The impact of peripheral serotonin on leptin-brain serotonin axis, bone metabolism and strength in growing rats with experimental chronic kidney disease

Pawlak, Dariusz; Domaniewski, Tomasz; Znorko, Beata; Oksztulska-Kolanek, Ewa; Lipowicz, Paweł; Doroszko, Michał; Karbowska, Małgorzata; Pawlak, Krystyna

doi:10.1016/j.bone.2017.08.004

Cited by 23 publications

(14 citation statements)

References 42 publications

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“…Our previous study showed that the elevated levels of peripherally synthesized 5-HT may influence the strength and metabolism of a long bone in nephrectomized rats [8]. We also identified a new molecular pathway, via which elevated circulating 5-HT can affect the expression of 5-HT-dependent genes in bone, shifting in forkhead box protein O1 (FOXO1) target genes from a cAMP-responsive element-binding protein (CREB)-to an activating transcription factor 4 (ATF4)-dependent response, resulting in enhanced osteoblast differentiation in this model [9].…”

Section: Introductionmentioning

confidence: 93%

Modulation of the Paracrine Kynurenic System in Bone as a New Regulator of Osteoblastogenesis and Bone Mineral Status in an Animal Model of Chronic Kidney Disease Treated with LP533401

Mor

Pawlak

Kałaska

et al. 2020

IJMS

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An increase in the peripheral synthesis of serotonin and kynurenine, observed during the chronic kidney disease (CKD) course, is negatively associated with bone health. Serotonin and kynurenine are connected by the common precursor, tryptophan. LP533401 is an inhibitor of peripheral serotonin synthesis. This study aimed to establish if the inhibition of serotonin synthesis by LP533401 may affect the kynurenine pathway activity in bone tissue and its potential consequence with regard to osteogenesis and bone mineral status. Nephrectomized rats were treated with LP533401 at a dose of 30 and 100 mg/kg daily for eight weeks. Tryptophan and kynurenine concentrations were determined, and tryptophan 2,3-dioxygenase (TDO) expression was assessed. We discovered the presence of a TDO-dependent, paracrine kynurenic system in the bone of rats with CKD. Its modulation during LP533401 treatment was associated with impaired bone mineral status. Changes in TDO expression affecting the kynurenine pathway activity were related to the imbalance between peripheral serotonin and 25-hydroxyvitamin D. There were also close associations between the expression of genes participating in osteoblastogenesis and activation of the kynurenine pathway in the bones of LP53301-treated rats. Our results represent the next step in studying the role of tryptophan metabolites in renal osteodystrophy.

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Section: Introductionmentioning

confidence: 93%

Modulation of the Paracrine Kynurenic System in Bone as a New Regulator of Osteoblastogenesis and Bone Mineral Status in an Animal Model of Chronic Kidney Disease Treated with LP533401

Mor

Pawlak

Kałaska

et al. 2020

IJMS

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“…Recent studies 13 , 14 , 32 have begun to reveal a close relationship between the gut microbiome and OP. Li et al 14 reported that the lack of sex steroid did not drive the expansion of T cells and instead increased the production of TNF-α, IL-17, and RANKL in bone marrow and intestine in GF mice.…”

Section: Roles Of the Gut Microbiome In Osteoporosismentioning

confidence: 99%

Gut microbiome and osteoporosis

Mao

Zhou

et al. 2020

Bone & Joint Research

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Osteoporosis (OP) is a chronic metabolic bone disease characterized by the decrease of bone tissue per unit volume under the combined action of genetic and environmental factors, which leads to the decrease of bone strength, makes the bone brittle, and raises the possibility of bone fracture. However, the exact mechanism that determines the progression of OP remains to be underlined. There are hundreds of trillions of symbiotic bacteria living in the human gut, which have a mutually beneficial symbiotic relationship with the human body that helps to maintain human health. With the development of modern high-throughput sequencing (HTS) platforms, there has been growing evidence that the gut microbiome may play an important role in the programming of bone metabolism. In the present review, we discuss the potential mechanisms of the gut microbiome in the development of OP, such as alterations of bone metabolism, bone mineral absorption, and immune regulation. The potential of gut microbiome-targeted strategies in the prevention and treatment of OP was also evaluated. Cite this article: Bone Joint Res 2020;9(8):524–530.

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“…Thyroid, is closely influencing the kidney function (21). Substitutive treatment of subclinical hypothyroidism has a protective effect on the residual renal function of chronic kidney disease, which will impede the progression of the disease (22,23). Our study showed that CKD stage 3 and CKD stage 4 patients after treatment had higher levels of hemoglobin, left and right hand grip strength, BMI compare to the untreated patients.…”

Section: Discussionmentioning

confidence: 55%

Favorable Effect of Levothyroxine on Nutritional Status of Patients with Stage 3-4 Chronic Kidney Disease

Tang

Chen

et al. 2018

Acta Endo (Buc)

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The aim of this study was to analyze the incidence of malnutrition in patients with stage 3-4 chronic kidney disease (CKD) and primary subclinical hypothyroidism and the effect of levothyroxine for improving nutritional status and delaying kidney disease. Patients and Methods. In the study were included 200 patients with stage 3-4 CKD: CKD3 stage group (n=100) and CKD4 stage group (n=100). These patients were further divided into: control group (non-treatment group) group a (n=65) and experiment group (treatment group) group b (n=135) according to their levothyroxine treatment. The CKD3 stage group is divided into c3 (n=35) and e3 (n=65), and CKD4 group is divided into c4 (n=30) and e4 (n=70) groups. Results. Upon treatment of subclinical hypothyroidism with levothyroxine, nutritional indicators of patients are improved, and the weight, left and right-hand grip strength, hemoglobin (HB), serum albumin are higher compared to control. After levothyroxine treatment, eGFR in the treatment group increased with each time point, while in the control group it could be seen a significant decrease. This effect was more robust in the CKD3 group than in the CKD4 group. In conclusion, levothyroxine treatment can delay the progression of kidney diseases with more efficacy in stage 3 patients.

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The impact of peripheral serotonin on leptin-brain serotonin axis, bone metabolism and strength in growing rats with experimental chronic kidney disease

Cited by 23 publications

References 42 publications

Modulation of the Paracrine Kynurenic System in Bone as a New Regulator of Osteoblastogenesis and Bone Mineral Status in an Animal Model of Chronic Kidney Disease Treated with LP533401

Modulation of the Paracrine Kynurenic System in Bone as a New Regulator of Osteoblastogenesis and Bone Mineral Status in an Animal Model of Chronic Kidney Disease Treated with LP533401

Gut microbiome and osteoporosis

Favorable Effect of Levothyroxine on Nutritional Status of Patients with Stage 3-4 Chronic Kidney Disease

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