Eight Weeks of Daily Cannabidiol Supplementation Improves Sleep Quality and Immune Cell Cytotoxicity.

BACKGROUND: The endocannabinoid system is active in nervous and immune cells and involves the expression of two cannabinoid receptor genes (CB1 and CB2), along with endogenous endocannabinoid ligands, 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (anandamide), and their synthetic enzymes. Cannabidiol (CBD) is a non-intoxicating exogenous cannabinoid agonist derived from plants that, at high doses, has received FDA approval as an anticonvulsant for epileptic seizures, and at low doses is marketed as a food-grade supplement for improved mental health, sleep quality, and immunological function. At present, the predominance of published CBD clinical research has focused on ameliorative or disease-specific intervention, with few trials investigating CBD effects in healthy populations. METHODS: This clinical study aimed to investigate the effects of 8 weeks of 50 mg oral CBD on mental health, sleep quantity and quality, and immune cell function in healthy, college-aged individuals. Twenty-eight participants (average age 25.9 ± 6.1 y) were randomized to receive either daily oral capsules of 50 mg of CBD (CB, n = 14) or a calorie-matched placebo (CN, n = 14). Participants completed pre- and post-intervention assessments, including anthropometric measurements, mental health surveys, sleep analysis, and immunological function assessments. RESULTS: After completing the 8-week intervention, there were no significant changes in body weight and BMI (CN: 1.09 ± 0.89%: CB: 1.41 ± 1.07%), or body fat percentage (CN: 9.01 ± 7.51%: CB: 8.57 ± 7.81%), respectively (values are % change pre to post, p > 0.05). There were also no significant differences between CB and CN groups with respect to mental health measures, sleep quantity, or circulating immunophenotype as a result of the intervention. However, the CB group experienced significant improvements in sleep quality measured objectively using a sleep questionnaire (p = 0.0023) and enhanced Natural Killer (NK) immune cell function assessed in situ (p = 0.0125). CONCLUSIONS: Eight weeks of daily 50 mg CBD may improve sleep quality, and NK immunosurveillance in healthy, younger adults.

Effects of Oral Cannabidiol on Health and Fitness in Healthy Adults: An 8-Week Randomized Trial.

BACKGROUND: There is a lack of research on the effects of cannabidiol (CBD) on health-related fitness, physical activity, cognitive health, psychological wellbeing, and concentrations of C-reactive protein (CRP) in healthy individuals. CBD has potential anti-inflammatory and neuroprotective effects. METHODS: This study aimed to investigate the effects of 8 weeks of CBD on the above-mentioned measures in healthy individuals. Forty-eight participants were randomized into two groups receiving either oral capsules of 50 mg of CBD or a calorie-matched placebo daily. Participants completed pre- and post-intervention assessments, including blood draws, body composition, fitness, physical activity, and self-reported surveys. RESULTS: There were no significant differences between groups regarding body composition, aerobic fitness, muscular strength, physical activity, cognitive health, psychological wellbeing, and resting CRP concentrations. However, the placebo group experienced a decline in mean peak power and relative peak power compared to the CBD group. CONCLUSIONS: The results suggest that 8 weeks of CBD supplementation may prevent declines in anaerobic fitness over time. However, long-term CBD supplementation may not be beneficial for altering measures of health-related fitness, mental health, and inflammation in healthy individuals.

Chronic cannabis use is associated with altered monocyte phenotype, immune response, and depression in physically active individuals.

