Effects of exercise on NAFLD using non-targeted metabolomics in adipose tissue, plasma, urine, and stool
Abstract The mechanisms by which exercise benefits patients with non-alcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, remain poorly understood. A non-targeted liquid chromatography-mass spectrometry (LC–MS)-based metabolomics analysis was used to identify metabolic cha...
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Nature Portfolio
2022-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-10481-9 |
| _version_ | 1818147414216802304 |
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| author | Ambrin Farizah Babu Susanne Csader Ville Männistö Milla-Maria Tauriainen Heikki Pentikäinen Kai Savonen Anton Klåvus Ville Koistinen Kati Hanhineva Ursula Schwab |
| author_facet | Ambrin Farizah Babu Susanne Csader Ville Männistö Milla-Maria Tauriainen Heikki Pentikäinen Kai Savonen Anton Klåvus Ville Koistinen Kati Hanhineva Ursula Schwab |
| author_sort | Ambrin Farizah Babu |
| collection | DOAJ |
| description | Abstract The mechanisms by which exercise benefits patients with non-alcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, remain poorly understood. A non-targeted liquid chromatography-mass spectrometry (LC–MS)-based metabolomics analysis was used to identify metabolic changes associated with NAFLD in humans upon exercise intervention (without diet change) across four different sample types—adipose tissue (AT), plasma, urine, and stool. Altogether, 46 subjects with NAFLD participated in this randomized controlled intervention study. The intervention group (n = 21) performed high-intensity interval training (HIIT) for 12 weeks while the control group (n = 25) kept their sedentary lifestyle. The participants' clinical parameters and metabolic profiles were compared between baseline and endpoint. HIIT significantly decreased fasting plasma glucose concentration (p = 0.027) and waist circumference (p = 0.028); and increased maximum oxygen consumption rate and maximum achieved workload (p < 0.001). HIIT resulted in sample-type-specific metabolite changes, including accumulation of amino acids and their derivatives in AT and plasma, while decreasing in urine and stool. Moreover, many of the metabolite level changes especially in the AT were correlated with the clinical parameters monitored during the intervention. In addition, certain lipids increased in plasma and decreased in the stool. Glyco-conjugated bile acids decreased in AT and urine. The 12-week HIIT exercise intervention has beneficial ameliorating effects in NAFLD subjects on a whole-body level, even without dietary changes and weight loss. The metabolomics analysis applied to the four different sample matrices provided an overall view on several metabolic pathways that had tissue-type specific changes after HIIT intervention in subjects with NAFLD. The results highlight especially the role of AT in responding to the HIIT challenge, and suggest that altered amino acid metabolism in AT might play a critical role in e.g. improving fasting plasma glucose concentration. Trial registration ClinicalTrials.gov (NCT03995056). |
| first_indexed | 2024-12-11T12:34:52Z |
| format | Article |
| id | doaj.art-56bcdb8dcffa4ceaae4877fbdad7d640 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-11T12:34:52Z |
| publishDate | 2022-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-56bcdb8dcffa4ceaae4877fbdad7d6402022-12-22T01:07:10ZengNature PortfolioScientific Reports2045-23222022-04-0112111610.1038/s41598-022-10481-9Effects of exercise on NAFLD using non-targeted metabolomics in adipose tissue, plasma, urine, and stoolAmbrin Farizah Babu0Susanne Csader1Ville Männistö2Milla-Maria Tauriainen3Heikki Pentikäinen4Kai Savonen5Anton Klåvus6Ville Koistinen7Kati Hanhineva8Ursula Schwab9Department of Public Health and Clinical Nutrition, University of Eastern FinlandDepartment of Public Health and Clinical Nutrition, University of Eastern FinlandDepartment of Medicine, University of Eastern Finland and Kuopio University HospitalDepartment of Public Health and Clinical Nutrition, University of Eastern FinlandKuopio Research Institute of Exercise MedicineKuopio Research Institute of Exercise MedicineAfekta Technologies Ltd.Department of Public Health and Clinical Nutrition, University of Eastern FinlandDepartment of Public Health and Clinical Nutrition, University of Eastern FinlandDepartment of Public Health and Clinical Nutrition, University of Eastern FinlandAbstract The mechanisms by which exercise benefits patients with non-alcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, remain poorly understood. A non-targeted liquid chromatography-mass spectrometry (LC–MS)-based metabolomics analysis was used to identify metabolic changes associated with NAFLD in humans upon exercise intervention (without diet change) across four different sample types—adipose tissue (AT), plasma, urine, and stool. Altogether, 46 subjects with NAFLD participated in this randomized controlled intervention study. The intervention group (n = 21) performed high-intensity interval training (HIIT) for 12 weeks while the control group (n = 25) kept their sedentary lifestyle. The participants' clinical parameters and metabolic profiles were compared between baseline and endpoint. HIIT significantly decreased fasting plasma glucose concentration (p = 0.027) and waist circumference (p = 0.028); and increased maximum oxygen consumption rate and maximum achieved workload (p < 0.001). HIIT resulted in sample-type-specific metabolite changes, including accumulation of amino acids and their derivatives in AT and plasma, while decreasing in urine and stool. Moreover, many of the metabolite level changes especially in the AT were correlated with the clinical parameters monitored during the intervention. In addition, certain lipids increased in plasma and decreased in the stool. Glyco-conjugated bile acids decreased in AT and urine. The 12-week HIIT exercise intervention has beneficial ameliorating effects in NAFLD subjects on a whole-body level, even without dietary changes and weight loss. The metabolomics analysis applied to the four different sample matrices provided an overall view on several metabolic pathways that had tissue-type specific changes after HIIT intervention in subjects with NAFLD. The results highlight especially the role of AT in responding to the HIIT challenge, and suggest that altered amino acid metabolism in AT might play a critical role in e.g. improving fasting plasma glucose concentration. Trial registration ClinicalTrials.gov (NCT03995056).https://doi.org/10.1038/s41598-022-10481-9 |
| spellingShingle | Ambrin Farizah Babu Susanne Csader Ville Männistö Milla-Maria Tauriainen Heikki Pentikäinen Kai Savonen Anton Klåvus Ville Koistinen Kati Hanhineva Ursula Schwab Effects of exercise on NAFLD using non-targeted metabolomics in adipose tissue, plasma, urine, and stool Scientific Reports |
| title | Effects of exercise on NAFLD using non-targeted metabolomics in adipose tissue, plasma, urine, and stool |
| title_full | Effects of exercise on NAFLD using non-targeted metabolomics in adipose tissue, plasma, urine, and stool |
| title_fullStr | Effects of exercise on NAFLD using non-targeted metabolomics in adipose tissue, plasma, urine, and stool |
| title_full_unstemmed | Effects of exercise on NAFLD using non-targeted metabolomics in adipose tissue, plasma, urine, and stool |
| title_short | Effects of exercise on NAFLD using non-targeted metabolomics in adipose tissue, plasma, urine, and stool |
| title_sort | effects of exercise on nafld using non targeted metabolomics in adipose tissue plasma urine and stool |
| url | https://doi.org/10.1038/s41598-022-10481-9 |
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