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We examined the effects of whey versus collagen protein on skeletal muscle cell signaling responses associated with mitochondrial biogenesis and protein synthesis in recovery from an acute training session completed with low carbohydrate availability. In a repeated-measures design (after adhering to a 36-hr exercise–dietary intervention to standardize preexercise muscle glycogen), eight males completed a 75-min nonexhaustive cycling protocol and consumed 22 g of a hydrolyzed collagen blend (COLLAGEN) or whey (WHEY) protein 45 min prior to exercise, 22 g during exercise, and 22 g immediately postexercise. Exercise decreased (p <.05) muscle glycogen content by comparable levels from pre- to postexercise in both trials (≈300–150 mmol/kg·dry weight). WHEY protein induced greater increases in plasma branched chain amino acids (p =.03) and leucine (p =.02) than COLLAGEN. Exercise induced (p <.05) similar increases in PGC-1α (fivefold) mRNA at 1.5 hr postexercise between conditions, although no effect of exercise (p >.05) was observed for p53, Parkin, and Beclin1 mRNA. Exercise suppressed (p <.05) p70S6K1 activity in both conditions immediately postexercise (≈25 fmol·min−1·mg−1). Postexercise feeding increased p70S6K1 activity at 1.5 hr postexercise (p <.05), the magnitude of which was greater (p <.05) in WHEY (180 ± 105 fmol·min−1·mg−1) versus COLLAGEN (73 ± 42 fmol·min−1·mg−1). We conclude that protein composition does not modulate markers of mitochondrial biogenesis when in recovery from a training session deliberately completed with low carbohydrate availability. By contrast, whey protein augments postexercise p70S6K activity compared with hydrolyzed collagen, as likely mediated via increased leucine availability. [ABSTRACT FROM AUTHOR]

Using guidance from the reach, efficacy, adoption, implementation, and maintenance evaluation framework, we aimed to qualitatively evaluate the participant experiences of a workplace high-intensity interval training (HIIT) intervention. Twelve previously insufficiently active individuals (four males and eight females) were interviewed once as part of three focus groups. Perceptions of program satisfaction, barriers to and facilitators of adherence, and persistence to exercise were explored. HIIT initiates interest because of its novelty, provides a sense of accomplishment, and overcomes the barriers of perceived lack of time. The feeling of relatedness between the participants can attenuate negative unpleasant responses during the HIIT sessions. HIIT, in this workplace setting, is an acceptable intervention for physically inactive adults. However, participants were reluctant to maintain the same mode of exercise, believing that HIIT sessions were for the very fit. [ABSTRACT FROM AUTHOR]

We investigated whether 20 candidate single nucleotide polymorphisms (SNPs) were associated with in vivo exercise‐induced muscle damage (EIMD), and with an in vitro skeletal muscle stem cell wound healing assay. Sixty‐five young, untrained Caucasian adults performed 120 maximal eccentric knee‐extensions on an isokinetic dynamometer to induce EIMD. Maximal voluntary isometric/isokinetic knee‐extensor torque, knee joint range of motion (ROM), muscle soreness, serum creatine kinase activity and interleukin‐6 concentration were assessed before, directly after and 48 h after EIMD. Muscle stem cells were cultured from vastus lateralis biopsies from a separate cohort (n = 12), and markers of repair were measured in vitro. Participants were genotyped for all 20 SNPs using real‐time PCR. Seven SNPs were associated with the response to EIMD, and these were used to calculate a total genotype score, which enabled participants to be segregated into three polygenic groups: 'preferential' (more 'protective' alleles), 'moderate', and 'non‐preferential'. The non‐preferential group was consistently weaker than the preferential group (1.93 ± 0.81 vs. 2.73 ± 0.59 N ∙ m/kg; P = 9.51 × 10−4) and demonstrated more muscle soreness (p = 0.011) and a larger decrease in knee joint ROM (p = 0.006) following EIMD. Two TTN‐AS1 SNPs in linkage disequilibrium were associated with in vivo EIMD (rs3731749, p ≤ 0.005) and accelerated muscle stem cell migration into the artificial wound in vitro (rs1001238, p ≤ 0.006). Thus, we have identified a polygenic profile, linked with both muscle weakness and poorer recovery following EIMD. Moreover, we provide evidence for a novel TTN gene‐cell‐skeletal muscle mechanism that may help explain some of the interindividual variability in the response to EIMD. [ABSTRACT FROM AUTHOR]

Exercise referral schemes (ERS) are used to promote physical activity within primary care. Traditionally, ERS are conducted in a gym or leisure-center setting, with exercise prescriptions based on moderate-intensity continuous training (MICT). Home-based high-intensity interval training (Home-HIIT) has the potential to reduce perceived barriers to exercise, including lack of time and access to facilities, compared to traditional MICT prescription used with ERS and improve health related outcomes. We hypothesized that Home-HIIT would mediate greater improvement in cardiorespiratory fitness (CRF) by virtue of greater adherence and compliance to the exercise prescription, compared to MICT. Methods: Patients enrolled on an ERS (Liverpool, United Kingdom) were recruited for a pragmatic trial. Participants self-selected either 12 weeks of MICT (45–135 min/week at 50–70% HRmax) or Home-HIIT (4–9 min × 1 min intervals at ≥80% of HRmax, interspersed with 1 min rest). The primary outcome was the change in CRF (VO2peak) at post-intervention (12 weeks) and follow-up (3-month post intervention), using intention-to-treat analysis. Results: 154 participants (age 48 ± 10y; BMI 30.5 ± 6.1 kg/m2) were recruited between October 2017 and March 2019, 87 (56%) participants chose Home-HIIT and 67 (44%) MICT. VO2peak increased post-intervention in both groups (MICT 3.9 ± 6.0 ml.kg–1.min–1, Home-HIIT 2.8 ± 4.5 ml.kg–1.min–1, P < 0.001), and was maintained at follow-up (P < 0.001). Fat mass was only reduced post MICT (MICT −1.5 ± 6.3 kg, P < 0.05, Home-HIIT −0.2 ± 2.0 kg, P = 1.00), but the reduction was not maintained at follow-up (MICT −0.6 ± 5.1 kg, Home-HIIT 0.0 ± 2.2 kg, P > 0.05). Adherence to the prescribed programs was similar (MICT 48 ± 35%, Home-HIIT 39 ± 36%, P = 0.77). Conclusion: This is the first study to evaluate the use of Home-HIIT for individuals in a primary care setting. Contrary to our hypothesis, adherence to both exercise prescriptions was poor, and CRF improved to a similar extent in both groups with improvements maintained at 3-month follow-up. We provide evidence that, although not superior, Home-HIIT could be an effective and popular additional exercise choice for patients within primary care based ERS. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT04553614]. [ABSTRACT FROM AUTHOR]

