医学创新论坛

（第010期）

Title: Gut-brain circuits for fat preference and immunity

Speaker: Meng-Tong Li （李梦彤）

                Postdoctoral Fellow

                Zuckerman Institute, Columbia University

Host：Lin Mei

           Chinese Institutes for Medical Research, Beijing

Time：10:00-11:30 a.m., Nov. 16, 2023 (Thursday)

Location: Room 1322, North Tower, Basic Research Building, Capital Medical University (首都医科大学基础科研楼北楼1322会议室)

Abstract：

The body-brain axis is emerging as a principal conductor of organismal physiology.  It senses and controls organ function, metabolism and nutritional state. Previously we revealed a gut-to-brain, post-ingestive intestinal sugar-sensing pathway driving craving and attraction to sugar. Here, focusing on fat preference, we show that fat stimuli can induce behavioral attraction even without a functional taste system via the gut-brain axis to drive preference for fat. Using single-cell data, we identified the vagal neurons responding to intestinal delivery of fat, and showed that genetic silencing of this gut-to-brain circuit abolished the development of fat preference. Finally, we identified the receptors and validated their role as the mediators of gut-to-brain fat-evoked responses.

Beyond nutrient preferences, the body-brain axis also plays a vital role in orchestrating immune responses. We discovered a body-to-brain neural circuit informing the brain of an emerging inflammatory response. Pro- and anti-inflammatory cytokines communicate with distinct populations of vagal neurons to tell the brain of an emerging inflammatory response. Genetic silencing of this body-to-brain circuit produced unregulated and out-of-control inflammatory responses while activation of this circuit afforded exceptional neural control of immune responses. Using single-cell RNA sequencing and functional imaging, to identify the circuit components of this neuro-immune axis, we showed that its selective manipulation can effectively suppress the pro-inflammatory response while enhancing an anti-inflammatory state, offering possibilities for immune disorder modulation.

The intertwined discoveries related to both the gut-brain circuits involved in nutrient preferences, such as fat preference, and the body-brain circuit controlling immune responses highlight the complexity and integrative nature of the body-brain axis. Understanding and harnessing these connections offer promising avenues for developing interventions that target multiple aspects of physiological health, from metabolic well-being to immune system regulation.

Reference:

Li M, Tan HE, Lu Z, Tsang KS, Chung AJ, Zuker CS. Gut-brain circuits for fat preference. Nature. 2022, 610(7933): 722-730. DOI: 10.1038/s41586-022-05266-z.