Biomedical subjects

Ronald N Cortright

Publications and source records attributed to Ronald N Cortright.

9 recordsLinked to original sources

PubMed2006

Decreased brown adipocyte recruitment and thermogenic capacity in mice with impaired peroxisome proliferator-activated receptor (P465L PPARgamma) function.

Mice with a dominant-negative peroxisome proliferator-activated receptor gamma (PPARgamma) mutation (P465L) unexpectedly had normal amounts of adipose tissue. Here, we investigate the adipose tissue of the PPARgamma P465L mouse in detail. Microscopic analysis of interscapular adipose tissue of P465L PPARgamma mice revealed brown adipocytes with larger unilocular lipid droplets, indicative of reduced thermogenic capacity. Under conditions of cold exposure, the brown adipose tissue of the PPARgamma P465L mice was less active, a fact reflected in decreased uncoupling protein 1 levels. Analysis of the white adipocytes confirmed their normal cytoarchitecture and development, yet classical white adipose depots of the P465L PPARgamma mice had a striking reduction in brown adipocyte recruitment, a finding supported by reduced expression of UCP1 in the perigonadal adipose depot. Taken together, these data suggest that whole animal impairment of PPARgamma alters the cellular composition of the adipose organ to a more "white" adipose phenotype. Physiologically, this impairment in brown adipocyte recruitment is associated with decreased nonshivering thermogenic capacity after cold acclimation as revealed by norepinephrine responsiveness. Our results indicate that maintenance of oxidative brown-like adipose tissue is more dependent on PPARgamma function for development than white adipose tissue, an observation that may be relevant when considering PPARgamma-dependent strategies for the treatment of obesity.

Acclimatization↗

PubMed2006

Skeletal muscle fat oxidation is increased in African-American and white women after 10 days of endurance exercise training.

OBJECTIVE: Obesity is associated with lower rates of skeletal muscle fatty acid oxidation (FAO), which is linked to insulin resistance. FAO is reduced further in obese African-American (AAW) vs. white women (CW) and may also be lower in lean AAW vs. CW. In lean CW, endurance exercise training (EET) elevates the oxidative capacity of skeletal muscle. Therefore, we determined whether EET would elevate skeletal muscle FAO similarly in AAW and CW with a lower lipid oxidative capacity. RESEARCH METHODS AND PROCEDURES: In vitro rates of FAO were assessed in rectus abdominus muscle strips using [1- 14C] palmitate (Pal) from lean AAW [BMI = 24.2 +/- 0.9 (standard error) kg/m2] and CW (23.6 +/- 0.8 kg/m2) undergoing voluntary abdominal surgery. Lean AAW (22 +/- 0.9 kg/m(2)) and CW (24 +/- 0.8 kg/m2) and obese AAW (36 +/- 1.2 kg/m2) and CW (40 +/- 1.3 kg/m2) underwent 10 consecutive days of EET on a cycle ergometer (60 min/d, 75% peak oxygen uptake). FAO was measured in vastus lateralis homogenates as captured 14CO2 using [1- 14C] Pal, palmitoyl-CoA (Pal-CoA), and palmityl-carnitine (Pal-Car). RESULTS: Muscle strip experiments showed suppressed rates of FAO (p = 0.03) in lean AAW vs. CW. EET increased the rates of skeletal muscle Pal oxidation (p = 0.05) in both lean AAW and CW. In obese subjects, Pre-EET Pal (but not Pal-CoA or Pal-Car) oxidation was lower (p = 0.05) in AAW vs. CW. EET increased Pal oxidation 100% in obese AAW (p < 0.05) and 59% (p < 0.05) in obese CW. Similar increases (p < 0.05) in post-EET FAO were observed for Pal-CoA and Pal-Car in both groups. DISCUSSION: Both lean and obese AAW possess a lower capacity for skeletal muscle FAO, but EET increases FAO similarly in both AAW and CW. These data suggest the use of EET for treatment against obesity and diabetes for both AAW and CW.

Adult↗

PubMed2005

Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism.

Skeletal muscle contains two populations of mitochondria that appear to be differentially affected by disease and exercise training. It remains unclear how these mitochondrial subpopulations contribute to fiber type-related and/or training-induced changes in fatty acid oxidation and regulation of carnitine palmitoyltransferase-1beta (CPT1beta), the enzyme that controls mitochondrial fatty acid uptake in skeletal muscle. To this end, we found that fatty acid oxidation rates were 8.9-fold higher in subsarcolemmal mitochondria (SS) and 5.3-fold higher in intermyofibrillar mitochondria (IMF) that were isolated from red gastrocnemius (RG) compared with white gastrocnemius (WG) muscle, respectively. Malonyl-CoA (10 muM), a potent inhibitor of CPT1beta, completely abolished fatty acid oxidation in SS and IMF mitochondria from WG, whereas oxidation rates in the corresponding fractions from RG were inhibited only 89% and 60%, respectively. Endurance training also elicited mitochondrial adaptations that resulted in enhanced fatty acid oxidation capacity. Ten weeks of treadmill running differentially increased palmitate oxidation rates 100% and 46% in SS and IMF mitochondria, respectively. In SS mitochondria, elevated fatty acid oxidation rates were accompanied by a 48% increase in citrate synthase activity but no change in CPT1 activity. Nonlinear regression analyses of mitochondrial fatty acid oxidation rates in the presence of 0-100 muM malonyl-CoA indicated that IC(50) values were neither dependent on mitochondrial subpopulation nor affected by exercise training. However, in IMF mitochondria, training reduced the Hill coefficient (P < 0.05), suggesting altered CPT1beta kinetics. These results demonstrate that endurance exercise provokes subpopulation-specific changes in mitochondrial function that are characterized by enhanced fatty acid oxidation and modified CPT1beta-malonyl-CoA dynamics.