Objective: High intensity interval training (HIIT) is a time-efficient exercise modality to improve cardiorespiratory fitness, and has recently been popularised by social media influencers. However, little is known regarding acute physiological and perceptual responses to these online protocols compared to HIIT protocols used within research. The aim was to investigate acute physiological, perceptual and motivational responses to two HIIT protocols popular on social media, and compare these to two evidence-based protocols. Methods: Twenty-seven recreationally active (>1 exercise session /week) participants (Age: 22±3y, BMI: 24.3±2.4) completed a randomised cross-over study, whereby each participant completed four HIIT protocols, two already established in research (Ergo-60:60 (cycling 10x60s at 100%Wmaxwith 60s rest), BW-60:60 (body-weight exercises 10x60swith 60s rest)) and two promoted on social media (SM-20:10 (body-weight exercises 20x20swith 10s rest) and SM-40:20 (body-weight exercises 15x40s with 20s rest)). Blood lactate, heart rate (HR), feeling scale (FS), felt arousal scale (FSA), enjoyment and perceived competence were measured in response to each protocol. Results: Significant differences were observed between BW-60:60 and SM-20:10 for the proportion of intervals meeting the ACSM high-intensity exercise criterion (>80% of HRmax) (BW-60:60 93±10%, SM-20:10 74±20%, P = 0.039) and change in lactate (BW-60:60 +7.8±3.7mmol/L, SM-20:10 +5.5±2.6mmol/L, P = 0.001). The percentage of time spent above the criterion HR was also significantly lower in SM-20:10 compared to all other protocols (Ergo-60:60 13.9±4.9min, BW-60:60 13.5±3.5min, SM-40:20 12.1±2.4min, SM-20:10 7.7±3.1, P<0.05). No differences were observed in lowest reported FS between protocols (P = 0.268), but FS decreased linearly throughout Ergo-60:60 and BW-60:60 (first vs. last interval P<0.05), but not in SM-20:10 or SM-40:20 (P>0.05). Enjoyment was higher upon completion of BW-60:60 compared to Ergo-60:60 and SM-40:20 (P<0.05). Conclusions: This study shows that HIIT protocols available on social media offer an interesting real-world alternative for promoting exercise participation. Future studies should continue to investigate these highly popular and practical HIIT protocols. [ABSTRACT FROM AUTHOR]

Key points: Muscle glycogen and intramuscular triglycerides (IMTG, stored in lipid droplets) are important energy substrates during prolonged exercise.Exercise‐induced changes in lipid droplet (LD) morphology (i.e. LD size and number) have not yet been studied under nutritional conditions typically adopted by elite endurance athletes, that is, after carbohydrate (CHO) loading and CHO feeding during exercise.We report for the first time that exercise reduces IMTG content in both central and peripheral regions of type I and IIa fibres, reflective of decreased LD number in both fibre types whereas reductions in LD size were exclusive to type I fibres.Additionally, CHO feeding does not alter subcellular IMTG utilisation, LD morphology or muscle glycogen utilisation in type I or IIa/II fibres.In the absence of alterations to muscle fuel selection, CHO feeding does not attenuate cell signalling pathways with regulatory roles in mitochondrial biogenesis. We examined the effects of carbohydrate (CHO) feeding on lipid droplet (LD) morphology, muscle glycogen utilisation and exercise‐induced skeletal muscle cell signalling. After a 36 h CHO loading protocol and pre‐exercise meal (12 and 2 g kg–1, respectively), eight trained males ingested 0, 45 or 90 g CHO h–1 during 180 min cycling at lactate threshold followed by an exercise capacity test (150% lactate threshold). Muscle biopsies were obtained pre‐ and post‐completion of submaximal exercise. Exercise decreased (P < 0.01) glycogen concentration to comparable levels (∼700 to 250 mmol kg–1 DW), though utilisation was greater in type I (∼40%) versus type II fibres (∼10%) (P < 0.01). LD content decreased in type I (∼50%) and type IIa fibres (∼30%) (P < 0.01), with greater utilisation in type I fibres (P < 0.01). CHO feeding did not affect glycogen or IMTG utilisation in type I or II fibres (all P > 0.05). Exercise decreased LD number within central and peripheral regions of both type I and IIa fibres, though reduced LD size was exclusive to type I fibres. Exercise induced (all P < 0.05) comparable AMPKThr172 (∼4‐fold), p53Ser15 (∼2‐fold) and CaMKIIThr268 phosphorylation (∼2‐fold) with no effects of CHO feeding (all P > 0.05). CHO increased exercise capacity where 90 g h–1 (233 ± 133 s) > 45 g h–1 (156 ± 66 s; P = 0.06) > 0 g h–1 (108 ± 54 s; P = 0.03). In conditions of high pre‐exercise CHO availability, we conclude CHO feeding does not influence exercise‐induced changes in LD morphology, glycogen utilisation or cell signalling pathways with regulatory roles in mitochondrial biogenesis. Key points: Muscle glycogen and intramuscular triglycerides (IMTG, stored in lipid droplets) are important energy substrates during prolonged exercise.Exercise‐induced changes in lipid droplet (LD) morphology (i.e. LD size and number) have not yet been studied under nutritional conditions typically adopted by elite endurance athletes, that is, after carbohydrate (CHO) loading and CHO feeding during exercise.We report for the first time that exercise reduces IMTG content in both central and peripheral regions of type I and IIa fibres, reflective of decreased LD number in both fibre types whereas reductions in LD size were exclusive to type I fibres.Additionally, CHO feeding does not alter subcellular IMTG utilisation, LD morphology or muscle glycogen utilisation in type I or IIa/II fibres.In the absence of alterations to muscle fuel selection, CHO feeding does not attenuate cell signalling pathways with regulatory roles in mitochondrial biogenesis. [ABSTRACT FROM AUTHOR]

