Regulation of cephalic phase of insulin release and glucose homeostasis by food odor perception in heath and obesity / type 2 diabetes
Description: Obesity and type 2 diabetes (T2D) remain epidemic problems. Both diseases are known to reduce the quality of life and lead to serious complications such as cardiovascular events and microangiopathic alterations in the eyes, kidneys, and peripheral nerves. New strategies are awaited to regulate body metabolism by brain pathways. Over the last few years, the olfactory system has been shown to be a major regulator of metabolic control in rodents and humans, sending crucial information about food quality to the limbic system, including the hypothalamus. Indeed, smell strongly influences appetite, and anosmic patients suffer from problems in food intake. Cephalic phase responses in a fasted state are preabsorptive mechanisms such as salivation in preparation for the metabolic/glucose shoot during food intake. Among these responses, the cephalic phase of insulin release (CPIR) is defined as the insulin release before food intake (~10 min) when the sensory receptors are stimulated. Although CPIR has been repetitively demonstrated in humans, its role in the regulation of postprandial glucose homeostasis and the metabolic consequences of its dysfunction are still not fully understood in the context of health and obesity/Type 2 Diabetes. We have recently demonstrated the existence of an olfactory bulb (OB)-pancreas axis which mediates the food odor-evoked CPIR in the mouse. This pathway is regulated by food odors and mediated by Glucagon-like protein 1 (GLP-1) in the OB and is deficient in obese mice. “Smellins” aim is to characterize the regulatory power of the preprandial odor-induced CPIR on postprandial glucose homeostasis. Our goals are i) to decipher the role of GLP-1 in the OB of mice in postprandial energy processing, once CPIR has been triggered with food odors; ii) to investigate through a accurately-designed clinical investigation the role of odor-induced CPIR on postprandial glucose in obese subjects; iii) to test treatments including intranasal inhalation of GLP-1 analogs and bariatric surgery to recover odor-induced CPIR in obesity models. The outcome of this work is to provide, using sets of food odors to regulate CPIR, a solid evidence-based clinical and mechanistic understanding of the OB-pancreas axis and new non-invasive strategies to regulate food intake and glucose homeostasis in obesity and T2D.
Funder: Agence Nationale de la Recherche
Amount: €466,800
Funding type: research
Funder scheme: AAPG2024
Start date: 2025-03-01
Investigator: Hirac GURDEN
Institution: Université Paris Cité
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Funded outputs count: 0
Funder award ID: ANR-24-CE17-7944
OpenAlex ID: G109798806