Animals↗

PubMed2005

Peer instruction enhanced meaningful learning: ability to solve novel problems.

Students must be able to interpret, relate, and incorporate new information with existing knowledge and apply the new information to solve novel problems. Peer instruction is a cooperative learning technique that promotes critical thinking, problem solving, and decision-making skills. Therefore, we tested the hypothesis that peer instruction enhances meaningful learning or transfer, defined as the student's ability to solve novel problems or the ability to extend what has been learned in one context to new contexts. To test this hypothesis, our undergraduate exercise physiology class of 38 students was randomly divided into two groups: group A (n = 19) and group B (n = 19). A randomized crossover design in which students either answered questions individually or during peer instruction was used to control for time and order effects. The first factor that influences meaningful learning is the degree of mastery of the original material. Importantly, peer instruction significantly enhanced mastery of the original material. Furthermore, the student's ability to solve novel problems was significantly enhanced following peer instruction. Thus pausing two to three times during a 50-min class to allow peer instruction enhanced the mastery of the original material and enhanced meaningful learning, i.e., the student's ability to solve novel problems.

Aptitude↗

PubMed2003

Active involvement of PKC for insulin-mediated rates of muscle protein synthesis in Zucker rats.

A recent report from our group demonstrated that insulin facilitates muscle protein synthesis in obese Zucker rats. The purpose of this study was to determine whether PKC, a probable modulator of insulin signal transduction and/or mRNA translation, has a role in this insulin-mediated anabolic response. In the first portion of the study, gastrocnemius muscles of lean and obese Zucker rats (n = 5-7 for each phenotype) were bilaterally perfused with or without insulin to assess cytosolic and membrane PKC activity. Limbs perfused with insulin demonstrated greater PKC activity in both lean and obese Zucker rats (P < 0.05) compared with no insulin, but overall activity was greater in obese animals (by approximately 27% compared with lean, P < 0.05). To determine whether PKC plays a role in muscle protein synthesis, hindlimbs (n = 6-8 for each phenotype) were bilaterally perfused with or without insulin and/or GF-109203X (GF; a PKC inhibitor). The presence of GF did not influence the rates of insulin-mediated protein synthesis in gastrocnemius muscle of lean Zucker rats. However, when obese rats were perfused with GF (P < 0.05), the effect of insulin on elevating rates of protein synthesis was not observed. We also used phorbol 12-myristate 13-acetate (TPA, a PKC activator; n = 5-7 for each phenotype) with and without insulin to determine the effect of PKC activation on muscle protein synthesis. TPA alone did not elevate muscle protein synthesis in lean or obese rats. However, TPA plus insulin resulted in elevated rates of protein synthesis in both phenotypes that were similar to rates of insulin alone of obese rats. These results suggest that PKC is a modulator and is necessary, but not sufficient, for insulin-mediated protein anabolic responses in skeletal muscle.

Animals↗

PubMed2003

Acute endurance exercise increases skeletal muscle uncoupling protein-3 gene expression in untrained but not trained humans.

In rodents, acute exercise increases skeletal muscle uncoupling protein (UCP) gene expression and is associated with elevations in serum nonesterified fatty acids (NEFA). To test whether contractions increase UCP mRNA levels in humans, vastus lateralis biopsies were obtained 1 hour postexercise from untrained and trained subjects and analyzed for UCP-2 and UCP-3 long (UCP-3(L)) and short (UCP-3(S)) isoforms. The acute exercise bout (graded cycling protocol; 65% to 85% relative VO(2)max) induced significant (P <.01) elevations in serum NEFA in both untrained and trained subjects, but the increase in untrained subjects was significantly (P <.05) greater (60% v 30%). Ribonuclease protection assay demonstrated that basal levels of all UCP isoforms measured were similar between the 2 groups. However, acute exercise induced a significant increase (P <.02) in both UCP-3(L) and UCP-3(S), but not UCP-2 mRNA levels in untrained, but not trained subjects. Correlation analysis did not show a significant relationship between exercise-induced changes in NEFA and UCP-3 levels. These results demonstrate that acute endurance exercise increases UCP-3 gene expression only in untrained skeletal muscle, but this effect does not seem to be tightly linked to the exercise-induced fluctuations in serum NEFA levels.

Adult↗

PubMed2003

Student retention of course content is improved by collaborative-group testing.

