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Hepatic Lipoprotein Export and Remission of Human Type 2 Diabetes after Weight Loss

Lookup NU author(s): Dr Ahmad Al-Mrabeh, Dr Sviatlana Zhyzhneuskaya, Dr Carl Peters, Alison Barnes, Shaden Melhem, Dr Kieren Hollingsworth, Professor Georg Lietz, Professor John Mathers, Dr Naweed Sattar, Professor Roy Taylor



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


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.

Publication metadata

Author(s): Al-Mrabeh A, Zhyzhneuskaya SV, Peters C, Barnes AC, Melhem S, Jesuthasan A, Aribasala B, Hollingsworth KG, Lietz G, Mathers JC, Sattar N, Lean MEJ, Taylor R

Publication type: Article

Publication status: Published

Journal: Cell Metabolism

Year: 2020

Volume: 31

Issue: 2

Pages: 233-249

Print publication date: 04/02/2020

Online publication date: 19/12/2019

Acceptance date: 25/11/2019

Date deposited: 20/02/2020

ISSN (print): 1550-4131

ISSN (electronic): 1932-7420

Publisher: Elsevier Inc


DOI: 10.1016/j.cmet.2019.11.018

PubMed id: 31866441


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Funder referenceFunder name
13/0004691Diabetes UK