Chenchen Xu1,2,3, Mariya Markova1,2, Nicole Seebeck1,2,4, Anne Loft2,5, Silke Hornemann1,2, Thomas Gantert1,2,4, Stefan Kabisch1,2,3, Kathleen Herz1,2, Jennifer Loske6, Mario Ost7, Verena Coleman4,7, Frederick Klauschen8,9, Anke Rosenthal10, Volker Lange11,12, Jürgen Machann2,13,14, Susanne Klaus4,7, Tilman Grune2,4,15,16,17, Stephan Herzig2,5, Olga Pivovarova-Ramich1,2,3,6, Andreas F H Pfeiffer1,2,3. 1. Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, Germany. 2. German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany. 3. Department of Endocrinology, Diabetes and Nutrition, Charité-Universitätsmedizin Berlin, Berlin, Germany. 4. Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany. 5. Department for Internal Medicine I and Clinical Chemistry, Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg and Joint Heidelberg-IDC Translational Diabetes Program, Heidelberg University Hospital, Heidelberg, Germany. 6. Research Group Molecular Nutritional Medicine, Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. 7. Department of Physiology of Energy Metabolism, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, Germany. 8. Institute of Pathology, Charité-Universitätsmedizin Berlin, Berlin, Germany. 9. German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany. 10. Clinic for Nutritional Medicine, Berlin, Germany. 11. Centre for Obesity and Metabolic Surgery, Vivantes Hospital, Berlin, Germany. 12. Helios Klinikum Berlin-Buch, Berlin, Germany. 13. Institute of Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, The University of Tübingen, Tübingen, Germany. 14. Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, Tübingen, Germany. 15. NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Nuthetal, Germany. 16. Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. 17. German Center for Cardiovascular Research (DZHK), Berlin, Germany.
Abstract
BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent and nutrition intervention remains the most important therapeutic approach for NAFLD. Our aim was to investigate whether low- (LP) or high-protein (HP) diets are more effective in reducing liver fat and reversing NAFLD and which mechanisms are involved. METHODS:19 participants with morbid obesity undergoing bariatric surgery were randomized into two hypocaloric (1500-1600 kcal/day) diet groups, a low protein (10E% protein) and a high protein (30E% protein), for three weeks prior to surgery. Intrahepatic lipid levels (IHL) and serum fibroblast growth factor 21 (FGF21) were measured before and after the dietary intervention. Autophagy flux, histology, mitochondrial activity and gene expression analyses were performed in liver samples collected during surgery. RESULTS:IHL levels decreased by 42.6% in the HP group, but were not significantly changed in the LP group despite similar weight loss. Hepatic autophagy flux and serum FGF21 increased by 66.7% and 42.2%, respectively, after 3 weeks in the LP group only. Expression levels of fat uptake and lipid biosynthesis genes were lower in the HP group compared with those in the LP group. RNA-seq analysis revealed lower activity of inflammatory pathways upon HP diet. Hepatic mitochondrial activity and expression of β-oxidation genes did not increase in the HP group. CONCLUSIONS:HP diet more effectively reduces hepatic fat than LP diet despite of lower autophagy and FGF21. Our data suggest that liver fat reduction upon HP diets result primarily from suppression of fat uptake and lipid biosynthesis.
RCT Entities:
BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent and nutrition intervention remains the most important therapeutic approach for NAFLD. Our aim was to investigate whether low- (LP) or high-protein (HP) diets are more effective in reducing liver fat and reversing NAFLD and which mechanisms are involved. METHODS: 19 participants with morbid obesity undergoing bariatric surgery were randomized into two hypocaloric (1500-1600 kcal/day) diet groups, a low protein (10E% protein) and a high protein (30E% protein), for three weeks prior to surgery. Intrahepatic lipid levels (IHL) and serum fibroblast growth factor 21 (FGF21) were measured before and after the dietary intervention. Autophagy flux, histology, mitochondrial activity and gene expression analyses were performed in liver samples collected during surgery. RESULTS: IHL levels decreased by 42.6% in the HP group, but were not significantly changed in the LP group despite similar weight loss. Hepatic autophagy flux and serum FGF21 increased by 66.7% and 42.2%, respectively, after 3 weeks in the LP group only. Expression levels of fat uptake and lipid biosynthesis genes were lower in the HP group compared with those in the LP group. RNA-seq analysis revealed lower activity of inflammatory pathways upon HP diet. Hepatic mitochondrial activity and expression of β-oxidation genes did not increase in the HP group. CONCLUSIONS: HP diet more effectively reduces hepatic fat than LP diet despite of lower autophagy and FGF21. Our data suggest that liver fat reduction upon HP diets result primarily from suppression of fat uptake and lipid biosynthesis.
Authors: Olga Pivovarova-Ramich; Jennifer Loske; Silke Hornemann; Mariya Markova; Nicole Seebeck; Anke Rosenthal; Frederick Klauschen; José Pedro Castro; René Buschow; Tilman Grune; Volker Lange; Natalia Rudovich; D Margriet Ouwens Journal: Cells Date: 2021-04-29 Impact factor: 6.600
Authors: Li Xu; Rita Schüler; Chenchen Xu; Nicole Seebeck; Mariya Markova; Veronica Murahovschi; Andreas F H Pfeiffer Journal: Ann Transl Med Date: 2020-12
Authors: Thomas M Barber; Petra Hanson; Stefan Kabisch; Andreas F H Pfeiffer; Martin O Weickert Journal: Nutrients Date: 2021-04-03 Impact factor: 5.717