Introduction: This study evaluated depression, monocyte phenotype, and immune function in physically active cannabis users. Methods: Participants (N = 23) were classified as either cannabis users (CU, n = 11) or non-users (NU, n = 12). White blood cells isolated from blood were analyzed for co-expression of cluster of differentiation 14 and 16 using flow cytometry. Lipopolysaccharide (LPS) was cultured with whole blood and assessed for interleukin-6 and tumor necrosis factor-α (TNF-α) release. Results: The percentage of white blood cells classified as monocytes was not different between groups; however, CU had a significantly greater percentage of monocytes classified as intermediate (p = 0.02). When standardized per milliliter of blood, CU had significantly greater numbers of total monocytes (p = 0.01), classical monocytes (p = 0.02), and intermediate monocytes (p = 0.01). Intermediate monocytes per milliliter of blood were positively correlated to the number of times CU used cannabis per day (r = 0.864, p < 0.01) and Beck Depression Inventory-II (BDI-II) score (r = 0.475, p = 0.03), which was significantly greater in CU (5.1 ± 4.8) compared with NU (0.8 ± 1.0; p < 0.01). CU released significantly less TNF-α per monocyte in response to LPS. Conclusions: CU had altered monocyte phenotypes and functions compared with NU. Elevations in intermediate monocytes were positively correlated with measures of cannabis use and BDI-II score.

Regular Use of Cannabis in Female Athletes Is Associated With a Reduction in Early Anaerobic Power Production.

ABSTRACT: Lisano, JK, Flores, VA, Kisiolek, JN, and Stewart, LK. Regular use of cannabis in female athletes is associated with a reduction in early anaerobic power production. J Strength Cond Res 37(3): 616-622, 2023-Despite a growing number of claims related to the ability of cannabis use to affect health and performance, there is limited research available, especially in female athletes. This cross-sectional study aimed to determine whether chronic cannabis use in physically active female athletes is related to altered health and performance. Healthy, physically active, female cannabis users (CU: n = 12) and noncannabis users (NU: n = 12) with an average age of 23.8 ± 3.7 years and 19.3 ± 4.2% body fat completed athletic performance and health assessments. Significance was set at alpha = 0.05. The age of onset of regular cannabis use was 20.1 ± 2.8 years in CU with an average duration of cannabis use of 5.8 ± 3.1 years. There were no differences between groups with respect to body size, body composition, pulmonary function, cardiorespiratory function, or muscular strength. Cannabis users produced significantly less power in the first 2 stages of the Wingate assessment, but CU experienced significantly less anaerobic fatigue. Although body composition and cardiovascular fitness were comparable, average C-reactive protein concentration classified CU with higher risk for cardiovascular disease (CVD). Athletes and coaches who rely heavily on anaerobic performance should consider these findings because they indicate that regular cannabis use may affect early power production and CVD risk.

Short Term, Oral Supplementation with Optimized Curcumin Does Not Impair Performance Improvements Associated with High Intensity Interval Training.

Curcumin may improve athletic performance through a reduction in inflammation following exercise and improve mental states of well-being. The purpose of this investigation was to explore the effects of a 14 day HIIT intervention and oral supplementation with Longvida® optimized curcumin on athletic performance, lactate response, and well-being. Sixteen males and twenty females participated in a double-blinded, randomized, placebo-controlled trial to explore the effects of Longvida(R) optimized curcumin (1.0 g/day) and or a placebo (PLA) taken daily during a 14 day HIIT protocol. Participants were randomized into two groups, then evaluated in three groups, curcumin-fast (CURF), curcumin-slow (CURS) and placebo. Curcumin-fast and curcumin-slow were separated by their 16.1 km cycling time trial performance (TT) with CURF and CURS determined by a TT <30 min and >30 min at the pre intervention time point, respectively. Cycling time-trial performance, blood lactate response, and well-being assessments were determined at pre and post 14 day HIIT intervention time points. Blood lactate was recorded at baseline, 8.01 km, 15.1 km, and 1 min post, and 4 min post of the pre and post intervention TT. Following the internvetion, CONP and CURS experienced with 8.15% and 5.04% improvements in TT performance times, while CURF experienced a 0.57% improvement in TT performance time. No changes were observed with respect to other measures. When curcumin is taken daily in conjunction with 14 days of HIIT on a cycle ergometer, cycling performance in either well trained or more recreationally trained athletes is not impaired. Although the improvements in TT performance were not stasticially significant, they are noteworthy.

