Olive oil administered before carbohydrates elicits early glucagon and GLP-1 responses that act in a partially redundant manner and, with involvement of vagal pathways, slow gastric emptying and attenuate the early post-meal glucose.
Photo Credit: KyotoU / Daisuke Yabe
Scientific Frontline: Extended "At a Glance" Summary: Nutrient Sequencing
The Core Concept: Nutrient sequencing is a dietary strategy in which specific macronutrients, such as fats, are consumed prior to carbohydrates to moderate post-meal elevations in blood glucose.
Key Distinction/Mechanism: Unlike restrictive diets that eliminate food groups, nutrient sequencing merely changes the order of ingestion. Consuming fat, such as olive oil, before carbohydrates slows gastric emptying and triggers an early, coordinated hormonal and neural response that lowers post-meal blood glucose.
Major Frameworks/Components:
- Hormonal response: Ingestion of olive oil prior to glucose triggers the early secretion of glucagon, GIP, and GLP-1.
- Glucagon signaling: Typically known for raising blood glucose, glucagon acts in a partially redundant manner with GLP-1 to lower blood sugar during a fat preload.
- Vagal nerve pathways: Neural communication via the subdiaphragmatic vagus nerve contributes to delayed gastric emptying and the ensuing glucose-lowering response.
- Gastric emptying: The speed at which the stomach delivers glucose to the intestine is significantly slowed by the hormone-nerve response initiated by early fat intake.
Branch of Science: Endocrinology, Physiology, and Nutritional Science.
Future Application: This physiological explanation strengthens the clinical rationale for testing and prescribing simple, sustainable meal-sequencing strategies for human patients, including those with type 2 diabetes and severe insulin deficiency.
Why It Matters: Elevated post-meal blood glucose is a critical therapeutic target in diabetes management; identifying how nutrient order engages the gut-brain axis provides a practical, everyday dietary intervention that does not require restricting entire food groups.
In treating diabetes, post-meal elevation of glucose levels is an important therapeutic target. Existing clinical studies indicate that eating vegetables, protein, or fat before carbohydrates can moderate a post-meal rise in blood glucose, pointing to the potential of meal sequencing as a simple and sustainable dietary strategy.
Scientists have often attributed the benefits of this strategy to slower gastric emptying and greater secretion of incretin hormones, such as GLP-1, that decrease blood glucose levels. However, the roles that gut and pancreatic hormones, as well as neural pathways, play in this process have remained less understood. This motivated an international team of researchers to investigate how the timing of fat intake influences glucose levels, hormone secretion, and gastric emptying.
"Our group has long been interested in practical dietary approaches that people can continue in everyday life," says corresponding author Daisuke Yabe of Kyoto University. "Meal sequencing is appealing because it merely changes how a meal is eaten rather than requiring people to avoid entire food groups."
The team used mice in their investigation, first having the subjects fast overnight. The mice were then divided into three groups: one receiving water followed by glucose, another receiving olive oil followed by glucose 15 minutes later, and the final group receiving glucose followed by olive oil 15 minutes later. After feeding the mice accordingly, the researchers measured blood glucose, plasma insulin, glucagon, GIP, and GLP-1 levels. The team also gave the mice acetaminophen and estimated gastric emptying by measuring blood acetaminophen levels after oral administration.
The scientists then repeated this experiment in several other groups of mice, including those with type 2 diabetes and those lacking the GLP-1 receptor. Additional experiments also included inhibiting glucagon or GLP-1 signaling, performing bilateral subdiaphragmatic vagus nerve ligation, and testing other dietary fats to confirm that responses were not specific to olive oil.
These test results revealed that giving mice olive oil before rather than after glucose reduced an early rise in blood glucose levels and slowed gastric emptying. Consuming fats before glucose also increased the early secretion of glucagon, GIP, and GLP-1, and all of these beneficial effects were retained in mice with type 2 diabetes and severe insulin deficiency.
The researchers observed that inhibiting either glucagon or GLP-1 signaling alone did not attenuate the glucose-lowering effect of the olive oil preload, whereas combined inhibition did. Furthermore, glucagon signaling, which is best known for raising blood glucose, also contributes to the glucose-lowering response of an olive oil preload in mice. The experiments involving vagus nerve ligation also suggested that vagal pathways contribute to these responses.
By providing a physiological explanation for the influence of nutrient order on post-meal glucose levels, this study strengthens the rationale for testing practical meal-sequencing strategies in people with and without diabetes.
"Our findings suggest that the order in which nutrients reach the gut can engage a coordinated hormone-nerve response that changes how quickly the stomach delivers glucose to the intestine," says Yabe.
Published in journal: Diabetes
Authors: Yanyan Liu, Hiromi Tsuchida, Sodai Kubota, Saki Kubota-Okamoto, Takehiro Kato, Yukio Horikawa, Shin Tsunekawa, Hitoshi Kuwata, Yuuka Fujiwara, Yuji Yamazaki, Yuichiro Yamada, Hiroki Fujita, Katsumi Iizuka, Naoya Murao, Shinji Ueno, Yusuke Seino, Atsushi Suzuki, Yoshitaka Hayashi, Tsuyoshi Nakanishi, Daniel J. Drucker, Takahiko Shiina, Yasutake Shimizu, Yusaku Iwasaki, Toshihiko Yada, Yohei Seno, Yuya Takahashi, Toshinori Imaizumi, Takaaki Murakami, Michael Horowitz, Yutaka Seino, and Daisuke Yabe
Source/Credit: Kyoto University
Edited by: Scientific Frontline
Reference Number: bio100926_01
