Metabolic Inflexibility in Response to Lipid Oversupply with Obesity: Epigenetic Modifications Play a Role

The ability to adjust substrate oxidation according to nutrient availability has been termed `metabolic flexibility' and is a critical factor in overall metabolic health. In respect to fatty acid oxidation (FAO) metabolic flexibility appears to be compromised with severe obesity (BMI > 40kg/m2). When given a high-fat diet, healthy lean individuals increase their FAO, which is accompanied by increased expression of lipid-oxidizing genes. We observed an impairment in the ability to increase FAO in response to a high-fat diet in the skeletal muscle of obese individuals, which was accompanied by little or no change in the transcriptional upregulation of genes involved in FAO. These data indicate a differential response to lipid oversupply with obesity which could contribute to positive lipid balance and weight gain.   The molecular mechanisms contributing to this metabolic inflexibility with severe obesity are not evident. Acute epigenetic modifications of the genome, such as DNA methylation and histone acetylation, may provide a connection between nutritional factors, gene expression, and metabolic health. The purpose of the present study was therefore to determine if the expression of genes linked with FAO differed in a manner indicative of a lack of metabolic flexibility with obesity and to what extent the differential responses to lipid oversupply were linked with the chromatin environment and/or the methylation signature of these genes.   By utilizing human skeletal muscle cultures (HSkMC) we were able to study the molecular adaptations to a lipid stimulus in the skeletal muscle of lean and obese humans. The main findings were that: 1) the coordinated activation of genes linked with FAO among lean individuals in response to lipid oversupply is largely absent with obesity as evidenced by a blunted upregulation of several vital transcriptional regulators and 2) that changes in CpG methylation, increased histone acetylation, and transcription factor binding accompanied this response, suggesting that acute epigenetic modifications play a role in the lipid-induced upregulation of these genes. These data provide the novel information that with severe obesity the metabolic inflexibility evident in response to lipid exposure may be linked with an inability to upregulate transcriptional regulators caused by differential epigenetic modifications.  Ph.D

Students’ Perceptions of an Applied Research Experience in an Undergraduate Exercise Science Course

International Journal of Exercise Science 10(7): 926-941, 2017. Applied research experiences can provide numerous benefits to undergraduate students, however few studies have assessed the perceptions of Exercise Science (EXS) students to an applied research experience. The purpose of this study was two-fold: 1) to describe the rationale and implementation of an applied research experience into an EXS curriculum and 2) to evaluate EXS undergraduate students’ perceptions of an applied research experience. An EXS measurement course was chosen for implementation of an applied research experience. The applied research experience required groups of students to design, implement, and evaluate a student-led research project. Fourteen questions were constructed, tailored to EXS undergraduate students, to assess students’ perceptions of the experience. Qualitative analysis was used for all applicable data, with repeated trends noted; quantitative data were collapsed to determine frequencies. There was an overall positive student perception of the experience and 85.7% of students agreed an applied research experience should be continued. 84.7% of students perceived the experience as educationally enriching, while 92.8% reported the experience was academically challenging. This experience allowed students to develop comprehensive solutions to problems that arose throughout the semester; while facilitating communication, collaboration, and problem solving. Students believed research experiences were beneficial, but could be time consuming when paired with other responsibilities. Results suggest an applied research experience has the potential to help further the development of EXS undergraduate students. Understanding student perceptions of an applied research experience may prove useful to faculty interested in engaging students in the research process

Metabolic Flexibility and Weight Status May Contribute to Inter-Individual Changes in Breastmilk Lipid Content in Response to an Acute Bout of Exercise: Preliminary Findings from a Pilot Study

