Overexpression of Long-Chain Acyl-CoA Synthetase 5 Increases Fatty Acid Oxidation and Free Radical Formation While Attenuating Insulin Signaling in Primary Human Skeletal Myotubes.

In rodent skeletal muscle, acyl-coenzyme A (CoA) synthetase 5 (ACSL-5) is suggested to localize to the mitochondria but its precise function in human skeletal muscle is unknown. The purpose of these studies was to define the role of ACSL-5 in mitochondrial fatty acid metabolism and the potential effects on insulin action in human skeletal muscle cells (HSKMC). Primary myoblasts isolated from vastus lateralis (obese women (body mass index (BMI) = 34.7 ± 3.1 kg/m²)) were transfected with ACSL-5 plasmid DNA or green fluorescent protein (GFP) vector (control), differentiated into myotubes, and harvested (7 days). HSKMC were assayed for complete and incomplete fatty acid oxidation ([1-14C] palmitate) or permeabilized to determine mitochondrial respiratory capacity (basal (non-ADP stimulated state 4), maximal uncoupled (carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP)-linked) respiration, and free radical (superoxide) emitting potential). Protein levels of ACSL-5 were 2-fold higher in ACSL-5 overexpressed HSKMC. Both complete and incomplete fatty acid oxidation increased by 2-fold (p < 0.05). In permeabilized HSKMC, ACSL-5 overexpression significantly increased basal and maximal uncoupled respiration (p < 0.05). Unexpectedly, however, elevated ACSL-5 expression increased mitochondrial superoxide production (+30%), which was associated with a significant reduction (p < 0.05) in insulin-stimulated p-Akt and p-AS160 protein levels. We concluded that ACSL-5 in human skeletal muscle functions to increase mitochondrial fatty acid oxidation, but contrary to conventional wisdom, is associated with increased free radical production and reduced insulin signaling.

Intellectual development is positively related to intrinsic motivation and course grades for female but not male students.

We hypothesized that the intellectual development of students, i.e., their beliefs about the nature of knowledge and learning, affects their intrinsic motivation and class performance. Specifically, we hypothesized that students with low intellectual development (i.e., the naive beliefs that knowledge is simple, absolute, and certain) have low intrinsic motivation and low class performance, whereas students with high intellectual development (i.e., more sophisticated beliefs that knowledge is complex, tentative, and evolving) have high intrinsic motivation and class performance. To test this hypothesis, we administered the Learning Context Questionnaire to measure intellectual development. In addition, we administered the Intrinsic Motivation Inventory to assess our students' intrinsic motivation. Furthermore, we performed regression analyses between intellectual development with both intrinsic motivation and class performance. The results document a positive relationship among intellectual development, intrinsic motivation, and class performance for female students only. In sharp contrast, there was a negative relationship between intellectual development, intrinsic motivation, and class performance for male students. The slope comparisons documented significant differences in the slopes relating intellectual development, intrinsic motivation, and class performance between female and male students. Thus, female students with more sophisticated beliefs that knowledge is personally constructed, complex, and evolving had higher intrinsic motivation and class performance. In contrast, male students with the naive beliefs that the structure of knowledge is simple, absolute, and certain had higher levels of intrinsic motivation and class performance. The results suggest that sex influences intellectual development, which has an effect on intrinsic motivation for learning a specific topic.

Higher levels of intrinsic motivation are related to higher levels of class performance for male but not female students.

Our students are naturally curious, with powerful intrinsic motives to understand their world. Accordingly, we, as teachers, must capitalize on this inherently active and curious nature so that learning becomes a lifelong activity where students take initiative for learning, are skilled in learning, and want to learn new things. Achieving this goal requires an understanding of student attitudes, beliefs, characteristics, and motivations. To achieve this goal, we administered the intrinsic motivation inventory (IMI) to assess our students' interest and enjoyment, perceived choice, and perceived competence while taking our undergraduate exercise physiology class (46 students; 20 female students and 26 male students). The interest and enjoyment subscale is considered the self-reported measure of intrinsic motivation. The perceived choice and perceived competence concepts are theorized to be positive predictors of both self-reported and behavioral measures of intrinsic motivation. Our results documented a significant increase in course grade with an increase in survey score for the interest and enjoyment subscale of the IMI when female and male students were combined. Specifically, each increase in survey score for the interest and enjoyment subscale of the IMI was associated with a significant (P < 0.05) increase of 3.9% in course grade. However, the increase in survey score was associated with a significantly greater (P < 0.05) increase in course grade for male (6.1%) compared with female (0.3%) students. These results have implications for both classroom practice and educational reform policies.

Does sex (female versus male) influence the impact of class attendance on examination performance?

The "conventional wisdom" is that grades are related to class attendance, i.e., students who attend classes more frequently obtain better grades and class attendance dramatically contributes to enhanced learning. However, the influence of sex (female vs. male) on this relationship is understudied. Furthermore, there have been several studies examining the impact of attendance on course grades that challenge the conventional wisdom. To address these issues, we determined the effect of class attendance on examination scores for female and male students enrolled in our undergraduate exercise physiology class of 51 students (20 female students and 31 male students). The experiment was designed not to interfere with the normal conduct of the course. Attendance was recorded in each class, and, although regular attendance was encouraged, it was not required and did not factor into the final grades. The final grade reflected the average days of attendance for female students only. Specifically, female students earning a grade above the class average attended 89 ± 4% of the classes; however, female students earning a grade below the class average attended only 64 ± 6% of the classes. In sharp contrast, there was no difference in the number of classes attended for male students earning grades above or below the class average (84 ± 3% vs. 79 ± 5%). Accordingly, some male students were absent frequently but scored above the class average, whereas other male students attended many classes but scored below the class average. Thus, the influence of regular attendance on examination performance is more important for female students than male students.

Progesterone increases skeletal muscle mitochondrial H2O2 emission in nonmenopausal women.

The luteal phase of the female menstrual cycle is associated with both 1) elevated serum progesterone (P4) and estradiol (E2), and 2) reduced insulin sensitivity. Recently, we demonstrated a link between skeletal muscle mitochondrial H(2)O(2) emission (mE(H2O2)) and insulin resistance. To determine whether serum levels of P4 and/or E(2) are related to mitochondrial function, mE(H2O2) and respiratory O(2) flux (Jo(2)) were measured in permeabilized myofibers from insulin-sensitive (IS, n = 24) and -resistant (IR, n = 8) nonmenopausal women (IR = HOMA-IR > 3.6). Succinate-supported mE(H2O2) was more than 50% greater in the IR vs. IS women (P < 0.05). Interestingly, serum P4 correlated positively with succinate-supported mE(H2O2) (r = 0. 53, P < 0.01). To determine whether P4 or E2 directly affect mitochondrial function, saponin-permeabilized vastus lateralis myofibers biopsied from five nonmenopausal women in the early follicular phase were incubated in P4 (60 nM), E2 (1.4 nM), or both. P4 alone inhibited state 3 Jo(2), supported by multisubstrate combination (P < 0.01). However, E2 alone or in combination with P4 had no effect on Jo(2). In contrast, during state 4 respiration, supported by succinate and glycerophosphate, mE(H2O2) was increased with P4 alone or in combination with E2 (P < 0.01). The results suggest that 1) P4 increases mE(H2O2) with or without E2; 2) P4 alone inhibits Jo(2) but not when E2 is present; and 3) P4 is related to the mE(H2O2) previously linked to skeletal muscle insulin resistance.