Hepatic lipoprotein export and remission of human type 2 diabetes after weight loss

Al-Mrabeh, A. et al. (2020) Hepatic lipoprotein export and remission of human type 2 diabetes after weight loss. Cell Metabolism, 31(2), 233-249.e4. (doi: 10.1016/j.cmet.2019.11.018) (PMID:31866441)

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The role of hepatic lipoprotein metabolism in diet-induced remission of type 2 diabetes is currently unclear. Here, we determined the contributions of hepatic VLDL1-triglyceride production rate and VLDL1-palmitic acid content to changes in intra-pancreatic fat and return of first phase insulin response in a subgroup of the Diabetes Remission Clinical Trial. Liver fat, VLDL1-triglyceride production, and intra-pancreatic fat decreased after weight loss and remained normalized after 24 months of remission. First-phase insulin response remained increased only in those maintaining diabetes remission. Compared with those in remission at 24 months, individuals who relapsed after initial remission had a greater rise in the content of VLDL1-triglyceride and VLDL1-palmitic acid, re-accumulated intra-pancreatic fat, and lost first-phase response by 24 months. Thus, we observed temporal relationships between VLDL1-triglyceride production, hepatic palmitic acid flux, intra-pancreatic fat, and β-cell function. Weight-related disordered fat metabolism appears to drive development and reversal of type 2 diabetes.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Lean, Professor Michael and Sattar, Professor Naveed
Creator Roles:
Sattar, N.Writing – review and editing, Funding acquisition, Supervision
Lean, M. E.J.Writing – review and editing, Funding acquisition, Supervision
Authors: Al-Mrabeh, A., Zhyzhneuskaya, S. V., Peters, C., Barnes, A. C., Melhem, S., Jesuthasan, A., Aribisala, B., Hollingsworth, K. G., Lietz, G., Mathers, J. C., Sattar, N., Lean, M. E.J., and Taylor, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Cell Metabolism
Publisher:Elsevier (Cell Press)
ISSN (Online):1932-7420
Published Online:19 December 2019
Copyright Holders:Copyright © 2019 Elsevier Inc.
First Published:First published in Cell Metabolism 31(2):233-249.e4
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190677Reversal of T2DM to normal glucose tolerance using non-surgical weight management with low-energy-liquid-diet and long-term maintenance, within routine NHS care.Michael LeanDiabetes UK (DIABETUK)13/0004691Med - Human Nutrition