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An Exercise-Inducible Metabolite that Suppresses Feeding and Obesity
from PCR - Fall 2022
Reporter Articles.
by Krish Patel (IV)
A study conducted by 29 scientists has uncovered the nature of an exercise-inducible metabolite that can help suppress feeding and obesity. The study concentrates on the metabolite N-lactoyl-phenylalanine (Lac-Phe), a signaling metabolite in the bloodstream that can offer protection against obesity. Although the study was conducted on mice, the presence of this metabolite has been found in a variety of mammals, from racehorses to humans. One of the fascinating functions of the LacPhe metabolite is its ability to improve glucose homeostasis, which can help prevent type 2 diabetes. For instance, in obese mice, mediated increases in Lac-Phe reduce food intake while having no affect on energy or movement. During the experiment, mice were first run on a treadmill until exhaustion, to simulate exercise. Then, the scientist performed both targeted and untargeted metabolomics (the study of metabolites within an organism) on the blood plasma of mice in order to collect the data in an unbiased manner. While the scientists noticed an increase in metabolites like lactate, they were surprised to see that the most significant change was found by the untargeted metabolomics. The chemical formula and mass to charge ratio only confirmed this, as it didn’t match any metabolite in their original list. This metabolite was assigned to a conjugate of lactate and phenylalanine also known as Lac-Phe. Plasma Lac-Phe levels in mice dramatically increased after their run and took 1 hour to return back to base levels. The scientists were able to conclude that the Lac-Phe metabolite is able to circulate best during exercise. However, scientists still needed to observe how the production of this metabolite suppresses obesity. After noticing that Lac-Phe is produced in Cnpd2 cells, the scientists used mice that had their Cndp2 cells removed. The two groups in this part of the experiment were the Wild Type mice (WT), and the CNDP2-KO which had no Cnpd2 cells. It was shown that after 40 days, the CNDP2-KO mice were on average 7 grams heavier, with most of the additional weight being in the tissue. Additionally, during exercise, WT mice had 3 times the Lac-Phe concentration when compared to the CNDP2KO, while the CNDP2-KO had a greater cumulative food intake. Therefore, Cnpd2 cells are the primary producers of the Lac-Phe metabolite and are equally as vital in suppressing obesity. In summation, this research proves that LacPhe, a metabolite in the bloodstream, is able to offer improved protection against obesity. Lac-Phe also allows for the subject to consume half as much food as it normally would after twelve hours. And without the Cnpd2 cell, there is a noticeable decrease in Lac-Phe production while tissue weight and food intake increase. The future of helping those who suffer from cardiometabolic diseases like obesity and type 2 diabetes may very well be down this avenue.