The methylome and transcriptome signatures following exercise that are physiologically and metabolically relevant to sporting contexts such as team sports or health prescription scenarios (e.g., high intensity interval training/HIIT) has not been investigated. To explore this, we performed two different sport/exercise relevant high-intensity running protocols in five male sport team members using a repeated measures design of: (1) change of direction (COD) versus; (2) straight line (ST) running exercise with a wash-out period of at least 2 weeks between trials. Skeletal muscle biopsies collected from the vastus lateralis 30 min and 24 h post exercise, were assayed using 850K methylation arrays and a comparative analysis with recent (subject-unmatched) sprint and acute aerobic exercise meta-analysis transcriptomes was performed. Despite COD and ST exercise being matched for classically defined intensity measures (speed × distance and number of accelerations/decelerations), COD exercise elicited greater movement (GPS-Playerload), physiological (HR), metabolic (lactate) as well as central and peripheral (differential RPE) exertion measures compared with ST exercise, suggesting COD exercise evoked a higher exercise intensity. The exercise response alone across both conditions evoked extensive alterations in the methylome 30 min and 24 h post exercise, particularly in MAPK, AMPK and axon guidance pathways. COD evoked a considerably greater hypomethylated signature across the genome compared with ST exercise, particularly at 30 min post exercise, enriched in: Protein binding, MAPK, AMPK, insulin, and axon guidance pathways. Comparative methylome analysis with sprint running transcriptomes identified considerable overlap, with 49% of genes that were altered at the expression level also differentially methylated after COD exercise. After differential methylated region analysis, we observed that VEGFA and its downstream nuclear transcription factor, NR4A1 had enriched hypomethylation within their promoter regions. VEGFA and NR4A1 were also significantly upregulated in the sprint transcriptome and meta-analysis of exercise transcriptomes. We also confirmed increased gene expression of VEGFA , and considerably larger increases in the expression of canonical metabolic genes PPARGC1A (that encodes PGC1- α) and NR4A3 in COD vs. ST exercise. Overall, we demonstrate that increased physiological/metabolic load via COD exercise in human skeletal muscle evokes considerable epigenetic modifications that are associated with changes in expression of genes responsible for adaptation to exercise. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?What is the absolute level of pre‐exercise glycogen concentration required to augment the exercise‐induced signalling response regulating mitochondrial biogenesis?What is the main finding and its importance?Commencing high‐intensity endurance exercise with reduced pre‐exercise muscle glycogen concentrations confers no additional benefit to the early signalling responses that regulate mitochondrial biogenesis. We examined the effects of graded muscle glycogen on the subcellular location and protein content of AMP‐activated protein kinase (AMPK) and peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) and mRNA expression of genes associated with the regulation of mitochondrial biogenesis and substrate utilisation in human skeletal muscle. In a repeated measures design, eight trained male cyclists completed acute high‐intensity interval (HIT) cycling (8 × 5 min at 80% peak power output) with graded concentrations of pre‐exercise muscle glycogen. Following initial glycogen‐depleting exercise, subjects ingested 2 g kg−1 (L‐CHO), 6 g kg−1 (M‐CHO) or 14 g kg−1 (H‐CHO) of carbohydrate during a 36 h period, such that exercise was commenced with graded (P < 0.05) muscle glycogen concentrations (mmol (kg dw)−1: H‐CHO, 531 ± 83; M‐CHO, 332 ± 88; L‐CHO, 208 ± 79). Exercise depleted muscle glycogen to <300 mmol (kg dw)−1 in all trials (mmol (kg dw)−1: H‐CHO, 270 ± 88; M‐CHO, 173 ± 74; L‐CHO, 100 ± 42) and induced comparable increases in nuclear AMPK protein content (∼2‐fold) and PGC‐1α (∼5‐fold), p53 (∼1.5‐fold) and carnitine palmitoyltransferase 1 (∼2‐fold) mRNA between trials (all P < 0.05). The magnitude of increase in PGC‐1α mRNA was also positively correlated with post‐exercise glycogen concentration (P < 0.05). In contrast, neither exercise nor carbohydrate availability affected the subcellular location of PGC‐1α protein or PPAR, SCO2, SIRT1, DRP1, MFN2 or CD36 mRNA. Using a sleep‐low, train‐low model with a high‐intensity endurance exercise stimulus, we conclude that pre‐exercise muscle glycogen does not modulate skeletal muscle cell signalling. [ABSTRACT FROM AUTHOR]

New Findings: What is the topic of this review?This symposium review provides an overview of the recent work investigating whether a virtually monitored home‐based high‐intensity interval training (Home‐HIT) intervention reduces the fear of hypoglycaemia and other common barriers to exercise in people with type 1 diabetes.What advances does it highlight?Home‐HIT seems to offer a strategy to reduce fear of hypoglycaemia, while simultaneously removing other known barriers that prevent people with type 1 diabetes from taking up exercise, because it is time efficient, requires no travel time or costs associated with gym memberships, and allows people to exercise in their chosen environment. People with type 1 diabetes (T1D) are recommended to engage in regular exercise for a variety of health and fitness reasons. However, many lead a sedentary lifestyle and fail to meet the physical activity guidelines, in part because of the challenge of managing blood glucose concentration and fear of hypoglycaemia. A number of strategies designed to help people with T1D to manage their blood glucose during and after exercise have been investigated. Although many of these strategies show promise in facilitating blood glucose management during and after exercise, they do not target the many other common barriers to exercise that people with T1D face, such as difficulty with cost and travel time to gyms, limited access to exercise bikes and treadmills, and a possible dislike of exercising in front of others in public places. In this symposium review, we provide an overview of ongoing research into a virtually monitored home‐based high‐intensity interval training (Home‐HIT) programme that is designed to reduce these other common barriers to exercise. The conclusion of this review is that Home‐HIT seems to offer a strategy to reduce fear of hypoglycaemia, while simultaneously removing other known barriers preventing people with T1D from taking up exercise, such as being time efficient, requiring no travel time or costs associated with gym memberships, and giving them the opportunity to exercise in their chosen environment, reducing the embarrassment experienced by some when exercising in public. [ABSTRACT FROM AUTHOR]