Kefir Is a Viable Exercise Recovery Beverage for Cancer Survivors Enrolled in a Structured Exercise Program.

PURPOSE: This study investigated the effects of 12 wk of postexercise kefir consumption in cancer survivors who have undergone chemotherapy and/or radiation therapy. METHODS: All participants were enrolled in a structured exercise training program and separated into kefir (KEF) or control (CON) treatment groups. KEF consumed 8 oz. of kefir after exercise sessions (3 d·wk-1) for 12 wk. Outcome measures included assessments for body size and composition, aerobic fitness and muscular strength, medical history, and psychological state at pre- and postintervention time points. Blood was collected and analyzed for C-reactive protein (CRP), interleukin 6 (IL-6), and lipopolysaccharide (LPS) concentrations, and LPS-stimulated whole blood IL-6 and tumor necrosis factor α production were obtained using enzyme-linked immunosorbent assays at both time points. Monocyte numbers and phenotype were obtained using flow cytometry. RESULTS: Participants (N = 24; 9 males and 15 females) were an average of 61 ± 9.9 yr old. Kefir consumption was associated with 6.3% (P = 0.034) improvements in lean body mass, as well as 51.4% (P = 0.046), 39.3% (P = 0.017), and 64.7% (P = 0.021) improvements in measures of depression, fatigue, and gastric distress, respectively. KEF also experienced a significant 35.4% (P = 0.01) reduction in circulating LPS along with an 18.0% increase (P < 0.001) in classical monocytes % and a 22.3% decrease (P = 0.04) in nonclassical monocytes %. There were no significant changes in any other variables. CONCLUSION: Twelve weeks of kefir consumption improved lean body mass, depression, fatigue, gastric distress, and a biomarker of gut dysbiosis. Kefir improved overall and classical monocyte numbers. Kefir should be considered as a component of a postexercise dietary regimen for cancer survivors.

Structured Exercise in Cancer Survivors: Is it Enough for Neural, Mental Health and Well-being?

The purpose of this cross-sectional study was to explore physical activity, depression, fatigue, and quality of life (QOL), and their relationship to brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in cancer survivors enrolled in a structured exercise program. Participants were recruited into two groups: in-treatment (IT), currently receiving chemotherapy and/or radiotherapy, and out of treatment (OT), not undergoing therapy. Participants wore accelerometers for 7 days and completed cardiorespiratory fitness, muscular strength, and depression, fatigue, and QOL assessments. Circulating BDNF and NGF concentrations were obtained using enzyme-linked immunosorbent assays. Thirty-two participants (IT: n = 13, OT: n = 19) with an average age of 63 years and BMI of 27.5, spent 78% of their waking hours engaged in sedentary behavior outside of exercise training. Significant correlations were observed between light physical activity (LPA) outside of exercise training and QOL in IT (r = 0.626, p = 0.030), and fatigue in OT (r = 0.553, p = 0.021). Moderate to vigorous physical activity (MVPA) outside of exercise training significantly correlated with leg press strength (r = 0.700, p = 0.008) in IT, and cardiorespiratory fitness (r = 0.440, p = 0.013) when groups were combined. Concentrations of NGF did not differ between groups, and in IT, BDNF was positively related to LPA outside of training and was significantly lower (87 ± 28.5 pg/mL) than in OT (137 ± 54 pg/mL; p=0.010). While structured exercise programs should focus on improving cardiorespiratory fitness and muscular strength during exercise training, these programs should consider physical activity outside of training, if well-tolerated, to potentially further lower fatigue and improve QOL in cancer survivors.

Chronic cannabis use and circulating biomarkers of neural health, stress, and inflammation in physically active individuals.

