Hepatic Lipoprotein Export and Remission of Human Type 2 Diabetes after Weight Loss
Ahmad Al-Mrabeh Cell Metab December 19, 2019
Highlights
• Remission of type 2 diabetes is associated with a major fall in liver fat export
• Re-emergence is associated with increased liver-derived plasma triglycerides
• These changes are reflected by intra-pancreatic fat content
• Beta-cell dysfunction is related to raised intra-pancreatic fat
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.