Intramuscular triglycerides (IMTG) are a key substrate during prolonged exercise, but little is known about the rate of IMTG resynthesis in the postexercise period. We investigated the hypothesis that the distribution of the lipid droplet (LD)-associated perilipin (PLIN) proteins is linked to IMTG storage following exercise. Fourteen elite male triathletes (27 ± 1 yr, 66.5 ± 1.3 mL·kg−1·min−1) completed 4 h of moderate-intensity cycling. During the first 4 h of recovery, subjects received either carbohydrate or H2O, after which both groups received carbohydrate. Muscle biopsies collected pre- and postexercise and 4 and 24 h postexercise were analyzed using confocal immunofluorescence microscopy for fiber type-specific IMTG content and PLIN distribution with LDs. Exercise reduced IMTG content in type I fibers (−53%, P = 0.002), with no change in type IIa fibers. During the first 4 h of recovery, IMTG content increased in type I fibers (P = 0.014), but was not increased more after 24 h, where it was similar to baseline levels in both conditions. During recovery the number of LDs labeled with PLIN2 (70%), PLIN3 (63%), and PLIN5 (62%; all P < 0.05) all increased in type I fibers. Importantly, the increase in LDs labeled with PLIN proteins only occurred at 24 h postexercise. In conclusion, IMTG resynthesis occurs rapidly in type I fibers following prolonged exercise in highly trained individuals. Furthermore, increases in IMTG content following exercise preceded an increase in the number of LDs labeled with PLIN proteins. These data, therefore, suggest that the PLIN proteins do not play a key role in postexercise IMTG resynthesis. [ABSTRACT FROM AUTHOR]

Objective: Adopt a multidisciplinary approach to evaluate a virtually supervised home-based high-intensity interval training (Home-HIT) intervention in people with type 1 diabetes.Research Design and Methods: Eleven individuals with type 1 diabetes (seven women; age 30 ± 3 years; [Formula: see text] 2.5 ± 0.2 L/min; duration of diabetes 10 ± 2 years) completed 6 weeks of Home-HIT. A heart rate monitor and mobile phone application were used to provide feedback to the participants and research team on exercise intensity (compliance) and adherence.Results: Training adherence was 95 ± 2%, and compliance was 99 ± 1%. Home-HIT increased [Formula: see text] by 7% (P = 0.017) and decreased insulin dose by 13% (P = 0.012). Blood glucose concentration did not change from baseline to immediately or 1 h post Home-HIT. Qualitative perceptions of Home-HIT and the virtual-monitoring system were positive, supporting that the intervention successfully removed exercise barriers in people with type 1 diabetes.Conclusions: Virtually monitored Home-HIT resulted in high adherence alongside increased [Formula: see text] and decreased insulin dose. [ABSTRACT FROM AUTHOR]

Key points: Reduced carbohydrate (CHO) availability before and after exercise may augment endurance training‐induced adaptations of human skeletal muscle, as mediated via modulation of cell signalling pathways.However, it is not known whether such responses are mediated by CHO restriction, energy restriction or a combination of both.In recovery from a twice per day training protocol where muscle glycogen concentration is maintained within 200–350 mmol kg−1 dry weight (dw), we demonstrate that acute post‐exercise CHO and energy restriction (i.e. < 24 h) does not potentiate potent cell signalling pathways that regulate hallmark adaptations associated with endurance training.In contrast, consuming CHO before, during and after an acute training session attenuated markers of bone resorption, effects that are independent of energy availability.Whilst the enhanced muscle adaptations associated with CHO restriction may be regulated by absolute muscle glycogen concentration, the acute within‐day fluctuations in CHO availability inherent to twice per day training may have chronic implications for bone turnover. We examined the effects of post‐exercise carbohydrate (CHO) and energy availability (EA) on potent skeletal muscle cell signalling pathways (regulating mitochondrial biogenesis and lipid metabolism) and indicators of bone metabolism. In a repeated measures design, nine males completed a morning (AM) and afternoon (PM) high‐intensity interval (HIT) (8 × 5 min at 85% V̇O2 peak) running protocol (interspersed by 3.5 h) under dietary conditions of (1) high CHO availability (HCHO: CHO ∼12 g kg−1, EA∼ 60 kcal kg−1 fat free mass (FFM)), (2) reduced CHO but high fat availability (LCHF: CHO ∼3 (−1, EA∼ 60 kcal kg−1 FFM) or (3), reduced CHO and reduced energy availability (LCAL: CHO ∼3 g kg−1, EA∼ 20 kcal kg−1 FFM). Muscle glycogen was reduced to ∼200 mmol kg−1 dw in all trials immediately post PM HIT (P < 0.01) and remained lower at 17 h (171, 194 and 316 mmol kg−1 dw) post PM HIT in LCHF and LCAL (P < 0.001) compared to HCHO. Exercise induced comparable p38MAPK phosphorylation (P < 0.05) immediately post PM HIT and similar mRNA expression (all P < 0.05) of PGC‐1α, p53 and CPT1 mRNA in HCHO, LCHF and LCAL. Post‐exercise circulating βCTX was lower in HCHO (P < 0.05) compared to LCHF and LCAL whereas exercise‐induced increases in IL‐6 were larger in LCAL (P < 0.05) compared to LCHF and HCHO. In conditions where glycogen concentration is maintained within 200–350 mmol kg−1 dw, we conclude post‐exercise CHO and energy restriction (i.e. < 24 h) does not potentiate cell signalling pathways that regulate hallmark adaptations associated with endurance training. In contrast, consuming CHO before, during and after HIT running attenuates bone resorption, effects that are independent of energy availability and circulating IL‐6. Key points: Reduced carbohydrate (CHO) availability before and after exercise may augment endurance training‐induced adaptations of human skeletal muscle, as mediated via modulation of cell signalling pathways.However, it is not known whether such responses are mediated by CHO restriction, energy restriction or a combination of both.In recovery from a twice per day training protocol where muscle glycogen concentration is maintained within 200–350 mmol kg−1 dry weight (dw), we demonstrate that acute post‐exercise CHO and energy restriction (i.e. < 24 h) does not potentiate potent cell signalling pathways that regulate hallmark adaptations associated with endurance training.In contrast, consuming CHO before, during and after an acute training session attenuated markers of bone resorption, effects that are independent of energy availability.Whilst the enhanced muscle adaptations associated with CHO restriction may be regulated by absolute muscle glycogen concentration, the acute within‐day fluctuations in CHO availability inherent to twice per day training may have chronic implications for bone turnover. [ABSTRACT FROM AUTHOR]

