Keppner 2020 Thesis
|Keppner G (2020) Impact of gut microbiota composition, liver metabolism and respiratory capacity of peripheral blood mononuclear cells on resting metabolic rate. PhD Thesis 100.|
Abstract: Obesity is a worldwide health problem with an increasing incidence over the last decades. Treatments include a reduction of energy intake and an increase in energy expenditure, which require a precise knowledge about the daily energy expenditure and its components. Resting metabolic rate (RMR) is with 60 - 80% the biggest component of daily energy expenditure and therefore of special interest. RMR is characterized by a high inter-individual variation. Variables taken into consideration when predicting RMR are sex, age, race, fat mass and fat free mass (FFM). However, even after adjusting RMR for these influencing variables, a residual variation of approximately 30% remains unexplained. In the present work the impact of liver metabolism, gut microbiota composition and the respiratory capacity of peripheral blood mononuclear cells (PBMCs) on RMR variation is analyzed.
To analyze the residual variation of RMR, a general linear regression model was designed, based on the four enable cohorts with 488 subjects ranging from 3 to 85 years. At first a mixed effect model was generated with the variables sex, age, fat mass, FFM and body temperature, resulting in a correlation coefficient of R2 = 0.80. This equation was crossvalidated in an independent cohort with a high precision of R2 = 0.79. The mixed effect model was applied to analyze the influence of clinical blood parameters and blood pressure on RMR variation. Thereby, free triiodothyronine, leukocytes, creatinine, MCHC, systolic blood pressure and heart rate were identified to be significant predictors of RMR. Based on all these variables, a second and more complex statistical model was generated to elucidate the residual variation regarding the influence of liver metabolism, gut microbiota composition and respiratory capacity of PBMCs.
A pilot study with 30 subjects was conducted to analyze the influence of liver fat, as a parameter of liver activity, on RMR variation. Liver fat content was not associated with RMR and did not explain the residual variation of RMR. Gut microbiota composition was determined by 16S rRNA gene sequencing and analyzed in 442 subjects. The analysis of gut microbiota composition on RMR variation was performed by correlation analysis, linear regression analysis, principle component analysis and artificial neural networks. Gut bacterial composition and diversity did not correlate with RMR variation until the level of Operational Taxonomic Units. However, an indirect correlation of bacteria on the family level and RMR was found. This correlation was based on an association with FFM, which is the main predictor of RMR. Mitochondrial activity of PBMCs was determined in 179 subjects by high resolution respirometry. Though, the respiratory capacity of PBMCs was not associated with RMR and therefore did not contribute to the residual variation of RMR.
In summary, the results of the present thesis provide new insights into the involvement of liver metabolism, gut microbiota composition and respiratory capacity of PBMCs on RMR variation. Additionally, an equation with high precision to predict RMR is presented.
Labels: MiParea: Respiration Pathology: Obesity
Organism: Human Tissue;cell: Blood cells Preparation: Permeabilized cells, Intact cells
Coupling state: LEAK, ROUTINE, OXPHOS, ET Pathway: N, S, NS, ROX HRR: Oxygraph-2k