International Journal of Exercise Science 13(2): 1756-1769, 2020. The purposes of this pilot study were to describe changes in breastmilk lipid content in response to an acute bout of moderate intensity exercise and to explore maternal metabolic health factors, including metabolic flexibility, which may impact this change. A cross-sectional, observational, pilot study design was performed in 14 women between 4 and 6 months postpartum. Whole body fasting lipid oxidation was assessed, a standardized high-fat breakfast was consumed, and lipid oxidation was again measured 120-minutes post-meal. Metabolic flexibility was determined by comparing the change in lipid oxidation before and after the meal. Women completed 30-minutes of moderate intensity treadmill walking 150-minutes post-meal. Breastmilk was expressed and analyzed for lipid content before and after exercise. Overall, there was no significant difference between pre- and post-exercise breastmilk lipid content (pre-exercise 59.4±36.1 g/L vs. post-exercise 52.5±20.7 g/L, p=0.26). However, five (36%) women had an increase in breastmilk lipid content in response to the exercise bout, compared to nine (64%) that had a decrease in breastmilk lipid content suggesting inter-individual variability. The change in breastmilk lipid content from pre- to post-exercise was positively correlated to metabolic flexibility (r=0.595, p=0.03). Additionally, post-exercise lipid content was positively correlated with body mass index (BMI), body composition, and postpartum weight retention. Preliminary findings from this pilot study suggest that metabolic flexibility and maternal weight status may help explain the inter-individual changes in breastmilk lipid content in response to an acute bout of moderate intensity exercise

Elevated Lipid Oxidation Is Associated with Exceeding Gestational Weight Gain Recommendations and Increased Neonatal Anthropometrics: A Cross-Sectional Analysis

BACKGROUND: Deviations from gestational weight gain (GWG) recommendations are associated with unfavorable maternal and neonatal outcomes. There is a need to understand how maternal substrate metabolism, independent of weight status, may contribute to GWG and neonatal outcomes. The purpose of this study was to explore the potential link between maternal lipid oxidation rate, GWG, and neonatal anthropometric outcomes. METHODS: Women (N = 32) with a lean pre-pregnancy BMI were recruited during late pregnancy and substrate metabolism was assessed using indirect calorimetry, before and after consumption of a high-fat meal. GWG was categorized as follows: inadequate, adequate, or excess. Shortly after delivery (within 48 h), neonatal anthropometrics were obtained. RESULTS: Using ANOVA, we found that fasting maternal lipid oxidation rate (grams/minute) was higher (p = 0.003) among women with excess GWG (0.1019 ± 0.0416) compared to women without excess GWG (inadequate = 0.0586 ± 0.0273, adequate = 0.0569 ± 0.0238). Findings were similar when lipid oxidation was assessed post-meal and also when expressed relative to kilograms of fat free mass. Absolute GWG was positively correlated to absolute lipid oxidation expressed in grams/minute at baseline (r = 0.507, p = 0.003), 2 h post-meal (r = 0.531, p = 0.002), and 4 h post-meal (r = 0.546, p = 0.001). Fasting and post-meal lipid oxidation (grams/minute) were positively correlated to neonatal birthweight (fasting r = 0.426, p = 0.015; 2-hour r = 0.393, p = 0.026; 4-hour r = 0.540, p = 0.001) and also to neonatal absolute fat mass (fasting r = 0.493, p = 0.004; 2-hour r = 0.450, p = 0.010; 4-hour r = 0.552, p = 0.001). CONCLUSIONS: A better understanding of the metabolic profile of women during pregnancy may be critical in truly understanding a woman\u27s risk of GWG outside the recommendations. GWG counseling during prenatal care may need to be tailored to women based not just on their weight status, but other metabolic characteristics

Mitochondrial Respiratory Capacity and Content Are Normal in Young Insulin-Resistant Obese Humans

Considerable debate exists about whether alterations in mitochondrial respiratory capacity and/or content play a causal role in the development of insulin resistance during obesity. The current study was undertaken to determine whether such alterations are present during the initial stages of insulin resistance in humans. Young (∼23 years) insulin-sensitive lean and insulin-resistant obese men and women were studied. Insulin resistance was confirmed through an intravenous glucose tolerance test. Measures of mitochondrial respiratory capacity and content as well as H(2)O(2) emitting potential and the cellular redox environment were performed in permeabilized myofibers and primary myotubes prepared from vastus lateralis muscle biopsy specimens. No differences in mitochondrial respiratory function or content were observed between lean and obese subjects, despite elevations in H(2)O(2) emission rates and reductions in cellular glutathione. These findings were apparent in permeabilized myofibers as well as in primary myotubes. The results suggest that reductions in mitochondrial respiratory capacity and content are not required for the initial manifestation of peripheral insulin resistance