Key points: Obesity and sedentary behaviour are associated with capillary rarefaction and impaired muscle microvascular vasoreactivity, due to reduced nitric oxide bioavailability.Low‐volume high‐intensity interval training (HIT) is a time‐efficient alternative to traditional moderate‐intensity continuous training (MICT), but its effect on the muscle microvasculature has not been studied.The applicability of current laboratory‐ and gym‐based HIT protocols for obese individuals with low fitness and mobility has been disputed by public health experts, who cite the strenuous nature and complex protocols as major barriers. Therefore, we developed a virtually supervised HIT protocol targeting this group that can be performed at home without equipment (Home‐HIT).This study is the first to show that 12 weeks of virtually supervised Home‐HIT in obese individuals with elevated cardiovascular disease risk leads to similar increases in capillarisation and eNOS/NAD(P)Hoxidase protein ratio within the muscle microvascular endothelium as virtually supervised home‐based MICT and laboratory‐based HIT, while reducing many of the major barriers to exercise. This study investigated the effect of a novel virtually supervised home‐based high‐intensity interval training (HIT) (Home‐HIT) intervention in obese individuals with elevated cardiovascular disease (CVD) risk on capillarisation and muscle microvascular eNOS/NAD(P)Hoxidase ratio. Thirty‐two adults with elevated CVD risk (age 36 ± 10 years; body mass index 34.3 ± 5 kg m−2; V̇O2 peak 24.6 ± 5.7 ml kg min−1), completed one of three 12‐week training programmes: Home‐HIT (n = 9), laboratory‐based supervised HIT (Lab‐HIT; n = 10) or virtually supervised home‐based moderate‐intensity continuous training (Home‐MICT; n = 13). Muscle biopsies were taken before and after training to assess changes in vascular enzymes, capillarisation, mitochondrial density, intramuscular triglyceride content and GLUT4 protein expression using quantitative immunofluorescence microscopy. Training increased V̇O2 peak (P < 0.001), whole‐body insulin sensitivity (P = 0.033) and flow‐mediated dilatation (P < 0.001), while aortic pulse wave velocity decreased (P < 0.001) in all three groups. Immunofluorescence microscopy revealed comparable increases in total eNOS content in terminal arterioles and capillaries (P < 0.001) in the three conditions. There was no change in eNOS ser1177 phosphorylation (arterioles P = 0.802; capillaries P = 0.311), but eNOS ser1177/eNOS content ratio decreased significantly following training in arterioles and capillaries (P < 0.001). Training decreased NOX2 content (arterioles P < 0.001; capillaries P < 0.001), but there was no change in p47phox content (arterioles P = 0.101; capillaries P = 0.345). All measures of capillarisation increased (P < 0.05). There were no between‐group differences. Despite having no direct supervision during exercise, virtually supervised Home‐HIT resulted in comparable structural and endothelial enzymatic changes in the skeletal muscle microvessels to the traditional training methods. We provide strong evidence that Home‐HIT is an effective novel strategy to remove barriers to exercise and improve health in an obese population at risk of CVD. Key points: Obesity and sedentary behaviour are associated with capillary rarefaction and impaired muscle microvascular vasoreactivity, due to reduced nitric oxide bioavailability.Low‐volume high‐intensity interval training (HIT) is a time‐efficient alternative to traditional moderate‐intensity continuous training (MICT), but its effect on the muscle microvasculature has not been studied.The applicability of current laboratory‐ and gym‐based HIT protocols for obese individuals with low fitness and mobility has been disputed by public health experts, who cite the strenuous nature and complex protocols as major barriers. Therefore, we developed a virtually supervised HIT protocol targeting this group that can be performed at home without equipment (Home‐HIT).This study is the first to show that 12 weeks of virtually supervised Home‐HIT in obese individuals with elevated cardiovascular disease risk leads to similar increases in capillarisation and eNOS/NAD(P)Hoxidase protein ratio within the muscle microvascular endothelium as virtually supervised home‐based MICT and laboratory‐based HIT, while reducing many of the major barriers to exercise. [ABSTRACT FROM AUTHOR]

Passive heat therapy (PHT) has been proposed as an alternative intervention to moderate-intensity continuous training (MICT) in individuals who are unable or unwilling to exercise. This study aimed to make the first comparison of the effect of PHT and MICT on 1) skeletal muscle capillarization and endothelial-specific endothelial nitric oxide synthase (eNOS) content and 2) mitochondrial density, glucose transporter 4 (GLUT4), and intramuscular triglyceride (IMTG) content. Twenty young sedentary males (21 ± 1 yr, body mass index 25 ± 1 kg/m2) were allocated to either 6 wk of PHT (n = 10; 40-50 min at 40°C in a heat chamber, 3×/wk) or MICT (n = 10; time-matched cycling at ~65% V̇o2peak). Muscle biopsies were taken from the vastus lateralis muscle before and after training. Immunofluorescence microscopy was used to assess changes in skeletal muscle mitochondrial density (mitochondrial marker cytochrome c oxidase subunit 4), GLUT4, and IMTG content, capillarization, and endothelial-specific eNOS content. V̇o2peak and whole body insulin sensitivity were also assessed. PHT and MICT both increased capillary density (PHT 21%; MICT 12%), capillary-fiber perimeter exchange index (PHT 15%; MICT 12%) (P < 0.05), and endothelial-specific eNOS content (PHT 8%; MICT 12%) (P < 0.05). However, unlike MICT (mitochondrial density 40%; GLUT4 14%; IMTG content 70%) (P < 0.05), PHT did not increase mitochondrial density (11%, P = 0.443), GLUT4 (7%, P = 0.217), or IMTG content (1%, P = 0.957). Both interventions improved aerobic capacity (PHT 5%; MICT 7%) and whole body insulin sensitivity (PHT 15%; MICT 36%) (P < 0.05). Six-week PHT in young sedentary males increases skeletal muscle capillarization and eNOS content to a similar extent as MICT; however, unlike MICT, PHT does not affect skeletal muscle mitochondrial density, GLUT4, or IMTG content. [ABSTRACT FROM AUTHOR]

