Biomedical subjects

John P Thyfault

Publications and source records attributed to John P Thyfault.

14 recordsLinked to original sources

PubMed2026

A combined stimulus of acute fasting and exercise modulates hippocampal mitochondrial quality control in healthy mice.

BACKGROUND AND AIMS: Exercise and fasting are recognized for their ability to improve brain health and mitigate neurodegeneration. However, little is known about how these interventions acutely impact mitochondrial quality control mechanisms including mitophagy. METHODS: We examined the effects of a single bout of fasting and exercise (FEx) on hippocampal mitochondrial function and proteomic remodeling in male and female mice. To assess in vivo autophagy dynamics, we combined proteomics with chloroquine (CQ) inhibition of autophagic flux. Mice were assigned to sedentary (Sed), fasting (F), exercise (Ex), or combined FEx groups and received unilateral intrahippocampal injections of CQ or PBS following treatments. Four hours later, hippocampi were collected for analysis. RESULTS: LC3-II levels significantly increased in the FEx group only following CQ treatment, indicating enhanced autophagic flux. Proteomic profiling showed sedentary males failed to mount a robust response to FEx however females exhibited upregulation of proteins involved in the TCA cycle, glutathione metabolism, and oxidative phosphorylation, suggesting greater mitochondrial adaptability. Functional assays supported these findings, females showed increased complex IV activity post-FEx. The mitochondrial DNA / nuclear DNA ratio increased after FEx regardless of sex, and upstream regulator analysis predicted activation of mitochondrial biogenesis. CONCLUSIONS: Together, these data reveal sex-specific mitochondrial remodeling in response to acute fasting and exercise. Defining these normative responses is critical for understanding how mitochondrial adaptability shapes resilience or vulnerability to neurological challenges.

Animals↗

PubMed2026

Hepatic ketogenic insufficiency blunts exercise-induced energy expenditure and alters mitochondrial proteins in skeletal muscle.

Ketone body (KB) utilization increases during fasting and exercise due to enhanced hepatic fatty acid oxidation and KB production via the rate-limiting mitochondrial enzyme hydroxymethylglutaryl-CoA synthase (HMGCS2). Since KB metabolism intersects with multiple metabolic pathways and skeletal muscle KB catabolism rises during exercise, we tested the hypothesis that liver-specific HMGCS2 knockouts (KO) would have reduced energy expenditure (EE) and changes in the mitochondrial proteome of skeletal muscle with chronic exercise through voluntary wheel running (VWR), time-restricted feeding (TRF), or both combined to boost hepatic KB production and utilization. Control (CON) and HMGCS2 knockout (KO) mice (n = 6-8 per group) underwent sedentary ad libitum feeding (SED + AL), SED + TRF, VWR + AL, and VWR + TRF for 16 wk, with whole body EE measured using indirect calorimetry. In CON mice, VWR increased total EE by 19.5% and nonresting EE by 50% under AL conditions, and total EE by 16% and nonresting EE by 47.9% under TRF conditions. However, the EE increases seen with VWR did not occur in KO mice. Proteomic analysis revealed that the loss of liver HMGCS2 significantly impacted proteins involved in metabolic processes within skeletal muscle, including reduced oxidative phosphorylation (OXPHOS) protein expression in SED KO mice compared with sedentary CON. Notably, VWR restored OXPHOS protein expression in the muscle of the liver HMGCS2 KO but did not alter it in the CON. Furthermore, muscle from liver HMGCS2 KO mice had elevated expression of glycolytic pathways in sedentary and VWR conditions. These results indicate that hepatic ketogenic deficiency (HMGCS2 KO) diminishes exercise-induced increases in EE and uniquely impacts baseline and exercise-related adaptations in the metabolic and mitochondrial proteome of skeletal muscle.

Hydroxymethylglutaryl-CoA Synthase↗

PubMed2025

A consensus guide to preclinical indirect calorimetry experiments.

Understanding the complex factors influencing mammalian metabolism and body weight homeostasis is a long-standing challenge requiring knowledge of energy intake, absorption and expenditure. Using measurements of respiratory gas exchange, indirect calorimetry can provide non-invasive estimates of whole-body energy expenditure. However, inconsistent measurement units and flawed data normalization methods have slowed progress in this field. This guide aims to establish consensus standards to unify indirect calorimetry experiments and their analysis for more consistent, meaningful and reproducible results. By establishing community-driven standards, we hope to facilitate data comparison across research datasets. This advance will allow the creation of an in-depth, machine-readable data repository built on shared standards. This overdue initiative stands to markedly improve the accuracy and depth of efforts to interrogate mammalian metabolism. Data sharing according to established best practices will also accelerate the translation of basic findings into clinical applications for metabolic diseases afflicting global populations.

