Metabolomics of Weight Loss and Weight Maintenance in Obese Humans
Year: 2016
Type: dissertation
Abstract: The prevalence of obesity and obesity-related complications are increasing worldwide. Weight loss has shown to improve insulin sensitivity and decrease the risk of developing type 2 diabetes (T2D). Even so, little is known about how metabolites, other than glucose, are affected after weight loss and weight maintenance treatment. Impaired glucose tolerance (IGT) is a common trait of obesity and is studied during an oral glucose tolerance test (OGTT). In this thesis, we identified 16 distinct metabolite OGTT profiles (change from fasting, 30 and 120 min.) that deviated from the glucose tolerant lean group. These deviations were grouped as; a delayed reduction in the levels of five fatty acids, increased levels at 30 min. of five amino acids (incl. isoleucine and leucine), and a blunted increase at 30 min. of six metabolites. When we followed up these obese individuals after weight loss and weight maintenance, roughly half of these metabolites improved towards the expected healthy profile. Specifically, enhanced suppression of aromatic amino acids (tyrosine and phenylalanine) was associated with decreased insulinogenic index after weight loss. On the contrary, the glucose-elicted suppression of four amino acids and three fatty acids improved after weight maintenance, parallelling an improved glucose tolerance. This suggests that diet-induced weight loss followed by weight maintenance results in changes in metabolite OGTT profiles associated with either hepatic insulin sensitivity or peripheral glucose tolerance. Obesity is associated with altered levels of fasting circulating amino acids. We found that eight out of the 18 detected amino acids were associated with obesity, independently of age, sex, T2D and blood pressure. Six of these amino acids were improved after weight maintenance. From this, we created scores based on amino acids and risk factors at baseline that are either informative of the level of association to obesity or the potential benefit, or lack of benefit, by reducing the included amino acids to those that are expected to normalize with a weight loss and weight maintenance program. Finally, we validated previous findings and further explored the data in a larger cohort at baseline and one year after participating in a non-surgical weight loss program. Changed levels in 30 metabolites were uniqe in those with a ≥10% weight loss compared to those with <10% weight loss. In addition, we found weight loss to be associated with 13 baseline metabolite levels, and interestingly, many of these are common food additives. We also saw that the obesity predictive scores were modifiable with weight loss. The thesis adds to the understanding of metabolite alterations in obesity-driven IGT and the benefits of weight loss followed by weight maintenance. Our findings suggest several metabolites that may be valuable to consider when evaluating who will benefit from weight loss treatments.
Author: Nina Geidenstam
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2395975926