract
Resveratrol modulates the transcription factor NF-κB, cytochrome P450 isoenzyme CYP1A1, expression and activity of cyclooxygenase (COX) enzymes, Fas/Fas ligand mediated apoptosis, p53, mTOR and cyclins and various phospho-diesterases resulting in an increase in cytosolic cAMP levels. Cyclic AMP, in turn, activates Epac1/CaMKKβ/AMPK/SIRT1/PGC-1α pathway that facilitates increased oxidation of fatty acids, mitochondrial respiration and their biogenesis and gluconeogenesis. Resveratrol triggers apoptosis of activated T cells and suppresses tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17) and other pro-inflammatory molecules and inhibits expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) that may explain its anti-inflammatory actions. Polyunsaturated fatty acids (PUFAs) and their anti-inflammatory metabolites lipoxin A4, resolvins, protectins and maresins have a significant role in obesity, type 2 diabetes mellitus (T2DM), metabolic syndrome and cancer. We observed that PUFAs (especially arachidonic acid, AA) and BDNF (brain-derived neurotrophic factor) protect against the cytotoxic actions of alloxan, streptozotocin, benzo(a)pyrene (BP) and doxorubicin. Thus, there is an overlap in the beneficial actions of resveratrol, PUFAs and BDNF suggesting that these molecules may interact and augment synthesis and action of each other. This is supported by the observation that resveratrol and PUFAs modulate gut microbiota and influence stem cell proliferation and differentiation. Since resveratrol is not easily absorbed from the gut it is likely that it may act on endocannabinoid and light, odor, and taste receptors located in the gut, which, in turn, convey their messages to the various organs via vagus nerve.
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2.
Developmental origins of adult health and disease: The metabolic role of BDNF from early life to adulthood.
Briana, DD, Malamitsi-Puchner, A
Metabolism: clinical and experimental. 2018;:45-51
Abstract
Accumulating evidence suggests that the origins of adult disease may occur during fetal life. Thus, the concept of "developmental programming" has been introduced and supported by epidemiological and experimental data. This concept supports the idea that the nutritional and hormonal status during pregnancy could interfere in metabolism control. The mechanisms responsible for this "developmental programming" remain poorly documented. Current research indicates that neurotrophins and particularly brain-derived neurotrophic factor (BDNF) may play a crucial role in this process. Although mainly expressed in the nervous system, BDNF and its receptor, tropomyosin-related kinase B (TrkB), are immunolocalized in several regions of the human placenta and have important functions during pregnancy. BDNF serves widespread roles in regulating energy homeostasis in both fetuses and adults, by controlling patterns of fetal growth, adult feeding and physical activity, and by regulating glucose metabolism in peripheral tissues. Impaired BDNF signaling may be implicated in the etiopathogenesis of the metabolic syndrome. Novel BDNF-focused interventions are being developed for obesity, diabetes and neurological disorders. The aim of this article is to provide a brief comprehensive literary review regarding the potential implications of BDNF in "developmental programming", through regulation of metabolism and energy balance from early life to adulthood.
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Relationship between body weight and the increment in serum brain-derived neurotrophic factor after oral glucose challenge in men with obesity and metabolic syndrome: A prospective study.
Lee, IT, Wang, JS, Fu, CP, Lin, SY, Sheu, WH
Medicine. 2016;(43):e5260
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Abstract
Brain-derived neurotrophic factor (BDNF) plays a role in energy homeostasis. However, the postprandial BDNF change has not been well investigated. We hypothesized that the BDNF increment after oral glucose challenge is associated with body weight.To address this possibility, man adults with obesity in conjunction with metabolic syndrome were compared with normal weight controls at baseline in the initial cross-sectional protocol. The obese subjects then underwent a 12-week program for body-weight reduction in the prospective protocol. The area under the curve (AUC) of serum BDNF was recorded during a 75 g oral glucose tolerant test and the BDNF AUC index was defined as [(AUC of BDNF) - (fasting BDNF2 hours)]/(fasting BDNF2 hours).A total of 25 controls and 36 obese subjects completed the study assessments. In the cross-sectional protocol, the BDNF AUC index was significantly higher in the obese subjects than in the controls (9.0 ± 16.5% vs. - 8.0 ± 22.5%, P = 0.001). After weight reduction (from 97.0 ± 12.5 kg to 88.6 ± 12.9 kg, P < 0.001), the percentage change of body weight was significantly associated with the BDNF AUC index after the study (95% CI between 0.21 and 1.82, P = 0.015). Using 6% weight reduction as a cut-off value, a larger weight reduction was able to reliably predict a negative BDNF AUC index.In conclusion, a high BDNF AUC index was observed for obese men in this study, whereas the index value significantly decreased after body-weight reduction. These findings suggest that postprandial BDNF increment may be associated with obesity.