Calorimetry, Indirect↗

PubMed2006

Inactivity induces increases in abdominal fat.

Previously, inducing inactivity for 53 h after 21 days of voluntary running resulted in a 25 and 48% increase in epididymal and omental fat pad weights, respectively, while rats continued to eat more than a group that never had access to a running wheel (J Physiol 565: 911-925, 2005). We wanted to test the hypothesis that inactivity, independent of excessive caloric intake, could induce an increase in fat pad mass. Twenty-one-day-old rats were given access to voluntary running wheels for 42-43 days so that they were running approximately 9 km/day in the last week of running, after which wheels were locked for 5, 53, or 173 h (WL5, WL53, WL173) before the rats were killed. During the 53 and 173 h of inactivity, one group of animals was pair fed (PF) to match sedentary controls, whereas the other continued to eat ad libitum (AL). Epididymal and retroperitoneal fat masses were significantly increased in the WL173-PF vs. the WL5 group, whereas epididymal, perirenal, and retroperitoneal fat masses were all significantly increased in the WL173-AL group compared with the WL5 group. Additionally, hyperplasia, and not hypertrophy, of the epididymal fat mass was responsible for the increase at WL173-AL as demonstrated by a significant increase in cell number vs. WL5, with no change in cell diameter or volume. Thus two important findings have been elucidated: 1) increases in measured abdominal fat masses occur in both AL and PF groups at WL173, and 2) adipocyte expansion via hyperplasia occurred with an ad libitum diet following cessation of voluntary running.

Abdomen↗

PubMed2006

Contraction of insulin-resistant muscle normalizes insulin action in association with increased mitochondrial activity and fatty acid catabolism.

Acute exercise can reverse muscle insulin resistance, but the mechanism(s) of action are unknown. With the use of a hindlimb perfusion model, we have found that acute contraction restores insulin-stimulated glucose uptake in muscle of obese Zucker rats to levels witnessed in lean controls. Previous reports have suggested that obesity-related insulin resistance stems from lipid oversupply and tissue accumulation of toxic lipid intermediates that impair insulin signaling. We reasoned that contraction might activate hydrolysis and oxidation of intramuscular lipids, thus alleviating "lipotoxicity" and priming the muscle for enhanced insulin action. Indeed, analysis of mitochondrial-derived acyl-carnitine esters suggested that contraction caused robust increases in beta-oxidative flux and mitochondrial oxidation. As predicted, contraction decreased intramuscular triacylglycerol content; however, diacylglycerol and long chain acyl-CoAs, lipid intermediates presumed to trigger insulin resistance, were either unchanged or increased. In muscles from obese animals, insulin-stimulated tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 remained impaired after contraction, whereas phosphorylation of the downstream signaling protein, AS160, was partially restored. These results suggest that acute exercise enables diabetic muscle to circumvent upstream defects in insulin signal transduction via mechanisms that are more tightly coupled to increased mitochondrial energy metabolism than the lowering of diacylglycerol and long chain acyl-CoA.

AMP-Activated Protein Kinases↗

PubMed2005

Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans.

Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and accumulation of intramyocellular triacylglycerol, but the underlying cause of these perturbations are yet unknown. Herein, we show that the lipogenic gene, stearoyl-CoA desaturase 1 (SCD1), is robustly up-regulated in skeletal muscle from extremely obese humans. High expression and activity of SCD1, an enzyme that catalyzes the synthesis of monounsaturated fatty acids, corresponded with low rates of fatty acid oxidation, increased triacylglycerol synthesis and increased monounsaturation of muscle lipids. Elevated SCD1 expression and abnormal lipid partitioning were retained in primary skeletal myocytes derived from obese compared to lean donors, implying that these traits might be driven by epigenetic and/or heritable mechanisms. Overexpression of human SCD1 in myotubes from lean subjects was sufficient to mimic the obese phenotype. These results suggest that elevated expression of SCD1 in skeletal muscle contributes to abnormal lipid metabolism and progression of obesity.

