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Metabolomics for studying diabetes and obesity

Rogova, Oksana LU (2024)
Abstract
Introduction: Obesity continues to be a growing problem and places a significant burden on the healthcare system by increasing the risk of developing various diseases including type 2 diabetes (T2D). T2D, in turn, increases the risk of developing other diseases, such as cardiovascular diseases (CVDs), neuropathy, and nephropathy. Furthermore, obesity and T2D are closely linked to liver diseases, particularly metabolic dysfunction-associated steatotic liver disease (MASLD). Various strategies exist to overcome obesity, including lifestyle modification, food supplements, pharmaceuticals, and more invasive surgical methods. In this thesis, the impact of various obesity prevention strategies on metabolism is assessed using metabolomics and... (More)
Introduction: Obesity continues to be a growing problem and places a significant burden on the healthcare system by increasing the risk of developing various diseases including type 2 diabetes (T2D). T2D, in turn, increases the risk of developing other diseases, such as cardiovascular diseases (CVDs), neuropathy, and nephropathy. Furthermore, obesity and T2D are closely linked to liver diseases, particularly metabolic dysfunction-associated steatotic liver disease (MASLD). Various strategies exist to overcome obesity, including lifestyle modification, food supplements, pharmaceuticals, and more invasive surgical methods. In this thesis, the impact of various obesity prevention strategies on metabolism is assessed using metabolomics and lipidomics.

Methods: I applied liquid and gas chromatography coupled with mass spectrometry to obtain metabolite and lipid profiles, followed by statistical analysis of the resulting data. In Paper I, I evaluated the effect of Roux-en-Y gastric bypass surgery (RYGB) on human metabolism within a few months and a few years post-surgery. In Paper II, I studied the effect of caffeine supplementation on metabolism in the healthy liver, both in vivo and in vitro. In Paper III, I examined the effect of meals enriched in carbohydrates, fats, protein, or fibre on individuals with type 1 and type 2 diabetes, as well as normoglycaemic individuals.

Results and Discussion: In Paper I, I found that the majority of changes in the metabolome and lipidome occurred within two months after RYGB, after which the metabolic profiles began to reverse, moving towards their initial state. In Paper II, I did not find any metabolite or lipid to be significantly altered due to caffeine supplementation in models of the healthy liver, suggesting that the beneficial effect of caffeine may only be found in the diseased liver. In Paper III, I found metabolism to differ between individuals based on their glycaemic status and in response to variations in meal composition. Minor differences were observed in the diabetes status-dependent response to meal variation.

Conclusion: RYGB significantly affected the human metabolome, however, these changes were transient, and within few months after surgery, metabolic profiles began to shift back towards their initial state. The beneficial effect of caffeine supplementation on liver was not observed in models of the healthy liver. The lack of diabetes status-dependent responses to meal variation suggests that diets that are healthy in people without diabetes are also healthy in people with diabetes. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Associate professor Malmendal, Anders, Department of Science and Environmental Chemistry, Roskilde University.
organization
publishing date
type
Thesis
publication status
published
subject
keywords
metabolomics, lipidomics, diabetes, obesity, chromatography, mass spectrometry
pages
184 pages
publisher
Media-Tryck, Lund University, Sweden
defense location
Kemicentrum, Sal KC:A
defense date
2024-10-30 13:00:00
ISBN
978-91-8096-065-6
978-91-8096-064-9
language
English
LU publication?
yes
id
c302394a-0d0b-4089-8c5f-836945e7d5ec
date added to LUP
2024-10-03 11:43:19
date last changed
2024-10-04 13:33:05
@phdthesis{c302394a-0d0b-4089-8c5f-836945e7d5ec,
  abstract     = {{Introduction: Obesity continues to be a growing problem and places a significant burden on the healthcare system by increasing the risk of developing various diseases including type 2 diabetes (T2D). T2D, in turn, increases the risk of developing other diseases, such as cardiovascular diseases (CVDs), neuropathy, and nephropathy. Furthermore, obesity and T2D are closely linked to liver diseases, particularly metabolic dysfunction-associated steatotic liver disease (MASLD). Various strategies exist to overcome obesity, including lifestyle modification, food supplements, pharmaceuticals, and more invasive surgical methods. In this thesis, the impact of various obesity prevention strategies on metabolism is assessed using metabolomics and lipidomics.<br/><br/>Methods: I applied liquid and gas chromatography coupled with mass spectrometry to obtain metabolite and lipid profiles, followed by statistical analysis of the resulting data. In Paper I, I evaluated the effect of Roux-en-Y gastric bypass surgery (RYGB) on human metabolism within a few months and a few years post-surgery. In Paper II, I studied the effect of caffeine supplementation on metabolism in the healthy liver, both in vivo and in vitro. In Paper III, I examined the effect of meals enriched in carbohydrates, fats, protein, or fibre on individuals with type 1 and type 2 diabetes, as well as normoglycaemic individuals.<br/><br/>Results and Discussion: In Paper I, I found that the majority of changes in the metabolome and lipidome occurred within two months after RYGB, after which the metabolic profiles began to reverse, moving towards their initial state. In Paper II, I did not find any metabolite or lipid to be significantly altered due to caffeine supplementation in models of the healthy liver, suggesting that the beneficial effect of caffeine may only be found in the diseased liver. In Paper III, I found metabolism to differ between individuals based on their glycaemic status and in response to variations in meal composition. Minor differences were observed in the diabetes status-dependent response to meal variation.  <br/><br/>Conclusion: RYGB significantly affected the human metabolome, however, these changes were transient, and within few months after surgery, metabolic profiles began to shift back towards their initial state. The beneficial effect of caffeine supplementation on liver was not observed in models of the healthy liver. The lack of diabetes status-dependent responses to meal variation suggests that diets that are healthy in people without diabetes are also healthy in people with diabetes.}},
  author       = {{Rogova, Oksana}},
  isbn         = {{978-91-8096-065-6}},
  keywords     = {{metabolomics; lipidomics; diabetes; obesity; chromatography; mass spectrometry}},
  language     = {{eng}},
  month        = {{10}},
  publisher    = {{Media-Tryck, Lund University, Sweden}},
  school       = {{Lund University}},
  title        = {{Metabolomics for studying diabetes and obesity}},
  url          = {{https://lup.lub.lu.se/search/files/196436364/PhD_Thesis_Oksana_Rogova.pdf}},
  year         = {{2024}},
}