Previous research has associated cannabis use with altered circulating neurotrophins and biomarkers of immune health, but these relationships have yet to be fully explored in physically active individuals. The specific aim of this study was to explore the relationships between biomarkers of neural health: nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), immune health: interleukin 6 (IL-6), C-reactive protein (CRP), and cortisol, as well as the presence of depression, in physically active cannabis users (CU) and nonusers (NU). Male and female participants (N = 30; CU, n = 15, NU, n = 15) provided intravenous blood samples and underwent assessment of body composition, maximal oxygen consumption, and depression (Beck Depression Inventory-II (BDI-II)). Samples were analyzed for concentrations of NGF, BDNF, IL-6, CRP, and cortisol using ELISAs. CU and NU were compared using an unpaired t test. Pearson's correlation and multiple linear regression were used to evaluate relationships among variables. There were no significant differences in body size or composition, maximal oxygen consumption, total BDI-II Score, concentrations of NGF, IL-6, CRP, or cortisol between groups. BDNF was significantly lower in CU compared with NU (p = 0.02), with a significant negative relationship between BDNF and CRP (p = 0.02). Mean concentrations of CRP placed CU at higher risk for cardiovascular disease compared with NU. Total BDI-II score negatively correlated with BDNF (p = 0.02) and positively correlated with CRP (p = 0.02). Novelty Plasma BDNF was significantly lower in physically active cannabis users compared with NU. CU were classified at moderate risk for cardiovascular disease based on average circulating CRP compared with low risk for NU.

Cardiorespiratory fitness, visceral fat, and body fat, but not dietary inflammatory index, are related to C-reactive protein in cancer survivors.

BACKGROUND: The control of chronic inflammation has emerged as a target for improving the health of cancer survivors (CS). AIM: To examine differences in fitness and dietary characteristics of CS when grouped by low vs. moderate to high serum C-reactive protein (CRP). METHODS: CS (N = 26, mean age = 68 ± 12 years) were evaluated for body mass index (BMI), body composition, cardiorespiratory fitness, dietary intake, dietary inflammatory index (DII), and serum CRP. Participants were assigned to one of two groups based on serum CRP concentrations: low CRP (≤1 mg/L) (LWC; n = 13) or moderate to high (CRP > 1 mg/L) (MHC; n = 13) and t-tests compared them. Data are presented as mean ± SD. RESULTS: LWC had higher VO2peak values (mL/kg/min) (p = 0.0003), and lower visceral fat area (cm2) (p = 0.02) and body fat mass (kg) (p = 0.04). Secondary analysis using Pearson's correlation coefficients, including all current study participant data, found significant negative relationships between CRP and total dietary fat intake (p = 0.02), saturated fat (p = 0.03), and polyunsaturated fat (p = 0.03). CONCLUSION: CS with moderate to high serum CRP concentrations had higher fat mass, visceral fat mass, and lower cardiorespiratory fitness. There was a significant negative relationship between dietary, fat, polyunsaturated and saturated fat, and CRP. However, these dietary fat related findings warrant further investigation. To summarize, improving cardiorespiratory fitness, maintaining lower body fat, may be helpful in altering chronic inflammation in CS.

Performance and Health-Related Characteristics of Physically Active Males Using Marijuana.

Lisano, JK, Smith, JD, Mathias, AB, Christensen, M, Smoak, P, Phillips, KT, Quinn, CJ, and Stewart, LK. Performance and health-related characteristics of physically active men using marijuana. J Strength Cond Res 33(6): 1659-1669, 2019-The influence of chronic marijuana use on the performance and health of physically active individuals has yet to be fully elucidated. The purpose of this study was to explore pulmonary function, aerobic and anaerobic fitness, strength, serum testosterone, cortisol, C-reactive protein (CRP), Δ-9-tetrahydrocannabinol (THC), 11-nor-9-carboxy-Δ-9-tetrahydrocannabinol (THC-COOH), and 11-hydroxy-Δ-9-tetrahydrocannabinol (THC-OH) concentrations in a physically active population either using or not using marijuana. Healthy, physically active males (N = 24) were compared based on their marijuana-use status: marijuana users (MU; n = 12) and nonusers (NU; n = 12). Statistical analysis (p = 0.05) revealed no difference between groups for age, body mass, body mass index, body fat, forced expiratory volume in 1 second percentage, VO2max, anaerobic power output, strength measures, testosterone, or cortisol concentrations. Although not statistically significant, MU showed a trend to fatigue to a greater percentage of absolute power output than NU from the beginning to the end of the Wingate Anaerobic Power Assessment (p = 0.08, effect size = 0.75). C-reactive protein in MU (1.76 ± 2.81 mg·L) and NU (0.86 ± 1.49 mg·L) was not significantly different (p = 0.60) but placed MU at moderate risk and NU at low risk for cardiovascular disease. Anaerobic fatigue was the only performance variable to show a trend for difference between groups. These results suggest that marijuana use in physically active males may not have significant effects on performance; however, it may be linked to elevated concentrations of CRP which place users at a higher risk for cardiovascular disease.