Modifiable Maternal Factors and Their Relationship to Postpartum Depression

The purpose of the study was to examine how modifiable maternal factors (body mass index (BMI), household income, fatigue, sleep, breastfeeding status, diet, and physical activity) relate to postpartum depression (PPD) at 6 and 12 months postpartum. Participants (n = 26) participated in two study visits (6 and 12 months postpartum) where vitals, weight, body composition (skinfold anthropometrics), and physical activity levels (Actigraph GTX9 accelerometer) were assessed. Validated instruments (BRUMS-32, Subjective Exercise Experience Scale, Pittsburg Sleep Quality index, NIH breastfeeding survey, NIH Dietary History Questionnaire, and Edinburg Postnatal Depression Scale) assessed lifestyle and demographic factors of interest. PPD at six months was correlated to PPD at 12 months (r = 0.926, p < 0.001). At six months postpartum, PPD was positively correlated to BMI (r = 0.473, p = 0.020) and fatigue (r = 0.701, p < 0.001), and negatively correlated to household income (r = −0.442, p = 0.035). Mothers who were breastfeeding had lower PPD scores (breastfeeding 3.9 ± 3.5 vs. not breastfeeding 7.6 ± 4.8, p = 0.048). At 12 months, PPD was positively correlated to sleep scores (where a higher score indicates poorer sleep quality) (r = 0.752, p < 0.001) and fatigue (r = 0.680, p = 0.004). When analyzed collectively via regression analyses, household income and fatigue appeared to be the strongest predictors of PPD at six months postpartum

Metabolic Inflexibility in Response to Lipid Oversupply with Obesity: Epigenetic Modifications Play a Role

The ability to adjust substrate oxidation according to nutrient availability has been termed `metabolic flexibility' and is a critical factor in overall metabolic health. In respect to fatty acid oxidation (FAO) metabolic flexibility appears to be compromised with severe obesity (BMI > 40kg/m2). When given a high-fat diet, healthy lean individuals increase their FAO, which is accompanied by increased expression of lipid-oxidizing genes. We observed an impairment in the ability to increase FAO in response to a high-fat diet in the skeletal muscle of obese individuals, which was accompanied by little or no change in the transcriptional upregulation of genes involved in FAO. These data indicate a differential response to lipid oversupply with obesity which could contribute to positive lipid balance and weight gain. The molecular mechanisms contributing to this metabolic inflexibility with severe obesity are not evident. Acute epigenetic modifications of the genome, such as DNA methylation and histone acetylation, may provide a connection between nutritional factors, gene expression, and metabolic health. The purpose of the present study was therefore to determine if the expression of genes linked with FAO differed in a manner indicative of a lack of metabolic flexibility with obesity and to what extent the differential responses to lipid oversupply were linked with the chromatin environment and/or the methylation signature of these genes. By utilizing human skeletal muscle cultures (HSkMC) we were able to study the molecular adaptations to a lipid stimulus in the skeletal muscle of lean and obese humans. The main findings were that: 1) the coordinated activation of genes linked with FAO among lean individuals in response to lipid oversupply is largely absent with obesity as evidenced by a blunted upregulation of several vital transcriptional regulators and 2) that changes in CpG methylation, increased histone acetylation, and transcription factor binding accompanied this response, suggesting that acute epigenetic modifications play a role in the lipid-induced upregulation of these genes. These data provide the novel information that with severe obesity the metabolic inflexibility evident in response to lipid exposure may be linked with an inability to upregulate transcriptional regulators caused by differential epigenetic modifications