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The role of secreted bacterial metabolites in regulating adipose biology: the effect of the Lab4 consortium of probiotics on adipogenesis

Roberts, Duncan 2017. The role of secreted bacterial metabolites in regulating adipose biology: the effect of the Lab4 consortium of probiotics on adipogenesis. MPhil Thesis, Cardiff University.
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The gut microbiota has come to be viewed as an extrasomatic organ influencing human health. Obesity is a major global public health challenge urgently requiring development of new treatments. Reports of weight gain after faecal microbial transplant have spurred interest in the potential role of the microbiota in obesity in man. Lab4 and Lab4b are commercially available probiotic products that have recently been shown to be associated with decreased weight gain in high-fat diet mice, and have recently been used to investigate in vitro adipogenesis. Brown adipose tissue is highly metabolically active, and is inversely associated with BMI. Bacterial metabolites such as lactate have been shown to induce “browning” of adipose tissue. The effects of Lab4 and Lab4b cell free supernatant were assessed on in vitro adipogenesis using the 3T3-L1 cell line and human primary preadipocytes. Transcriptional markers of adipose phenotype were assessed in 3T3-L1 cells maintained in culture media containing cell free supernatant of the constituent strains of the Lab4/Lab4b consortia. Lab4 and Lab4b were found to significantly reduce lipid accumulation in late adipogenesis in 3T3-L1 cells, though cell morphology suggested paradoxical acceleration of adipogenesis. Reduced lipid accumulation was likely related to a significant reduction in cell viability. Transcriptional markers of adipogenesis were not significantly altered by treatment, nor were markers of adipose phenotype, but transcripts of UCP1 (the functional protein of brown adipose tissue) were significantly higher in non-differentiating cells maintained in cell free supernatant of two L. acidophilus strains (p=0.008). Assessment of effects in human primary preadipocytes were inconclusive due to cytotoxicity, though treatment with Lab4b appears to dramatically alter cellular morphology and increase what appears morphologically to be lipid accumulation in surviving cells. Further study and more robust data is needed to determine the effects of Lab4/Lab4b and their constituent strains on in vitro adipogenesis.

Item Type: Thesis (MPhil)
Status: Unpublished
Schools: Medicine
Date of First Compliant Deposit: 28 March 2018
Last Modified: 11 Dec 2020 03:24

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