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Correlation of plasma brain-derived neurotrophic factor and metabolic profiles in drug-naïve patients with bipolar II disorder after a twelve-week pharmacological intervention.
Lee, SY, Chen, SL, Chang, YH, Chen, PS, Huang, SY, Tzeng, NS, Wang, CL, Wang, LJ, Lee, IH, Wang, TY, et al
Acta psychiatrica Scandinavica. 2015;(2):120-8
Abstract
OBJECTIVE Brain-derived neurotrophic factor (BDNF) is thought to be involved in the pathophysiology of bipolar disorder (BD) and metabolic syndrome. We investigated the correlation between plasma BDNF with mood symptoms and metabolic indices in patients with BD-II over a 12-week pharmacological intervention. METHOD Drug-naïve patients with BD-II (n=117) were recruited. Metabolic profiles [cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI)] and plasma BDNF wtrun "tblautotrun "tblsctrun "tbl_contere measured at baseline and 2, 8, and 12 weeks after beginning medication. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used. RESULTS Seventy-six (65.0%) patients completed the intervention. Plasma BDNF levels were significantly associated with BMI (P=9.6E-5), low-density lipoprotein (P=0.034) and total (P=0.001) cholesterol, but not with the Hamilton Depression Rating Scale-17 and Young Mania Rating Scale scores over the 12-week treatment. CONCLUSION We found initial evidence of a positive correlation between plasma BDNF levels and BMI, low-density lipoprotein and total cholesterol in drug-naïve patients with BD-II. The specific function of BDNF in regulating and maintaining peripheral metabolic health requires additional investigation.
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The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with increased body mass index and insulin resistance measures in bipolar disorder and schizophrenia.
Bonaccorso, S, Sodhi, M, Li, J, Bobo, WV, Chen, Y, Tumuklu, M, Theleritis, C, Jayathilake, K, Meltzer, HY
Bipolar disorders. 2015;(5):528-35
Abstract
OBJECTIVES We tested the hypothesis that a common functional variant in brain-derived neurotrophic factor (BDNF), Val66Met, which has been shown to be associated with increased body mass index (BMI) in schizophrenia (SCZ) and schizoaffective disorder (SAD), is also associated with antipsychotic-induced weight gain in bipolar disorder (BPD). Association of Val66Met with other metabolic measures, including high- and low-density cholesterol, triglycerides, total cholesterol, fasting blood glucose, and hemoglobin A1c, was also tested. METHODS This was a 12-month, prospective, randomized trial of two atypical antipsychotic drugs (APDs) with moderate (risperidone) or high (olanzapine) risk to cause weight gain. Subjects were diagnosed as having BPD (n = 90) and SCZ or SAD (n = 76). RESULTS BMI was significantly greater in all diagnoses for Met66 allele carriers at six months (p = 0.01). Met66 carriers with BPD showed a greater increase in the triglycerides/high-density (HDL) cholesterol ratio (p = 0.01), a key marker for metabolic syndrome related to insulin resistance, and log-triglycerides (p = 0.04), after three or six months of treatment. Met66 carriers had the greatest increase in log-triglycerides (p = 0.03) and triglycerides/HDL cholesterol ratio after three months of treatment with risperidone (p = 0.003), and the highest BMI at six months (p = 0.01). CONCLUSIONS The positive association of BNDF Val66Met with high BMI values replicates previous findings in patients with SCZ and indicates the BDNF Val66Met genotype as a potential risk factor for obesity and insulin resistance measures in patients with BPD receiving antipsychotics as well.
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Brain-derived neurotrophic factor correlated with muscle strength in subjects undergoing stationary bicycle exercise training.