Dietary Quercetin Attenuates Adipose Tissue Expansion and Inflammation and Alters Adipocyte Morphology in a Tissue-Specific Manner.

Chronic inflammation in adipose tissue may contribute to depot-specific adipose tissue expansion, leading to obesity and insulin resistance. Dietary supplementation with quercetin or botanical extracts containing quercetin attenuates high fat diet (HFD)-induced obesity and insulin resistance and decreases inflammation. Here, we determined the effects of quercetin and red onion extract (ROE) containing quercetin on subcutaneous (inguinal, IWAT) vs. visceral (epididymal, EWAT) white adipose tissue morphology and inflammation in mice fed low fat, high fat, high fat plus 50 µg/day quercetin or high fat plus ROE containing 50 µg/day quercetin equivalents for 9 weeks. Quercetin and ROE similarly ameliorated HFD-induced increases in adipocyte size and decreases in adipocyte number in IWAT and EWAT. Furthermore, quercetin and ROE induced alterations in adipocyte morphology in IWAT. Quercetin and ROE similarly decreased HFD-induced IWAT inflammation. However, quercetin and red onion differentially affected HFD-induced EWAT inflammation, with quercetin decreasing and REO increasing inflammatory marker gene expression. Quercetin and REO also differentially regulated circulating adipokine levels. These results show that quercetin or botanical extracts containing quercetin induce white adipose tissue remodeling which may occur through inflammatory-related mechanisms.

Skeletal Muscle PGC1α -1 Nucleosome Position and -260 nt DNA Methylation Determine Exercise Response and Prevent Ectopic Lipid Accumulation in Men.

Endurance exercise has been shown to improve lipid oxidation and increase mitochondrial content in skeletal muscle, two features that have shown dependence on increased expression of the peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α). It is also hypothesized that exercise-related alterations in PGC1α expression occur through epigenetic regulation of nucleosome positioning in association with differential DNA methylation status within the PGC1α promoter. In this study, we show that when primary human myotubes from obese patients with type 2 diabetes are exposed to lipolytic stimulus (palmitate, forskolin, inomycin) in vitro, nucleosome occupancy surrounding the -260 nucleotide (nt) region, a known regulatory DNA methylation site, is reduced. This finding is reproduced in vivo in the vastus lateralis from 11 healthy males after a single, long endurance exercise bout in which participants expended 650 kcal. Additionally, we show a significant positive correlation between fold change of PGC1α messenger RNA expression and -1 nucleosome repositioning away from the -260 nt methylation site in skeletal muscle tissue following exercise. Finally, we found that when exercise participants are divided into high and low responders based on the -260 nt methylation status, the -1 nucleosome is repositioned away from the regulatory -260 nt methylation site in high responders, those exhibiting a significant decrease in -260 nt methylation, but not in low responders. Additionally, high but not low responders showed a significant decrease in intramyocellular lipid content after exercise. These findings suggest a potential target for epigenetic modification of the PGC1α promoter to stimulate the therapeutic effects of endurance exercise in skeletal muscle.

Emerging Relationships Between Vitamin D Status, Physical Activity Habits, and Immune Indices in College-Aged Females.

