Background: The exonic variant rs6265 in the brain-derived neurotrophic factor (BDNF) has repeatedly been linked to obesity.
Objective: To discern the factors by which this effect is conveyed we aimed to investigate its correlation with obesity and metabolic parameters as well as with serum levels of BDNF and measures of energy intake in children. Secondly, we aimed to compare levels of circulating BDNF with metabolic parameters.
Methods: We genotyped the variant in 2131 obese and lean children and adolescents (age 6-18 years). In 177 subjects, we determined BDNF serum levels by ELISA and assessed the association with metabolic parameters and data on eating habits from self-reported food diaries.
Results: The minor Met-allele was associated with lower body weight (p=0.002). In the entire study cohort none of the investigated metabolic parameters was associated with the variant. When looking at postpubertal subjects, we observed decreased postprandial glucose levels and a decreased HbA1c in Met-allele-carriers after adjusting for BMI (p=0.046 and p=0.012, respectively). Serum BDNF did not differ between homozygous Val/Val-individuals and carriers of the Met-allele. We neither found a correlation of serum BDNF with different genotypes nor with any of the metabolic parameters.
Conclusion: We confirmed the association of the minor Met-allele with decreased body weight in children and additionally observed alterations in postprandial glucose metabolism in postpubertal subjects. However, variations in serum levels of BDNF were neither related to the genotype nor to the phenotype of food intake or glucose metabolism.:Inhaltsverzeichnis 2
Abkürzungsverzeichnis 3
1 Einführung in die Thematik 4
1.1 Genetische Ursachen von Adipositas 4
1.2 Der neuronale Wachstumsfaktor BDNF 5
1.3 BDNF und Regulation von Nahrungsaufnahme und Glukosemetabolismus 6
1.4 Der exonisch gelegene Val66Met-Polymorphismus in BDNF 7
1.5 Oraler Glukosetoleranztest und HbA1c als Marker des Glukosestoffwechsels 9
1.5.1 Physiologische Grundlagen der Glukosehomöostase 9
1.5.2 OGTT und Insulinsensitivitätsindizes 10
1.5.3 HbA1c – das „Langzeitgedächtnis“ des Blutzuckerspiegels 10
1.6 Basisdiagnostik des Fettstoffwechsels 11
1.7 Einschätzung der Nährstoffaufnahme mittels Ernährungstagebuch 11
2 Überleitung zur Publikation 13
2.1 Ziel der Arbeit, Rationale und Fragestellung 13
2.2 Charakterisierung der Kohorten 14
2.3 Kurzbeschreibung der Methoden 15
2.4 Ergebnisse 15
2.5 Fazit 16
3 Originalpublikation 17
4 Zusammenfassung 30
5 Literaturverzeichnis 35
6 Anlagen 39
6.1 Erklärung über die eigenständige Abfassung der Arbeit 39
6.2 Spezifizierung des eigenen wissenschaftlichen Beitrages 40
6.3 Danksagung 41
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:79770 |
| Date | 29 June 2022 |
| Creators | Kalenda, Agnes |
| Contributors | Universität Leipzig |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | German |
| Detected Language | English |
| Type | info:eu-repo/semantics/acceptedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 10.1111/ijpo.12238 |
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