Body Mass Index↗

PubMed2005

Gestational diabetes is associated with depressed adiponectin levels.

OBJECTIVE: Adiponectin is a 29-kd adipocyte-secreted protein that has been linked to insulin resistance in obesity and diabetes. The aim of the present study was to evaluate adiponectin levels in the insulin-resistant state of diabetes in gestation. METHODS: Term, gravid subjects with diabetes (n = 31; age, 30.0 +/- 0.9 years; weight, 98.8 +/- 4.6 kg) and healthy, term, gravid subjects (n = 27; age, 26.1 +/- 1.1 years; weight, 91.2 +/- 3.78 kg) were examined. The diabetes group consisted of 11 class A1, 11 class A2, and nine class B subjects. Plasma insulin, glucose, adiponectin, and leptin were measured on samples obtained immediately before Cesarean or vaginal delivery. Data were presented as means +/- SE, and significance is set at P < or = .05. RESULTS: We observed decreased adiponectin levels in class A2 (4.93 +/- 0.58 microg/mL; P = .013) and class B diabetics (3.33 +/- 0.56 microg/mL; P = .001) as compared to controls (8.17 +/- 0.82 microg/mL), while a nonsignificant decrease was also observed in class A1 (6.58 +/- 1.13 microg/mL; P = .213). When grouping all gravid subjects, we observed that non-Caucasian subjects (n = 42) (5.51 +/- 0.51 microg/mL; P = .003) had lower adiponectin levels than Caucasian subjects (n = 16) (8.88 +/- 1.11 microg/mL). Within the non-Caucasian group, we found significantly lower adiponectin levels in diabetic gravid subjects (class A2: 4.24 +/- 0.75 microg/mL; P = .044; and class B: 3.33 +/- 0.56 microg/mL; P = .005) compared with nondiabetic gravid subjects (7.05 +/- 0.80 microg/mL). CONCLUSION: Class A2 and B gestational diabetes are associated with suppressed levels of adiponectin, similar to that found in other insulin-resistant states (type II diabetes and obesity).

Adiponectin↗

PubMed2005

Rest-interval length affects leukocyte levels during heavy resistance exercise.

We sought to determine the effect of varying rest intervals on leukocyte levels during heavy resistance exercise. Nine college men completed 2 exercise bouts of 10 sets of 10 repetitions at 65% 1 repetition maximum (1RM) leg press with 1- (1MIN) or 3-minute (3MIN) rest intervals, respectively. Blood collected at rest (PRE), immediately postexercise (POST), and 1.5 hours postexercise (1.5H) was analyzed for leukocyte levels. Data were analyzed using a 2 x 3 repeated measures analysis of variance. A greater PRE-POST lymphocytosis (+83% vs. +16%, p = 0.002) and monocytosis (+47% vs. +15%, p = 0.005) was observed following 1MIN vs. 3MIN. Serum creatine kinase (CK) activity was increased to a greater extent 24 h postexercise following the 1-minute rest protocol (p = 0.022). CK was correlated (r = 0.611) to the PRE-POST lymphocytosis. We conclude that short rest intervals increase the extent of postexercise lymphocytosis and monocytosis, when total work is kept constant.

Adult↗

PubMed2004

Impaired plasma fatty acid oxidation in extremely obese women.

Skeletal muscle from extremely obese individuals exhibits decreased lipid oxidation compared with muscle from lean controls. It is unknown whether this effect is observed in vivo or whether the phenotype is preserved after massive weight loss. The objective of this study was to compare free fatty acid (FFA) oxidation during rest and exercise in female subjects who were either lean [n = 7; body mass index (BMI) = 22.6 +/- 2.2 kg/m(2)] or extremely obese (n = 10; BMI = 40.8 +/- 5.4 kg/m(2)) or postgastric bypass patients who had lost >45 kg (weight reduced) (n = 6; BMI = 33.7 +/- 9.9 kg/m(2)) with the use of tracer ([(13)C]palmitate and [(14)C]acetate) methodology and indirect calorimetry. The lean group oxidized significantly more plasma FFA, as measured by percent fatty acid uptake oxidized, than the extremely obese or weight-reduced group during rest (66.6 +/- 14.9 vs. 41.5 +/- 16.4 vs. 39.9 +/- 15.3%) and exercise (86.3 +/- 11.9 vs. 56.3 +/- 22.1 vs. 57.3 +/- 20.3%, respectively). BMI significantly correlated with percent uptake oxidized during both rest (r = -0.455) and exercise (r = -0.459). In conclusion, extremely obese women and weight-reduced women both possess inherent defects in plasma FFA oxidation, which may play a role in massive weight gain and associated comorbidities.

