Metabolic homeostasis via BDNF and its receptors

Podyma, Brandon; Parekh, Kavya; Güler, Ali D.; Deppmann, Christopher D.

doi:10.1016/j.tem.2021.04.005

Cited by 55 publications

(37 citation statements)

References 95 publications

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“…Figure 3 shows mRNA expression levels of selected genes in the hypothalamus of 25-day-old male and female rats. These genes were chosen for their role in energy homeostasis and/or because previous studies have shown both alterations in their expression due to gestational calorie restriction and/or a response to leptin treatment during lactation [ 8 , 22 , 40 ]. Interestingly, both male and female rats treated with myo-inositol during the suckling period showed higher Lepr mRNA levels in comparison with CR-V, CR-L, and CR-LM animals (two-way ANOVA).…”

Section: Resultsmentioning

confidence: 99%

“…Despite changes described in leptin and insulin receptor, expression levels of other genes related to the action of these hormones showed no significant differences between groups in the hypothalamus with the exception of Mc4r and Bdnf . Hypothalamic BDNF is an anorectic factor and a regulator of energy expenditure apart from a main neurotrophin, therefore regulating neuronal development [ 40 , 51 ]. The only significant change observed here was that CR males treated with the vehicle displayed a significant increase of Bdnf mRNA levels compared to control animals, which might reflect a compensatory response.…”

Section: Discussionmentioning

confidence: 99%

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Myo-Inositol Supplementation in Suckling Rats Protects against Adverse Programming Outcomes on Hypothalamic Structure Caused by Mild Gestational Calorie Restriction, Partially Comparable to Leptin Effects

et al. 2021

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We studied whether myo-inositol supplementation throughout lactation, alone and combined with leptin, may reverse detrimental effects on hypothalamic structure and function caused by gestational calorie gestation (CR) in rats. Candidate early transcript-based biomarkers of metabolic health in peripheral blood mononuclear cells (PBMC) were also studied. Offspring of dams exposed to 25% gestational CR and supplemented during lactation with physiological doses of leptin (CR-L), myo-inositol (CR-M), the combination (CR-LM), or the vehicle (CR-V) as well as control rats (CON-V) were followed and sacrificed at postnatal day 25. Myo-inositol and the combination increased the number of neurons in arcuate nucleus (ARC) (only in females) and paraventricular nucleus, and myo-inositol (alone) restored the number of αMSH+ neurons in ARC. Hypothalamic mRNA levels of Lepr in CR-M and Insr in CR-M and CR-LM males were higher than in CR-V and CON-V, respectively. In PBMC, increased expression levels of Lrp11 and Gls in CR-V were partially normalized in all supplemented groups (but only in males for Gls). Therefore, myo-inositol supplementation throughout lactation, alone and combined with leptin, reverts programmed alterations by fetal undernutrition on hypothalamic structure and gene expression of potential early biomarkers of metabolic health in PBMC, which might be attributed, in part, to increased leptin sensitivity.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Myo-Inositol Supplementation in Suckling Rats Protects against Adverse Programming Outcomes on Hypothalamic Structure Caused by Mild Gestational Calorie Restriction, Partially Comparable to Leptin Effects

et al. 2021

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“…Neurotrophins (e.g., brain-derived neurotrophic factor (BDNF]) play an important role in regulating energy and glucose homeostasis (for example, in cholesterol metabolism) not only in neuronal differentiation [ 55 ] but also in peripheral tissues [ 56 ]; therefore, they are also associated with inflammatory diseases, as well as MetS [ 57 , 58 , 59 , 60 ]. BDNF activity is mediated through the TrkB receptor [ 61 ] and the neurotrophin receptor p75 (p75NTR), also known as the low-affinity nerve growth factor receptor, which belongs to the TNF-receptor superfamily [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Leptin Receptor (rs1137101) and Brain-Derived Neurotrophic Factor (rs925946) Gene Variants Are Associated with Obesity in the Early- but Not in the Late-Onset Population of Hungarian Psoriatic Patients