It has been determined that individuals who are regularly physically active have more favorable inflammatory profiles; less is known about how vitamin D levels can impact inflammation. This study explored the relationship between inflammatory indices in physically active (PA) and not physically active (NPA) individuals with 25-hydroxyvitamin D (25OHD) concentrations either above or below optimal concentrations. All female subjects (n = 63, age 19 - 35 years) were evaluated for body composition, maximal aerobic capacity (VO2peak), and anaerobic power (Wingate). Blood samples were analyzed for 25OHD and C-reactive protein (CRP), stimulated with lipopolysaccharide (LPS) and assessed for interleukin-6 (IL-6) production, and used for flow cytometric analysis. PA (n = 30) had higher 25OHD levels (45.2 ± 2.7 vs. 17.05 ± 1.4 ng / mL; p = 0.015), higher VO2peak (p < 0.0001), lower body weight (p = 0.039) and lower estimated percent body fat (p = 0.011) compared to NPA (n = 33). PA also had lower LPS-stimulated IL-6 production compared to NPA (p = 0.0163), although there were no differences between resting CRP concentrations. NPA with optimal 25OHD had fewer total monocytes, CD14+CD16-cells, CD14+CD16+ cells, and decreased TLR4 expression on CD14+CD16+ cells compared to NPA with suboptimal 25OHD (< 32 ng / mL). In summary, regular physical activity was associated with higher serum 25OHD, healthier measures of body composition, and reduced stimulated IL-6 production. However, optimal vitamin D status was not associated with anti-inflammatory benefits beyond those which are provided by regular physical activity.

Dietary quercetin supplementation in mice increases skeletal muscle PGC1α expression, improves mitochondrial function and attenuates insulin resistance in a time-specific manner.

AIMS/HYPOTHESIS: High fat diet (HFD)-induced insulin resistance (IR) is partially characterized by reduced skeletal muscle mitochondrial function and peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1α) expression. Our previous study showed that a high dose of the bioflavonoid quercetin exacerbated HFD-induced IR; yet, others have demonstrated that quercetin improves insulin sensitivity. The aim of this study was to investigate whether differing doses of quercetin act in a time-dependent manner to attenuate HFD-induced IR in association with improved skeletal muscle mitochondrial function and PGC1α expression. METHODS: C57BL/6J mice were fed HFD for 3 or 8 wks, with or without a low (50 ug/day; HF+50Q) or high (600 ug/day, HF+600Q) dose of quercetin. Whole body and metabolic phenotypes and insulin sensitivity were assessed. Skeletal muscle metabolomic analysis of acylcarnitines and PGC1α mRNA expression via qRT-PCR were measured. RESULTS: Quercetin at 50 ug/day for 8 wk attenuated HFD-induced increases in fat mass, body weight and IR and increased PGC1α expression, whereas 600 ug/day of quercetin exacerbated fat mass accumulation without altering body weight, IR or PGC1α. PGC1α expression correlated with acylcarnitine levels similarly in HF and HF+600Q; these correlations were not present in HF+50Q. At both time points, energy expenditure increased in HF+50Q and decreased in HF+600Q, independent of PGC1α and IR. CONCLUSIONS/INTERPRETATION: Chronic dietary quercetin supplementation at low but not higher dose ameliorates the development of diet-induced IR while increasing PGC1α expression in muscle, suggesting that skeletal muscle may be an important target for the insulin-sensitizing effects of a low dose of quercetin.

Vitamin D status, body composition, and fitness measures in college-aged students.

