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)

Abstract

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
• Status: Published
• Refereed: Yes
• 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 > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Cell Metabolism
• Publisher: Elsevier (Cell Press)
• ISSN: 1550-4131
• 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
190677		Reversal 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 Lean	Diabetes UK (DIABETUK)	13/0004691	Med - Human Nutrition