Exercise Regulates the Metabolic Homeostasis of Methamphetamine Dependence

Abstract

Physical exercise is effective in enhancing cognitive function, reducing anxiety and depressive symptoms, reducing cravings, and improving quality of life in methamphetamine (METH) addiction. However, little is known about the effect of exercise on metabolic profiles. We performed LC/MS-based targeted metabolic profiling on serum samples to investigate the metabolic characteristics of METH dependence and find the differences between METH-dependent individuals and nonusers and evaluated the metabolomic profiles of individuals with METH dependence following aerobic exercise training. We identified a total of 201 metabolites, among which 115 were differentially expressed under METH use. Among the differentially regulated metabolites, 72 were selected as potential biomarkers. Further analysis identified 19 pathways, among which glyoxylate and dicarboxylate metabolism; alanine, aspartate, and glutamate metabolism; and citrate cycle were most significantly affected by METH. The aerobic exercise intervention differentially regulated 55 metabolites, of which 51 were selected as potential biomarkers and were mainly enriched in 10 pathways. Interestingly, alanine, aspartate, and glutamate metabolism and nitrogen metabolism were the remarkably affected pathways. Furthermore, METH increased the serum levels of glutamate and decreased GABA, whereas exercise decreased the serum levels of glutamate and increased GABA. Results suggested that METH dependency disturbed normal metabolic homeostasis, whereas exercise restored metabolism.

Mass Sportrometry: An annual look back at applications of mass spectrometry in sport and exercise science

“…Nonetheless, the authors claim the application of a multi‐metabolite profiling panel to be of use for investigating training load in runners. This wideband targeted approach was also identified in six additional studies over the past year 25,26,28,40,52,53 …”

“…In 2022, targeted analyses were the most commonly applied approach for MS-based research in SES, with 52 human participant studies published. These experiments were predominantly performed in plasma 6,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] or serum, [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] with other biosamples mediums utilized such as urine, [51][52][53][54][55] fecal matter, 56,57 breath gases, [58][59][60][61][62][63] red blood cells, …”

“…This wideband targeted approach was also identified in six additional studies over the past year. 25,26,28,40,52,53 In 2022, 18 studies used a traditional non-targeted metabolomics assay. 18,24,30,[83][84][85][86][87][88][89][90][91][92][93][94][95][96][97] Perhaps the most thought-provoking exercise metabolomics publication from 2022 came from the Long Lab at Stanford University and was published in Nature.…”

Effect of aerobic exercise on brain metabolite profiles in mice models of methamphetamine addiction: LC-MS-based metabolomics study

“…Currently, this emerging method can be used to identify changes in metabolites affected by addictive drugs [19]. Clinical studies have found that compared with non-drug users, MA abusers have disturbances in serum metabolism, including phenylalanine metabolism, glyoxylate and dicarboxylate metabolism, and alanine, aspartate and glutamate metabolism, which may partially explain the oxidative stress and neuroin ammatory changes induced by MA [31]. Furthermore, metabolomics studies based on magnetic resonance imaging and positron emission tomography suggested that brain volume is affected in MA-dependent individuals, and the major metabolites in brain tissue are abnormally represented, including N-acetylasparate and total creatine [32].…”

Effects of moderate-intensity exercise on social health and physical and mental health of methamphetamine-dependent individuals: A randomized controlled trial

“…Physical exercise is considered a potential treatment for MA addiction (25)(26)(27). And numerous mechanisms have been proposed to explain why exercise can improve the health of MA-dependent individuals, including the improvement of the nervous system, the improvement of the inhibitory control ability, the recovery of the monoaminergic system, the recovery of the blood-brain barrier, and the remodeling of cortical function (28)(29)(30)(31)(32).…”