Szentkereszty-Kovács

Fiatal

Janka

et al. 2021

Life

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Background: Psoriatic patients have considerably higher odds of being obese compared with the general population; however, the exact pathophysiological link between psoriasis and obesity needs to be elucidated. Methods: To investigate the association of psoriasis with established obesity-related gene variants, we conducted a population-based case-control study including 3541 subjects (574 psoriasis cases and 2967 controls from the general Hungarian population). Genotyping of 20 SNPs at ADIPOQ, BDNF, FTO, GNPDA2, LEPR, MC4R, NEGR1, NPY, PPARG, TMEM18, and UCP2 were determined, and differences in genotype and allele distributions were investigated. Multiple logistic regression analyses were implemented. Results: Analysis revealed an association between the G allele of the rs1137101 polymorphism (LEPR gene) and obesity risk (OR: 3.30 (1.45; 7.50), p = 0.004) in the early-onset group of psoriatic patients. Furthermore, the T allele of rs925946 polymorphism (BDNF gene) was also associated with increased risk of obesity in early-onset psoriasis (OR: 2.26 (1.24; 4.14) p = 0.008). Conclusions: Our results suggest that in psoriatic patients, there are prominent differences in the causes of obesity that should be accounted for, including not only environmental factors but also patient characteristics, such as the time of disease onset as well as genetic factors.

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“…Therefore, to maintain energy balance, organisms have to evaluate changes in energy needs considering several factors such as physical activity and thermoregulation. Hormones such as insulin, leptin, PYY and ghrelin, allow this tightly regulated information exchange [9][10][11]. Alongside hormones, emerging players in the energy balance regulation are neurotrophins, most notably, BDNF and its receptor, both abundantly expressed in several regions of hypothalamus and hindbrain [3,12].…”

Section: The Role Of Bdnf In the Central Control Of Energy Balancementioning

confidence: 99%

“…The involvement of BDNF in the central regulation of feeding was noticed earlier during investigations aiming at improving the knowledge about how BDNF regulates learning, memory, synaptic transmission and plasticity [11]. The intracerebroventricular (ICV) injection of BDNF in rats to evaluate the neurotrophic effect in the treatment of Alzheimer's also induced appetite suppression and weight loss [13,14].…”

Section: The Role Of Bdnf In the Central Control Of Energy Balancementioning

confidence: 99%

The Pleiotropic Potential of BDNF beyond Neurons: Implication for a Healthy Mind in a Healthy Body

Rosa

Zimbone

Saab

et al. 2021

Life

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Brain-derived neurotrophic factor (BDNF) represents one of the most widely studied neurotrophins because of the many mechanisms in which it is involved. Among these, a growing body of evidence indicates BDNF as a pleiotropic signaling molecule and unveils non-negligible implications in the regulation of energy balance. BDNF and its receptor are extensively expressed in the hypothalamus, regions where peripheral signals, associated with feeding control and metabolism activation, and are integrated to elaborate anorexigenic and orexigenic effects. Thus, BDNF coordinates adaptive responses to fluctuations in energy intake and expenditure, connecting the central nervous system with peripheral tissues, including muscle, liver, and the adipose tissue in a complex operational network. This review discusses the latest literature dealing with the involvement of BDNF in the maintenance of energy balance. We have focused on the physiological and molecular mechanisms by which BDNF: (I) controls the mitochondrial function and dynamics; (II) influences thermogenesis and tissue differentiation; (III) mediates the effects of exercise on cognitive functions; and (IV) modulates insulin sensitivity and glucose transport at the cellular level. Deepening the understanding of the mechanisms exploited to maintain energy homeostasis will lay the groundwork for the development of novel therapeutical approaches to help people to maintain a healthy mind in a healthy body.

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Metabolic homeostasis via BDNF and its receptors

Cited by 55 publications

References 95 publications

Myo-Inositol Supplementation in Suckling Rats Protects against Adverse Programming Outcomes on Hypothalamic Structure Caused by Mild Gestational Calorie Restriction, Partially Comparable to Leptin Effects

Myo-Inositol Supplementation in Suckling Rats Protects against Adverse Programming Outcomes on Hypothalamic Structure Caused by Mild Gestational Calorie Restriction, Partially Comparable to Leptin Effects

Leptin Receptor (rs1137101) and Brain-Derived Neurotrophic Factor (rs925946) Gene Variants Are Associated with Obesity in the Early- but Not in the Late-Onset Population of Hungarian Psoriatic Patients

The Pleiotropic Potential of BDNF beyond Neurons: Implication for a Healthy Mind in a Healthy Body

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