Exercise training adaptations in liver glycogen and glycerolipids require hepatic AMP-activated protein kinase in mice

Hughey, Curtis C.; Bracy, Deanna P.; Rome, Ferrol I.; Goelzer, Mickael; Donahue, E. Patrick; Viollet, Benoit; Foretz, Marc; Wasserman, David H.

doi:10.1152/ajpendo.00289.2023

Cited by 3 publications

(1 citation statement)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This information enumerates isotopomer and mass balances that detail the conservation of hydrogen and carbon atoms in the network. The reaction network used in this study has been thoroughly described ( 31 ) and used to quantify glucose and TCA cycle fluxes previously ( 29 , 34 – 36 ). After constraining flux through citrate synthase to an arbitrary value of 100, relative fluxes within the reaction network are estimated simultaneously by regressing the model in an iterative manner to fit the raw mass isotopomer data obtained from the glucose fragments.…”

Section: Methodsmentioning

confidence: 99%

Disruption of hepatic mitochondrial pyruvate and amino acid metabolism impairs gluconeogenesis and endurance exercise capacity in mice

Martino,

Habibi,

Ferguson

et al. 2024

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

View full text Add to dashboard Cite

Exercise robustly increases the glucose demands of skeletal muscle. This demand is met not only by muscle glycogenolysis, but also by accelerated liver glucose production from hepatic glycogenolysis and gluconeogenesis to fuel mechanical work and prevent hypoglycemia during exercise. Hepatic gluconeogenesis during exercise is dependent on highly coordinated responses within and between muscle and liver. Specifically, exercise increases the rate at which gluconeogenic precursors such as pyruvate/lactate or amino acids are delivered from muscle to the liver, extracted by the liver, and channeled into glucose. Herein, we examined the effects of interrupting gluconeogenic efficiency and capacity on exercise performance by deleting hepatic mitochondrial pyruvate carrier 2 (MPC2) and/or alanine transaminase 2 (ALT2) in mice. We found that deletion of MPC2 or ALT2 alone did not significantly affect time to exhaustion or post-exercise glucose concentrations in treadmill exercise tests, but mice lacking both MPC2 and ALT2 in liver (DKO) reached exhaustion faster and exhibited lower circulating glucose during and after exercise. Use of ²H/¹³C metabolic flux analyses demonstrated that DKO mice exhibited lower endogenous glucose production owing to decreased glycogenolysis and gluconeogenesis at rest and during exercise. The decreased gluconeogenesis was accompanied by lower anaplerotic, cataplerotic, and TCA cycle fluxes. Collectively, these findings demonstrate that the transition of the liver to the gluconeogenic mode is critical for preventing hypoglycemia and sustaining performance during exercise. The results also illustrate the need for interorgan crosstalk during exercise as described by the Cahill and Cori cycles.

show abstract

Section: Methodsmentioning

confidence: 99%

Disruption of hepatic mitochondrial pyruvate and amino acid metabolism impairs gluconeogenesis and endurance exercise capacity in mice

Martino,

Habibi,

Ferguson

et al. 2024

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

View full text Add to dashboard Cite

show abstract

Causal relationship analysis between 35 blood/urine metabolites and gastroesophageal reflux disease: A Mendelian randomization combined meta-analysis study

Chen,

Xu,

Wen

et al. 2024

Medicine

View full text Add to dashboard Cite

Gastroesophageal reflux disease (GERD) is a common condition worldwide. Despite numerous studies on GERD, the causal relationships between blood/urine metabolites and GERD remain unclear. This study aims to explore the causal relationships between GERD and 35 blood/urine metabolites. In this study, we conducted Mendelian randomization (MR) analyses for 35 blood/urine metabolites with GERD phenotypes from the FinnGen R10 and UKB databases separately. We then performed a meta-analysis of the inverse variance weighted results from the 2 MR analyses and applied multiple corrections to the significant P values from the meta-analysis. Finally, we conducted reverse causality validation for the corrected positive blood/urine metabolite phenotypes with GERD. After conducting MR analysis combined with meta-analysis and performing multiple corrections, we found significant positive causal associations between only 3 blood/urine metabolites and GERD, with no significant reverse associations. Among them, 2 are risk factors for the occurrence of GERD: alanine aminotransferase levels (odds ratio (OR) = 1.120, 95% confidence interval (CI) = 1.064–1.180, P = .0005) and urate levels (OR = 1.095, 95% CI = 1.044–1.147, P = .005). Additionally, sex hormone-binding globulin levels are protective against GERD (OR = 0.928, 95% CI = 0.896–0.961, P = .0009). Elevated levels of the metabolites alanine aminotransferase and urate are associated with an increased risk of GERD, identifying them as risk factors for the condition. In contrast, higher levels of SHBG are linked to a decreased risk of GERD, indicating that SHBG is a protective factor against the disease.

show abstract

Untargeted Metabolomics and Proteomics-based Research of the Long-term Exercise on Human Body

Zhuang,

Wang,

et al. 2024

Preprint

View full text Add to dashboard Cite

Regular long-term exercise can benefit the body and reduce the risk of several diseases, such as cardiovascular disease, diabetes, and obesity. The proteomic and metabolomic changes, as well as the physiological responses associated with long-term exercise, remain incompletely understood. To investigate the effects of long-term exercise on the human body, 14 subjects with long-term exercise habits and 10 subjects without exercise habits were selected for this study. Morning urine samples were collected and analyzed for untargeted metabolomics and proteomics using liquid chromatography-mass spectrometry. A total of 404 differential metabolites and 394 differential proteins were screened in this research, and the analysis results indicated that long-term exercise may affect energy metabolism, amino acid synthesis and metabolism, nucleotide metabolism, steroid hormone biosynthesis, and inflammatory response. These findings offer a more comprehensive understanding of the molecular effects of long-term exercise on the human body and provide a basis for future research exploring the underlying mechanisms.

show abstract

Exercise training adaptations in liver glycogen and glycerolipids require hepatic AMP-activated protein kinase in mice

Cited by 3 publications

References 77 publications

Disruption of hepatic mitochondrial pyruvate and amino acid metabolism impairs gluconeogenesis and endurance exercise capacity in mice

Disruption of hepatic mitochondrial pyruvate and amino acid metabolism impairs gluconeogenesis and endurance exercise capacity in mice

Causal relationship analysis between 35 blood/urine metabolites and gastroesophageal reflux disease: A Mendelian randomization combined meta-analysis study

Untargeted Metabolomics and Proteomics-based Research of the Long-term Exercise on Human Body

Contact Info

Product

Resources

About