Adult↗

PubMed2004

Pinitol supplementation does not affect insulin-mediated glucose metabolism and muscle insulin receptor content and phosphorylation in older humans.

This study assessed the effect of oral pinitol supplementation on oral and intravenous glucose tolerances and on skeletal muscle insulin receptor content and phosphorylation in older people. Fifteen people (6 men, 9 women; age 66 +/- 8 y; BMI 27.9 +/- 3.3 kg/m(2); hemoglobin A1c 5.39 +/- 0.46%, mean +/- SD) completed a 7-wk protocol. Subjects were randomly assigned to groups that during wk 2-7 consumed twice daily either a non-nutritive beverage (Placebo group, n = 8) or the same beverage with 1000 mg pinitol dissolved into it (Pinitol group, n = 7, total dose = 2000 mg pinitol/d). Testing was done at wk 1 and wk 7. In the Pinitol group with supplementation, 24-h urinary pinitol excretion increased 17-fold. The fasting concentrations of glucose, insulin, and C-peptide, and the 180-min area under the curve for these compounds, in response to oral (75 g) and intravenous (300 mg/kg) glucose tolerance challenges, were unchanged from wk 1 to wk 7 and were not influenced by pinitol. Also, pinitol did not affect indices of hepatic and whole-body insulin sensitivity from the oral glucose tolerance test and indices of insulin sensitivity, acute insulin response to glucose, and glucose effectiveness from the intravenous glucose tolerance test, estimated using minimal modeling. Pinitol did not differentially affect total insulin receptor content and insulin receptor phosphotyrosine 1158 and insulin receptor phosphotyrosine 1162/1163 activation in vastus lateralis samples taken during an oral-glucose-induced hyperglycemic and hyperinsulinemic state. These data suggest that pinitol supplementation does not influence whole-body insulin-mediated glucose metabolism and muscle insulin receptor content and phosphorylation in nondiabetic, older people.

Aged↗

PubMed2004

Postprandial metabolism in resistance-trained versus sedentary males.

INTRODUCTION: This investigation examined if postprandial metabolism differed between resistance-trained [(RT), N = 12] and sedentary [(SED), N = 12] males. A secondary objective was to determine whether different resistance-training programs [bodybuilding (BB), N = 8 and power/weight-lifting (PL), N = 8] resulted in disparate effects on postprandial energy metabolism. METHODS: Moderate fat [(MF), 37% carbohydrate, 18% protein, and 45% fat] and high carbohydrate [(HC), 79% carbohydrate, 20% protein, and 1% fat] meals were randomly administered, and postprandial metabolism was measured for 240 min. Carbohydrate oxidation, fat oxidation, diet-induced thermogenesis (DIT), and glucose and insulin areas under the curve (AUC) were calculated. RESULTS: Fat oxidization/lean body mass (LBM) was significantly greater in SED after the HC (RT, 0.27 +/- 0.02 g vs SED, 0.33 +/- 0.02 g, P = 0.017) and MF (RT, 0.34 +/- 0.02 g vs SED, 0.39 +/- 0.02 g, P = 0.036) meals. Carbohydrate oxidation/LBM was significantly greater in RT after the HC meal (RT, 0.87 +/- 0.03 g vs SED, 0.74 +/- 0.04 g, P = 0.017) only. DIT and DIT/LBM were significantly greater in RT compared with SED after the HC meal (DIT: RT, 351 +/- 21 kJ vs SED, 231 +/- 23 kJ, P = 0.001; DIT/LBM: RT, 5.25 +/- 0.028 kJ vs SED, 3.92 +/- 0.37 kJ, P = 0.009). The AUC for both glucose and insulin were significantly greater in SED compared with RT in response to the HC meal but not the MF meal. There were no differences in the BB and PL groups for any measured variables in response to either the HC or MF meals. CONCLUSION: These data indicate that postprandial metabolism is different between resistance-trained and sedentary males but that no such differences exist with different resistance training styles.

