Upper intestinal lipids trigger a gut-brain-liver axis to regulate glucose production (Nature, 2008, 452:1012-1016)

報告日期: 2008/10/28
報告時間: 15:10/16:00
報告學生: 郭力華(英文報告)
講評老師: 鄭瑞棠
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971028-1.pdf

Upper intestinal lipids trigger a gut-brain-liver axis to regulate glucose production

 

Nature 452, 1012-6 (24 April 2008)

 

Speaker: Li-Hua Kuo (郭力華)

Commentator: Dr. Juei-Tang Cheng (鄭瑞棠 老師)

Date: 10/28/2008 15:10~ 16:00

Place: Room 602

 

Abstract

Following meal intake, concentrations of insulin in plasma can appear higher than normal, because of substantially raised plasma glucose. Insulin secretion from the pancreas not only promotes glucose uptake into tissues but also suppresses production by the liver of glucose derived from stored fuels. However, it has been shown that as the first step of contact with ingested food, the gastrointestinal tract is positioned to initiate after-meal adaptations. Studies indicate that upper intestinal lipids inhibit food intake in rodents and humans by activation of an intestine-brain axis. In parallel, a brain-liver axis has been proposed to detect blood lipids to inhibit glucose production in rodents. Thus, the authors tested the hypothesis that upper intestinal lipids activate an intestine-brain-liver neural axis to regulate glucose homeostasis. First, the authors demonstrated the direct link between gut and liver by showing that lipid infusion in the upper intestine led to long-chain fatty acyl-coenzyme A (LCFA-CoA) production, which blocked liver-dependent glucose production in the pre-absorptive state. This effect was reversed by co-administration of lipids with the acyl-CoA synthetase inhibitor triacsin C, demonstrating that upper intestinal lipids regulate glucose homeostasis. Second, co-infusion of lipids with the anaesthetic tetracaine blunted the effect of intestinal lipids on liver glucose production. The same phenomenon was seen in either disconnection of the neural circuit between the gut and the brain or administration of neurotransmission blocker MK-801 into hindbrain. Finally, disconnection of the neural circuit between the brain and the liver disturbed the inhibitory effects of upper intestinal lipids on glucose homeostasis. Taken together, these results confirmed the relevance of the active communication among intestine, brain and liver to regulate glucose homeostasis, and thereby revealed a previously unknown pathway regulating glucose homeostasis.

 

Reference

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2. Beraza, N., Trautwein, C. The gut-brain-liver axis: a new option to treat obesity and diabetes? Hepatology. 48, 1011-3 (2008)