We recently reported that collaborative testing (i.e., group test taking) increased student performance on quizzes. It is unknown, however, whether collaborative testing improves student retention of course content. Therefore, this study was designed to test the hypotheses that collaborative-group testing improves student retention of course content. To test this hypothesis, our undergraduate exercise physiology class of 38 students was randomly divided into two groups: group A (n = 19) and group B (n = 19). During exam 1, students from both groups answered questions in the traditional format as individuals. Immediately after completing the exam as individuals, students from group A answered a randomly selected subset of questions from exam 1 in groups of two (1 group had 3 students) to test the effectiveness of collaborative-group testing on test performance and level of student retention. On the next exam (exam 2, 4 wk later), students from both groups answered questions in the traditional format as individuals and responded to the same subset of questions from exam 1. The subset of questions was analyzed to determine the level of retention of the original test material. In addition, immediately after completing the exam as individuals, students from group B answered a randomly selected subset of questions from exam 2 in groups of two (1 group had 3 students). Finally, on the next exam (exam 3, 4 wk later), students from both groups answered questions in the traditional format as individuals and responded to the same subset of questions from exam 2. This protocol followed a randomized crossover design to control for time and order effects. Student retention of course content was reduced when students completed the original examinations individually. In sharp contrast, student retention was improved (P < 0.05) when students completed the original examinations in groups. Results suggest that collaborative testing is an effective strategy to enhance learning and increase student retention of course content.

Cooperative Behavior↗

PubMed2002

Skeletal muscle lipid metabolism with obesity.

The objectives of this study were to 1). examine skeletal muscle fatty acid oxidation in individuals with varying degrees of adiposity and 2). determine the relationship between skeletal muscle fatty acid oxidation and the accumulation of long-chain fatty acyl-CoAs. Muscle was obtained from normal-weight [n = 8; body mass index (BMI) 23.8 +/- 0.58 kg/m(2)], overweight/obese (n = 8; BMI 30.2 +/- 0.81 kg/m(2)), and extremely obese (n = 8; BMI 53.8 +/- 3.5 kg/m(2)) females undergoing abdominal surgery. Skeletal muscle fatty acid oxidation was assessed in intact muscle strips. Long-chain fatty acyl-CoA concentrations were measured in a separate portion of the same muscle tissue in which fatty acid oxidation was determined. Palmitate oxidation was 58 and 83% lower in skeletal muscle from extremely obese (44.9 +/- 5.2 nmol x g(-1) x h(-1)) patients compared with normal-weight (71.0 +/- 5.0 nmol x g(-1) x h(-1)) and overweight/obese (82.2 +/- 8.7 nmol x g(-1) x h(-1)) patients, respectively. Palmitate oxidation was negatively (R = -0.44, P = 0.003) associated with BMI. Long-chain fatty acyl-CoA content was higher in both the overweight/obese and extremely obese patients compared with normal-weight patients, despite significantly lower fatty acid oxidation only in the extremely obese. No associations were observed between long-chain fatty acyl-CoA content and palmitate oxidation. These data suggest that there is a defect in skeletal muscle fatty acid oxidation with extreme obesity but not overweight/obesity and that the accumulation of intramyocellular long-chain fatty acyl-CoAs is not solely a result of reduced fatty acid oxidation.

Acyl Coenzyme A↗

PubMed2002

Evidence of a malonyl-CoA-insensitive carnitine palmitoyltransferase I activity in red skeletal muscle.

Carnitine palmitoyltransferase I (CPT I), which is expressed as two distinct isoforms in liver (alpha) and muscle (beta), catalyzes the rate-limiting step in the transport of fatty acid into the mitochondria. Malonyl-CoA, a potent inhibitor of CPT I, is considered a key regulator of fatty acid oxidation in both tissues. Still unanswered is how muscle beta-oxidation proceeds despite malonyl-CoA concentrations that exceed the IC(50) for CPT Ibeta. We evaluated malonyl-CoA-suppressible [(14)C]palmitate oxidation and CPT I activity in homogenates of red (RG) and white (WG) gastrocnemius, soleus (SOL), and extensor digitorum longus (EDL) muscles. Adding 10 microM malonyl-CoA inhibited palmitate oxidation by 29, 39, 60, and 89% in RG, SOL, EDL, and WG, respectively. Thus malonyl-CoA resistance, which correlated strongly (0.678) with absolute oxidation rates (RG > SOL > EDL > WG), was greater in red than in white muscles. Similarly, malonyl-CoA-resistant palmitate oxidation and CPT I activity were greater in mitochondria from RG compared with WG. Ribonuclease protection assays were performed to evaluate whether our data might be explained by differential expression of CPT I splice variants. We detected the presence of two CPT Ibeta splice variants that were more abundant in red compared with white muscle, but the relative expression of the two mRNA species was unrelated to malonyl-CoA resistance. These results provide evidence of a malonyl-CoA-insensitive CPT I activity in red muscle, suggesting fiber type-specific expression of distinct CPT I isoforms and/or posttranslational modulations that have yet to be elucidated.

Alternative Splicing↗