We examined the effects of graded muscle glycogen on exercise capacity and modulation of skeletal muscle signaling pathways associated with the regulation of mitochondrial biogenesis. In a repeated-measures design, eight men completed a sleep-low, train-low model comprising an evening glycogen-depleting cycling protocol followed by an exhaustive exercise capacity test [8 x 3 min at 80% peak power output (PPO), followed by 1-min efforts at 80% PPO until exhaustion] the subsequent morning. After glycogen-depleting exercise, subjects ingested a total of 0 g/kg (L-CHO), 3.6 g/kg (M-CHO), or 7.6 g/kg (H-CHO) of carbohydrate (CHO) during a 6-h period before sleeping, such that exercise was commenced the next morning with graded (P < 0.05) muscle glycogen concentrations (means ± SD: L-CHO: 88 ± 43, M-CHO: 185 ± 62, H-CHO: 278 ± 47 mmol/kg dry wt). Despite differences (P < 0.05) in exercise capacity at 80% PPO between trials (L-CHO: 18 ± 7, M-CHO: 36 ± 3, H-CHO: 44 ± 9 min), exercise induced comparable AMPKThr172 phosphorylation (~4- fold) and PGC-1α mRNA expression (~5-fold) after exercise and 3 h after exercise, respectively. In contrast, neither exercise nor CHO availability affected the phosphorylation of p38MAPKThr180/Tyr182 or CaMKIIThr268 or mRNA expression of p53, Tfam, CPT-1, CD36, or PDK4. Data demonstrate that when exercise is commenced with muscle glycogen < 300 mmol/kg dry wt, further graded reductions of 100 mmol/kg dry weight impair exercise capacity but do not augment skeletal muscle cell signaling. NEW & NOTEWORTHY We provide novel data demonstrating that when exercise is commenced with muscle glycogen below 300 mmol/kg dry wt (as achieved with the sleep-low, train-low model) further graded reductions in preexercise muscle glycogen of 100 mmol/kg dry wt reduce exercise capacity at 80% peak power output by 20-50% but do not augment skeletal muscle cell signaling. [ABSTRACT FROM AUTHOR]

Key points: Hormone‐sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) are the key enzymes involved in intramuscular triglyceride (IMTG) lipolysis. In isolated rat skeletal muscle, HSL translocates to IMTG‐containing lipid droplets (LDs) following electrical stimulation, but whether HSL translocation occurs in human skeletal muscle during moderate‐intensity exercise is currently unknown. Perilipin‐2 (PLIN2) and perilipin‐5 (PLIN5) proteins have been implicated in regulating IMTG lipolysis by interacting with HSL and ATGL in cell culture and rat skeletal muscle studies. This study investigated the hypothesis that HSL (but not ATGL) redistributes to LDs during moderate‐intensity exercise in human skeletal muscle, and whether the localisation of these lipases with LDs was affected by the presence of PLIN proteins on the LDs. HSL preferentially redistributed to PLIN5‐associated LDs whereas ATGL distribution was not altered with exercise; this is the first study to illustrate the pivotal step of HSL redistribution to PLIN5‐associated LDs following moderate‐intensity exercise in human skeletal muscle. Abstract: Hormone‐sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) control skeletal muscle lipolysis. ATGL is present on the surface of lipid droplets (LDs) containing intramuscular triglyceride (IMTG) in both the basal state and during exercise. HSL translocates to LD in ex vivo electrically stimulated rat skeletal muscle. Perilipin‐2‐ and perilipin‐5‐associated lipid droplets (PLIN2+ and PLIN5+ LDs) are preferentially depleted during exercise in humans, indicating that these PLINs may control muscle lipolysis. We aimed to test the hypothesis that in human skeletal muscle in vivo HSL (but not ATGL) is redistributed to PLIN2+ and PLIN5+ LDs during moderate‐intensity exercise. Muscle biopsies from 8 lean trained males (age 21 ± 1 years, BMI 22.6 ± 1.2 kg m−2 and V ̇ O 2 peak 48.2 ± 5.0 ml min−1 kg−1) were obtained before and immediately following 60 min of cycling exercise at ∼59% V ̇ O 2 peak . Cryosections were stained using antibodies targeting ATGL, HSL, PLIN2 and PLIN5. LDs were stained using BODIPY 493/503. Images were obtained using confocal immunofluorescence microscopy and object‐based colocalisation analyses were performed. Following exercise, HSL colocalisation to LDs increased (P < 0.05), and was significantly greater to PLIN5+ LDs (+53%) than to PLIN5− LDs (+34%) (P < 0.05), while the increases in HSL colocalisation to PLIN2+ LDs (+16%) and PLIN2− LDs (+28%) were not significantly different. Following exercise, the fraction of LDs colocalised with ATGL (0.53 ± 0.04) did not significantly change (P < 0.05) and was not affected by PLIN association to the LDs. This study presents the first evidence of exercise‐induced HSL redistribution to LDs in human skeletal muscle and identifies PLIN5 as a facilitator of this mechanism. [ABSTRACT FROM AUTHOR]

Mechanisms mediating postexercise cold-induced increases in PGC-1α gene expression in human skeletal muscle are yet to be fully elucidated but may involve local cooling effects on AMPK and p38 MAPK-related signaling and/or increased systemic β-adrenergic stimulation. Therefore, we aimed to examine whether postexercise cold water immersion enhancement of PGC-1α mRNA is mediated through local or systemic mechanisms. Ten subjects completed acute cycling (8 × 5 min at ~80% peak power output) followed by seated-rest (CON) or single-leg cold water immersion (CWI; 10 min, 8°C). Muscle biopsies were obtained preexercise, postexercise, and 3 h postexercise from a single limb in the CON condition but from both limbs in CWI [thereby providing tissue from a CWI and nonimmersed limb (NOT)]. Muscle temperature decreased up to 2 h postexercise following CWI (−5°C) in the immersed limb, with lesser changes observed in CON and NOT (−3°C, P < 0.05). No differences between limbs were observed in p38 MAPK phosphorylation at any time point (P < 0.05), whereas a significant interaction effect was present for AMPK phosphorylation (P = 0.031). Exercise (CON) increased gene expression of PGC-1α 3 h postexercise (~5-fold, P < 0.001). CWI augmented PGC-1α expression above CON in both the immersed (CWI; ~9-fold, P = 0.003) and NOT limbs (~12-fold, P = 0.001). Plasma normetanephrine concentration was higher in CWI vs. CON immediately postimmersion (860 vs. 665 pmol/l, P = 0.034). We report for the first time that local cooling of the immersed limb evokes transcriptional control of PGC-1α in the nonimmersed limb, suggesting increased systemic β-adrenergic activation of AMPK may mediate, in part, postexercise cold induction of PGC-1α mRNA. NEW & NOTEWORTHY We report for the first time that postexercise cold water immersion of one limb also enhances PGC-1α expression in a contralateral, nonimmersed limb. We suggest that increased systemic β-adrenergic stimulation, and not localized cooling per se, exerts regulatory effects on local signaling cascades, thereby modulating PGC-1α expression. Therefore, these data have important implications for research designs that adopt contralateral, nonimmersed limbs as a control condition while also increasing our understanding of the potential mechanisms underpinning cold-mediated PGC-1α responses. [ABSTRACT FROM AUTHOR]