Tsai, SW, Chan, YC, Liang, F, Hsu, CY, Lee, IT
Journal of diabetes and its complications. 2015;(3):367-71
Abstract
AIMS: Several central nervous disorders are associated with metabolic syndrome (MetS) and type 2 diabetes. Reduction in brain-derived neurotrophic factor (BDNF) is involved in the mechanism of central nervous dysfunction. BDNF is up-regulated after exercise, but it is not known whether increased BDNF is related to increases in muscle strength. METHODS In the present study, subjects with MetS or type 2 diabetes were enrolled in an exercise program. All participants underwent an indoor bicycle exercise program for twelve weeks. Serum BDNF was determined after overnight fasting. Muscle strength was assessed by extension of the dominant lower extremity. RESULTS A total of 33 subjects were enrolled in this study. The body mass index did not change significantly (from 30.4±6.0 to 30.2±5.8kg/m(2), P=0.436), but serum BDNF increased significantly (from 17.1±9.1 to 24.2±10.7ng/mL, P<0.001) after the study. The exercise-associated BDNF was significantly correlated with the increased strength in lower-extremity extension test (r=0.54, P=0.001). Using multivariate regression analysis, muscle-strength increment, but not body-weight change, was an independent factor for serum BDNF (95% CI=0.009-0.044, P=0.005). CONCLUSIONS After a twelve-week program of stationary bicycle exercise, serum BDNF concentration increased, and this change was positively correlated with muscle strength of lower-extremity extension, but not body weight. ( TRIAL REGISTRATION NCT02268292, ClinicalTrials.gov).
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Influence of aerobic training and detraining on serum BDNF, insulin resistance, and metabolic risk factors in middle-aged men diagnosed with metabolic syndrome.
Damirchi, A, Tehrani, BS, Alamdari, KA, Babaei, P
Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine. 2014;(6):513-8
Abstract
OBJECTIVE To study the influence of aerobic exercise training on brain-derived neurotrophic factor (BDNF), insulin resistance, and lipid profile in middle-aged men diagnosed with metabolic syndrome (MetS). DESIGN This is an experimental repeated measure study. SETTING Subjects participated in aerobic training programs (18 sessions of 25-40 minutes per session) in Guilan University gymnasium and court. PARTICIPANTS A total of 21 middle-aged men (50-65 years old) diagnosed with MetS participated. INTERVENTIONS We randomly divided 21 middle-aged men with MetS into exercise and control groups. The exercise group followed an aerobic training program (18 sessions, 3/wk) at 50% to 60% of V[Combining Dot Above]O2 peak (25-40 minutes per session) and 6 weeks of detraining. Blood samples were collected at baseline, end of the training, and detraining. MAIN OUTCOME MEASURES High BDNF level in patients with MetS and its reduction after chronic aerobic exercise. RESULTS Aerobic training significantly decreased all the metabolic risk factors, including overall MetS z score, insulin resistance, and lipid profile (P < 0.05). After the detraining period, plasma triglyceride, high-density lipoprotein, and also overall MetS z score remained unchanged (P < 0.05); however, serum BDNF, which was decreased by aerobic training (P = 0.013), restored to the baseline at the end of the detraining (P = 0.018). CONCLUSIONS Improved metabolic risk factors along with decreased serum BDNF in response to aerobic training and the opposite direction during the detraining emphasize the importance of physical activity in the treatment of MetS and prevention of related diseases.
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BDNF, metabolic risk factors, and resistance training in middle-aged individuals.
Levinger, I, Goodman, C, Matthews, V, Hare, DL, Jerums, G, Garnham, A, Selig, S
Medicine and science in sports and exercise. 2008;(3):535-41
Abstract
INTRODUCTION AND PURPOSE Brain-derived neurotrophic factor (BDNF) and physical inactivity contribute to the development of the metabolic syndrome (MetS). There appears to be an association between BDNF and risk factors for MetS, and the effects of resistance training (RT) on BDNF and metabolic risk in middle-aged individuals with high and low numbers of metabolic risk factors (HiMF and LoMF, respectively) are unclear and are the focus of this research. METHODS Forty-nine men (N = 25) and women (N = 24) aged 50.9 +/- 6.2 yr were randomized to four groups, HiMF training (HiMFT), HiMF control (HiMFC), LoMF training (LoMFT), and LoMF control (LoMFC). Before and after 10 wk of RT, participants underwent tests for muscle strength and anthropometry, and a fasting blood sample was taken. Data were analyzed using Spearman correlations and repeated-measures ANOVA. RESULTS BDNF was positively correlated with plasma triglycerides, glucose, HbA1C, and insulin resistance. BDNF was elevated in HiMF compared with LoMF (904.9 +/- 270.6 vs 709.6 +/- 239.8 respectively, P = 0.01). Training increased muscle strength and lean body mass but had no effect on BDNF levels or any examined risk factors. CONCLUSION BDNF levels correlated with risk factors for MetS and were elevated in individuals with HiMF. RT had no effect on BDNF levels or other risk factors for MetS. As RT has an effect on muscle strength and lean body mass, it should be added to other nonpharmacological interventions for middle-aged individuals with HiMF such as aerobic and/or diet.