Exercise heats up the hypothalamus to drive down food intake, according to a study publishing on April 24 in the open-access journal PLOS Biology by Jae Hoon Jeong, Young-Hwan Jo, and colleagues at the Albert Einstein College of Medicine in New York. The findings answer a long-standing question about the cause of exercise-induced reduction in appetite.
Short-term appetite suppression is a well-known consequence of vigorous exercise, but the physiological mechanism behind it has been unclear. One likely mediator of the effect is the hypothalamus, a region of the forebrain that integrates many different kinds of signals from the body, including hormones, nutrients, and temperature, to produce homeostatic responses such as feeding or food avoidance. Many of those responses are driven by cells of the hypothalamic arcuate nucleus, but these cells have not previously been shown to possess a key temperature sensor found elsewhere in the hypothalamus, called the TRPV1-like receptor (transient receptor potential vanilloid 1 receptor-like receptor).
The authors first showed that food-suppressing (anorexigenic) proopiomelanocortin (POMC) neurons in the arcuate nucleus express these receptors, using single-cell real-time PCR to demonstrate the presence of messenger RNA for the receptor, and immunohistochemistry to confirm the presence of the protein. Next, they showed that POMC neuron activity increased in response to a rise in temperature. This response could be prevented either by blocking the receptor with a chemical antagonist or preventing its expression through genetic means.
When capsaicin, a hot pepper extract that also activates the TRPV1-like receptor was administered into the arcuate nucleus, the mice reduced the amount of food they ate for up to 12 hours. This effect could be mitigated by blocking the receptor or preventing its expression before capsaicin administration. Finally, the authors showed that exercise increased the temperature in the arcuate nucleus within 20 minutes of the onset of exercise, and that temperature remained elevated for more than one hour. At the end of 40 minutes of exercise, mice spontaneously reduced their food intake by about 50% compared to non-exercised mice. Blocking the receptor or preventing its expression abolished this difference.
"Our results support the interpretation that arcuate nucleus cells of the hypothalamus have the ability to respond not only to hormones and nutrients, but also to temperature," Young-Hwan said. "We believe these cells are likely to play a role in suppressing food intake in response to exercise."
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Citation: Jeong JH, Lee DK, Liu S-M, Chua SC Jr, Schwartz GJ, Jo Y-H (2018) Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake. PLoS Biol 16(4): e2004399. https:/
Funding: NIDDK (grant number DK020541). received by Y-HJ, SC, and GS. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NIDDK (grant number DK092246). received by Y-HJ. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.