It is well described that increasing free fatty acids (FFAs) to high physiological levels reduces insulin sensitivity. In sedentary humans, intramyocellular lipid (IMCL) is inversely related to insulin sensitivity. Since muscle fiber composition affects muscle metabolism, whether FFAs induce IMCL accumulation in a fiber type-specific manner remains unknown. We hypothesized that in the setting of acute FFA elevation by lipid infusion within the context of a hyperinsulinemic-euglycemic clamp, IMCL will preferentially accumulate in type 1 fibers. Normal-weight participants (n = 57, mean ± SE: age 24 ± 0.6 yr, BMI 22.2 ± 0.3 kg/m2) who were either endurance trained or sedentary by self-report were recruited from the University of Minnesota (n = 31, n = 15 trained) and University of Pittsburgh (n = 26, n = 14 trained). All participants underwent a hyperinsulinemic-euglycemic clamp in the context of a 6-h infusion of either lipid or glycerol control. A vastus lateralis muscle biopsy was obtained at baseline and end-infusion (6 h). The muscle biopsies were processed and analyzed at the University of Pittsburgh for fiber type-specific IMCL accumulation by Oil-Red-O staining. Regardless of training status, acute elevation of FFAs to high physiological levels (~400-600 meq/l) increased IMCL preferentially in type 1 fibers (+35 ± 11% compared with baseline, +29 ± 11% compared with glycerol control: P < 0.05). The increase in IMCL correlated with a decline in insulin sensitivity as measured by the hyperinsulinemic-euglycemic clamp (r= -0.32, P < 0.01) independent of training status. Regardless of training status, increase of FFAs to a physiological range within the context of hyperinsulinemia shows preferential IMCL accumulation in type 1 fibers. [ABSTRACT FROM AUTHOR]

Using an amalgamation of previously studied "train-low" paradigms, we tested the effects of reduced carbohydrate (CHO) but high leucine availability on cell-signaling responses associated with exercise-induced regulation of mitochondrial biogenesis and muscle protein synthesis (MPS). In a repeated-measures crossover design, 11 males completed an exhaustive cycling protocol with high CHO availability before, during, and after exercise (HIGH) or alternatively, low CHO but high protein (leucine enriched) availability (LOW + LEU). Muscle glycogen was different (P < 0.05) pre-exercise (HIGH: 583 ± 158, LOW + LEU: 271 ± 85 mmol kg-1 dw) but decreased (P < 0.05) to comparable levels at exhaustion (-100 mmol kg-1 dw). Despite differences (P < 0.05) in exercise capacity (HIGH: 158 ± 29, LOW + LEU: 100 ± 17 min), exercise induced (P < 0.05) comparable AMPKa2 (3-4-fold) activity, PGC-1a (13-fold), p53 (2-fold), Tfam (1.5-fold), SIRT1 (1.5-fold), Atrogin 1 (2-fold), and MuRF1 (5-fold) gene expression at 3 h post-exercise. Exhaustive exercise suppressed p70S6K activity to comparable levels immediately post-exercise (-20 fmol min-1 mg-1). Despite elevated leucine availability post-exercise, p70S6K activity remained suppressed (P < 0.05) 3 h postexercise in LOW + LEU (28 ± 14 fmol min-1 mg-1), whereas muscle glycogen resynthesis (40 mmol kg-1 dw h-1) was associated with elevated (P < 0.05) p70S6K activity in HIGH (53 ± 30 fmol min-1 mg-1). We conclude: (1) CHO restriction before and during exercise induces "work-efficient" mitochondrial-related cell signaling but; (2) post-exercise CHO and energy restriction maintains p70S6K activity at basal levels despite feeding leucineenriched protein. Our data support the practical concept of "fuelling for the work required" as a potential strategy for which to amalgamate train-low paradigms into periodized training programs. [ABSTRACT FROM AUTHOR]

Background: Excessive sitting time is a risk factor for cardiovascular disease mortality and morbidity independent of physical activity. This aim of this study was to evaluate the impact of a sit-stand workstation on sitting time, and vascular, metabolic and musculoskeletal outcomes in office workers, and to investigate workstation acceptability and feasibility.Methods: A two-arm, parallel-group, individually randomised controlled trial was conducted in one organisation. Participants were asymptomatic full-time office workers aged ≥18 years. Each participant in the intervention arm had a sit-stand workstation installed on their workplace desk for 8 weeks. Participants in the control arm received no intervention. The primary outcome was workplace sitting time, assessed at 0, 4 and 8 weeks by an ecological momentary assessment diary. Secondary behavioural, cardiometabolic and musculoskeletal outcomes were assessed. Acceptability and feasibility were assessed via questionnaire and interview. ANCOVA and magnitude-based inferences examined intervention effects relative to controls at 4 and 8 weeks. Participants and researchers were not blind to group allocation.Results: Forty-seven participants were randomised (intervention n = 26; control n = 21). Relative to the control group at 8 weeks, the intervention group had a beneficial decrease in sitting time (-80.2 min/8-h workday (95 % CI = -129.0, -31.4); p = 0.002), increase in standing time (72.9 min/8-h workday (21.2, 124.6); p = 0.007) and decrease in total cholesterol (-0.40 mmol/L  (-0.79, -0.003); p = 0.049). No harmful changes in musculoskeletal discomfort/pain were observed relative to controls, and beneficial changes in flow-mediated dilation and diastolic blood pressure were observed. Most participants self-reported that the workstation was easy to use and their work-related productivity did not decrease when using the device. Factors that negatively influenced workstation use were workstation design, the social environment, work tasks and habits.Conclusion: Short-term use of a feasible sit-stand workstation reduced daily sitting time and led to beneficial improvements in cardiometabolic risk parameters in asymptomatic office workers. These findings imply that if the observed use of the sit-stand workstations continued over a longer duration, sit-stand workstations may have important ramifications for the prevention and reduction of cardiometabolic risk in a large proportion of the working population.Trial Registration: ClinicalTrials.gov NCT02496507 . [ABSTRACT FROM AUTHOR]