Low vitamin D, commonly assessed as serum 25-hydroxyvitamin D (25OHD), is associated with the development of many age-related chronic diseases. A positive relationship exists between elevated 25OHD and muscle synthesis, strength, power, and decreased body fat in elderly individuals. However, these findings have not been consistently reported in younger healthy populations. The purpose of this study was to investigate the relationship between 25OHD and measures of body size, composition, metabolism, and physical fitness in a young physically active population. Thirty-nine subjects (20 men, 19 women; aged 23 ± 0.7 years) reported 6 times for testing. Blood was collected to determine 25OHD. Primary outcomes included the following: body mass index (BMI) and percent body fat (dual x-ray absorptiometry); resting metabolic rate; maximal oxygen uptake (V[Combining Dot Above]O2max); power output (Wingate); and muscular strength (8 repetition maximum for bench press, upright row, and leg extension and flexion exercises). Our analysis included all participants, and subgroup analyses for individuals with suboptimal 25OHD concentration below 35 ng·mL ("low"; n = 20, 25.97 ± 1.97 ng·mL) or equal to and above 35 ng·mL ("high"; n = 19, 44.15 ± 2.17 ng·mL). Twenty subjects in this study had serum levels of 25OHD below 35 ng·mL. There was a significant positive relationship between V[Combining Dot Above]O2max and serum 25OHD and a negative relationship between BMI and serum 25OHD. These data suggest that vitamin D deficiency is prevalent even in a young physically active population in the southern United States and that there was a positive relationship between a measure of cardiovascular fitness and serum 25OHD, and a negative relationship between serum 25OHD and BMI.

PGC1α -1 Nucleosome Position and Splice Variant Expression and Cardiovascular Disease Risk in Overweight and Obese Individuals.

PGC1α, a transcriptional coactivator, interacts with PPARs and others to regulate skeletal muscle metabolism. PGC1α undergoes splicing to produce several mRNA variants, with the NTPGC1α variant having a similar biological function to the full length PGC1α (FLPGC1α). CVD is associated with obesity and T2D and a lower percentage of type 1 oxidative fibers and impaired mitochondrial function in skeletal muscle, characteristics determined by PGC1α expression. PGC1α expression is epigenetically regulated in skeletal muscle to determine mitochondrial adaptations, and epigenetic modifications may regulate mRNA splicing. We report in this paper that skeletal muscle PGC1α -1 nucleosome (-1N) position is associated with splice variant NTPGC1α but not FLPGC1α expression. Division of participants based on the -1N position revealed that those individuals with a -1N phased further upstream from the transcriptional start site (UP) expressed lower levels of NTPGC1α than those with the -1N more proximal to TSS (DN). UP showed an increase in body fat percentage and serum total and LDL cholesterol. These findings suggest that the -1N may be a potential epigenetic regulator of NTPGC1α splice variant expression, and -1N position and NTPGC1α variant expression in skeletal muscle are linked to CVD risk. This trial is registered with clinicaltrials.gov, identifier NCT00458133.

Morphological divergence and flow-induced phenotypic plasticity in a native fish from anthropogenically altered stream habitats.

Understanding population-level responses to human-induced changes to habitats can elucidate the evolutionary consequences of rapid habitat alteration. Reservoirs constructed on streams expose stream fishes to novel selective pressures in these habitats. Assessing the drivers of trait divergence facilitated by these habitats will help identify evolutionary and ecological consequences of reservoir habitats. We tested for morphological divergence in a stream fish that occupies both stream and reservoir habitats. To assess contributions of genetic-level differences and phenotypic plasticity induced by flow variation, we spawned and reared individuals from both habitats types in flow and no flow conditions. Body shape significantly and consistently diverged in reservoir habitats compared with streams; individuals from reservoirs were shallower bodied with smaller heads compared with individuals from streams. Significant population-level differences in morphology persisted in offspring but morphological variation compared with field-collected individuals was limited to the head region. Populations demonstrated dissimilar flow-induced phenotypic plasticity when reared under flow, but phenotypic plasticity in response to flow variation was an unlikely explanation for observed phenotypic divergence in the field. Our results, together with previous investigations, suggest the environmental conditions currently thought to drive morphological change in reservoirs (i.e., predation and flow regimes) may not be the sole drivers of phenotypic change.

Remodeling the integration of lipid metabolism between liver and adipose tissue by dietary methionine restriction in rats.