Adult↗

PubMed2004

Effects of liquid carbohydrate ingestion on markers of anabolism following high-intensity resistance exercise.

We examined the effects of liquid carbohydrate (CHO) supplementation on markers of anabolism following high-intensity resistance exercise. Nine resistance-trained men consumed either CHO or placebo (PLC) 10 minutes before and immediately following 2 resistance exercise sessions. Cortisol (CORT), insulin (INS), ammonia (AMM), and glucose (GLU) were measured before, immediately after, and 1.5 and 4 hours after exercise. Urinary nitrogen (NH(+3)) was measured 24 hours before and after exercise. There was a significant difference in INS levels immediately after exercise and 1.5 hours after exercise. No significant differences were observed for CORT, AMM, GLU, or NH(+3)between treatments. Significant within-group differences were found for the PLC group: CORT before compared with immediately after exercise; INS before compared with immediately after exercise and before compared with 1.5 hours after exercise; and AMM before compared with immediately after exercise and before compared with 1.5 hours after exercise. Significant within-group differences were found for the CHO group: CORT immediately after compared with 1.5 hours after exercise and immediately after compared with 4 hours after exercise; INS before compared with 1.5 hours after exercise; and AMM before compared with immediately after exercise. Liquid CHO ingestion leads to a more favorable anabolic environment immediately following a resistance exercise bout; however, our indirect measures of protein degradation were not altered by CHO ingestion.

Adult↗

PubMed2003

Effects of plyometric training and recovery on vertical jump performance and anaerobic power.

We examined the effects of 2 plyometric training programs, equalized for training volume, followed by a 4-week recovery period of no plyometric training on anaerobic power and vertical jump performance. Physically active, college-aged men were randomly assigned to either a 4-week (n = 19, weight = 73.4 +/- 7.5 kg) or a 7-week (n = 19, weight = 80.1 +/- 12.5 kg) program. Vertical jump height, vertical jump power, and anaerobic power via the Margaria staircase test were measured pretraining (PRE), immediately posttraining (POST), and 4 weeks posttraining (POST-4). Vertical jump height decreased in the 4-week group PRE (67.8 +/- 7.9 cm) to POST (65.4 +/- 7.8 cm). Vertical jump height increased from PRE to POST-4 in 4-week (67.8 +/- 7.9 to 69.7 +/- 7.6 cm) and 7-week (64.6 +/- 6.2 to 67.2 +/- 7.6 cm) training programs. Vertical jump power decreased in the 4-week group from PRE (8,660.0 +/- 546.5 W) to POST (8,541.6 +/- 557.4 W) with no change in the 7-week group. Vertical jump power increased PRE to POST-4 in 4-week (8,660.0 +/- 546.5 W to 8,793.6 +/- 541.4 W) and 7-week (8,702.8 +/- 527.4 W to 8,931.5 +/- 537.6 W) training programs. Anaerobic power improved in the 7-week group from PRE (1,121.9 +/- 174.7 W) to POST (1,192.2 +/- 189.1 W) but not the 4-week group. Anaerobic power significantly improved PRE to POST-4 in both groups. There were no significant differences between the 2 training groups. Four-week and 7-week plyometric programs are equally effective for improving vertical jump height, vertical jump power, and anaerobic power when followed by a 4-week recovery period. However, a 4-week program may not be as effective as a 7-week program if the recovery period is not employed.

Analysis of Variance↗

PubMed2003

Effects of effervescent creatine, ribose, and glutamine supplementation on muscular strength, muscular endurance, and body composition.

The purpose of this study was to examine the effects of a combination of effervescent creatine, ribose, and glutamine on muscular strength (MS), muscular endurance (ME) and body composition (BC) in resistance-trained men. Subjects were 28 men (age: 22.3 +/- 1.7 years; weight: 85.8 +/- 12.1 kg; height: 1.8 +/- 0.1 m) who had 2 or more years of resistance-training experience. A double blind, randomized trial was completed involving supplementation or placebo control and a progressive resistance-training program for 8 weeks. Dependent measures were assessed at baseline and after 8 weeks of resistance training. Both groups significantly improved MS and ME while the supplement group significantly increased body weight and fat-free mass. Control decreased body fat and increased fat-free mass. This study demonstrated that the supplement group did not enhance MS, ME, or BC significantly more than control after an 8-week resistance-training program.

Adult↗