Background: Within a controlled laboratory environment, high-intensity interval training (HIT) elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT). It is currently unclear how HIT can be applied effectively in a real-world environment. Purpose: To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, group-based gym setting, elicits improvements in aerobic capacity (VO2max), cardio-metabolic risk and psychological health which are comparable to MICT. Methods: Ninety physically inactive volunteers (42±11 y, 27.7±4.8 kg.m-2) were randomly assigned to HIT or MICT group exercise classes. HIT consisted of repeated sprints (15–60 seconds, >90% HRmax) interspersed with periods of recovery cycling (≤25 min.session-1, 3 sessions.week-1). MICT participants performed continuous cycling (~70% HRmax, 30–45 min.session-1, 5 sessions.week-1). VO2max, markers of cardio-metabolic risk, and psychological health were assessed pre and post-intervention. Results: Mean weekly training time was 55±10 (HIT) and 128±44 min (MICT) (p<0.05), with greater adherence to HIT (83±14% vs. 61±15% prescribed sessions attended, respectively; p<0.05). HIT improved VO2max, insulin sensitivity, reduced abdominal fat mass, and induced favourable changes in blood lipids (p<0.05). HIT also induced beneficial effects on health perceptions, positive and negative affect, and subjective vitality (p<0.05). No difference between HIT and MICT was seen for any of these variables. Conclusions: HIT performed in a real-world gym setting improves cardio-metabolic risk factors and psychological health in physically inactive adults. With a reduced time commitment and greater adherence than MICT, HIT offers a viable and effective exercise strategy to target the growing incidence of metabolic disease and psychological ill-being associated with physical inactivity. [ABSTRACT FROM AUTHOR]

Objective: The effects of RT on muscle mass, strength, and insulin sensitivity are well established, but the underlying mechanisms are only partially understood. The main aim of this study was to investigate whether RT induces changes in endothelial enzymes of the muscle microvasculature, which would increase NO bioavailability and could contribute to improved insulin sensitivity. Methods: Eight previously sedentary males (age 20 ± 0.4 years, BMI 24.5 ± 0.9 kg/m²) completed six weeks of RT 3x/week. Muscle biopsies were taken from the m. vastus lateralis and microvascular density; and endothelial-specific eNOS content, eNOS Ser1177 phosphorylation, and NOX2 content were assessed pre- and post-RT using quantitative immunofluorescence microscopy. Whole-body insulin sensitivity (measured as Matsuda Index), microvascular Kf (functional measure of the total available endothelial surface area), and arterial stiffness (AIx, central, and pPWV) were also measured. Results: Measures of microvascular density, microvascular Kf, microvascular eNOS content, basal eNOS phosphorylation, and endothelial NOX2 content did not change from pre-RT to post-RT. RT increased insulin sensitivity (p < 0.05) and reduced resting blood pressure and AIx (p < 0.05), but did not change central or pPWV. Conclusions: RT did not change any measure of muscle microvascular structure or function. [ABSTRACT FROM AUTHOR]

Increases in insulin-mediated glucose uptake following endurance training ( ET) and sprint interval training ( SIT) have in part been attributed to concomitant increases in glucose transporter 4 ( GLUT4) protein content in skeletal muscle. This study used an immunofluorescence microscopy method to investigate changes in subcellular GLUT4 distribution and content following ET and SIT. Percutaneous muscle biopsy samples were taken from the m. vastus lateralis of 16 sedentary males in the overnight fasted state before and after 6 weeks of ET and SIT. An antibody was fully validated and used to show large (> 1 μm) and smaller (<1 μm) GLUT4-containing clusters. The large clusters likely represent trans-Golgi network stores and the smaller clusters endosomal stores and GLUT4 storage vesicles ( GSVs). Density of GLUT4 clusters was higher at the fibre periphery especially in perinuclear regions. A less dense punctate distribution was seen in the rest of the muscle fibre. Total GLUT4 fluorescence intensity increased in type I and type II fibres following both ET and SIT. Large GLUT4 clusters increased in number and size in both type I and type II fibres, while the smaller clusters increased in size. The greatest increases in GLUT4 fluorescence intensity occurred within the 1 μm layer immediately adjacent to the PM. The increase in peripheral localisation and protein content of GLUT4 following ET and SIT is likely to contribute to the improvements in glucose homeostasis observed after both training modes. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Cocks M, Shepherd SO, Shaw CS, Achten J, Costa ML, Wagenmakers AJM. Immunofluorescence microscopy to assess enzymes controlling nitric oxide availability and microvascular blood flow in muscle. Microcirculation 19: 642-651, 2012. Abstract Objective: The net production of NO by the muscle microvascular endothelium is a key regulator of muscle microvascular blood flow. Here, we describe the development of a method to quantify the protein content and phosphorylation of endothelial NO synthase (eNOS content and eNOS ser1177 phosphorylation) and NAD(P)H oxidase expression. Methods: Human muscle cryosections were stained using antibodies targeting eNOS, p-eNOS ser1177 and NOX2 in combination with markers of the endothelium and the sarcolemma. Quantitation was achieved by analyzing fluorescence intensity within the area stained positive for the microvascular endothelium. Analysis was performed in duplicate and repeated five times to investigate CV. In addition, eight healthy males (age 21 ± 1 year, BMI 24.4 ± 1.0 kg/m2) completed one hour of cycling exercise at ∼65% VO2max. Muscle biopsies were taken from the m. vastus lateralis before and immediately after exercise and analyzed using the new methods. Results: The CV of all methods was between 6.5 and 9.5%. Acute exercise increased eNOS serine1177 phosphorylation (fold change 1.29 ± 0.05, p < 0.05). Conclusions: These novel methodologies will allow direct investigations of the molecular mechanisms underpinning the microvascular responses to insulin and exercise, the impairments that occur in sedentary, obese and elderly individuals and the effect of lifestyle interventions. [ABSTRACT FROM AUTHOR]