Dietary methionine restriction (MR) produces an integrated series of biochemical and physiological responses that improve biomarkers of metabolic health, limit fat accretion, and enhance insulin sensitivity. Using transcriptional profiling to guide tissue-specific evaluations of molecular responses to MR, we report that liver and adipose tissue are the primary targets of a transcriptional program that remodeled lipid metabolism in each tissue. The MR diet produced a coordinated downregulation of lipogenic genes in the liver, resulting in a corresponding reduction in the capacity of the liver to synthesize and export lipid. In contrast, the transcriptional response in white adipose tissue (WAT) involved a depot-specific induction of lipogenic and oxidative genes and a commensurate increase in capacity to synthesize and oxidize fatty acids. These responses were accompanied by a significant change in adipocyte morphology, with the MR diet reducing cell size and increasing mitochondrial density across all depots. The coordinated transcriptional remodeling of lipid metabolism between liver and WAT by dietary MR produced an overall reduction in circulating and tissue lipids and provides a potential mechanism for the increase in metabolic flexibility and enhanced insulin sensitivity produced by the diet.

Curvilinear dose-response relationship of carbohydrate (0-120 g·h(-1)) and performance.

BACKGROUND: There is a lack of consensus regarding the optimal range of carbohydrate (CHO) ingestion rates recommended for endurance athletes. PURPOSE: This study investigated the relationship between CHO dose and cycling time trial performance to identify an optimal range of CHO ingestion rates for endurance performance. METHODS: Fifty-one cyclists and triathletes (28 ± 7 yr, mean ± SD) across four research sites completed four trials. Each trial consisted of a 2-h constant load ride at 95% of the workload that elicited a 4-mmol·L(-1) blood lactate concentration immediately followed by a computer-simulated 20-km time trial, which subjects were asked to complete as quickly as possible. Twelve CHO electrolyte (18 mmol·L(-1) Na, 3 mmol·L(-1) K, and 11 mmol·L(-1) Cl) beverages (three at each site) were tested in a double-blind manner, providing subjects 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, and 120 g CHO (1:1:1 glucose-fructose-maltodextrin) per hour during the 2-h constant load ride at a fluid intake rate of 1 L·h(-1). All subjects also consumed a noncaloric placebo on one counterbalanced test occasion. Data were natural log transformed, subjected to a mixed-model analysis, and are reported as adjusted treatment means. RESULTS: We estimate incremental performance improvements of 1.0%, 2.0%, 3.0%, 4.0%, and 4.7% at 9, 19, 31, 48, and 78 g·h, respectively, with diminishing performance enhancement seen at CHO levels >78 g·h(-1). CONCLUSIONS: CHO beverage ingestion and endurance (∼160 min) performance appear to be related in a curvilinear dose-response manner, with the best performance occurring with a CHO (1:1:1 glucose-fructose-maltodextrin) ingestion rate of 78 g·h(-1).

Shared and unique morphological responses of stream fishes to anthropogenic habitat alteration.

Understanding population-level responses to novel selective pressures can elucidate evolutionary consequences of human-altered habitats. Stream impoundments (reservoirs) alter riverine ecosystems worldwide, exposing stream fishes to uncommon selective pressures. Assessing phenotypic trait divergence in reservoir habitats will be a first step in identifying the potential evolutionary and ecological consequences of stream impoundments. We tested for body shape divergence in four stream-adapted fishes found in both habitats within three separate basins. Shape variation among fishes was partitioned into shared (exhibited by all species) and unique (species-specific) responses to reservoir habitats. All fishes demonstrated consistent significant shared and unique morphological responses to reservoir habitats. Shared responses were linked to fin positioning, decreased body depths and larger caudal areas; traits likely related to locomotion. Unique responses were linked to head shape, suggesting species-specific responses to abiotic conditions or changes to their trophic ecology in reservoirs. Our results highlight how human-altered habitats can simultaneously drive similar and unique trait divergence in native populations.