Higher resistance training volume offsets muscle hypertrophy nonresponsiveness in older individuals.

The magnitude of muscle hypertrophy in response to resistance training (RT) is highly variable between individuals (response heterogeneity). Manipulations in RT variables may modulate RT-related response heterogeneity; yet, this remains to be determined. Using a within-subject unilateral design, we aimed to investigate the effects of RT volume manipulation on whole muscle hypertrophy [quadriceps muscle cross-sectional area (qCSA)] among nonresponders and responders to a low RT dose (single-set). We also investigated the effects of RT volume manipulation on muscle strength in these responsiveness groups. Eighty-five older individuals [41M/44F, age = 68 ± 4 yr; body mass index (BMI) = 26.4 ± 3.7 kg/m2] had one leg randomly allocated to a single (1)-set and the contralateral leg allocated to four sets of unilateral knee-extension RT at 8-15 repetition maximum (RM) for 10-wk 2 days/wk. Pre- and postintervention, participants underwent magnetic resonance imaging (MRI) and unilateral knee-extension 1-RM strength testing. MRI typical error (2× TE = 3.27%) was used to classify individuals according to responsiveness patterns. n = 51 were classified as nonresponders (≤2× TE) and n = 34 as responders (>2× TE) based on pre- to postintervention change qCSA following the single-set RT protocol. Nonresponders to single-set training showed a dose response, with significant time × set interactions for qCSA and 1-RM strength, indicating greater gains in response to the higher volume prescription (time × set: P < 0.05 for both outcomes). Responders improved qCSA (time: P < 0.001), with a tendency toward higher benefit from the four sets RT protocol (time × set: P = 0.08); on the other hand, 1-RM increased similarly irrespectively of RT volume prescription (time × set: P > 0.05). Our findings support the use of higher RT volume to mitigate nonresponsiveness among older adults.NEW & NOTEWORTHY Using a within-subject unilateral design, we demonstrated that increasing resistance training (RT) volume may be a simple, effective strategy to improve muscle hypertrophy and strength gains among older adults who do not respond to low-volume RT. In addition, it could most likely be used to further improve hypertrophic outcomes in responders.

Muscle Inflammation Susceptibility: A Potential Phenotype for Guiding Precision Rehabilitation After Total Hip Arthroplasty in End-Stage Osteoarthritis.

The progression of osteoarthritis of the hip to its end stage and ultimately to total hip arthroplasty (THA) is complex; the multifactorial pathophysiology involves myriad collaborating tissues in and around the diseased joint. We have named the heightened state of periarticular muscle inflammation at the time of surgery "muscle inflammation susceptibility" (MuIS) because it is distinct from systemic inflammation. In this review article, we discuss how MuIS and heightened atrophy-associated signaling in the periarticular skeletal muscles may contribute to reduced muscle mass, impaired muscle quality (ie, through fibrosis), and a muscle microenvironment that challenges regenerative capacity and thus functional recovery from THA. We also review directions for future research that should advance understanding of the key determinants of precision for optimized success of THA for each individual.

Dynamic transcriptomic responses to divergent acute exercise stimuli in young adults.

Acute exercise elicits dynamic transcriptional changes that, when repeated, form the fundamental basis of health, resilience, and performance adaptations. While moderate-intensity endurance training combined with conventional resistance training (traditional, TRAD) is often prescribed and recommended by public health guidance, high-intensity training combining maximal-effort intervals with intensive, limited-rest resistance training is a time-efficient alternative that may be used tactically (HITT) to confer similar benefits. Mechanisms of action of these distinct stimuli are incompletely characterized and have not been directly compared. We assessed transcriptome-wide responses in skeletal muscle and circulating extracellular vesicles (EVs) to a single exercise bout in young adults randomized to TRAD (n = 21, 12 M/9 F, 22 ± 3 yr) or HITT (n = 19, 11 M/8 F, 22 ± 2 yr). Next-generation sequencing captured small, long, and circular RNA in muscle and EVs. Analysis identified differentially expressed transcripts (|log2FC|>1, FDR ≤ 0.05) immediately (h0, EVs only), h3, and h24 postexercise within and between exercise protocols. In aaddition, all apparently responsive transcripts (FDR < 0.2) underwent singular value decomposition to summarize data structures into latent variables (LVs) to deconvolve molecular expression circuits and interregulatory relationships. LVs were compared across time and exercise protocol. TRAD, a longer but less intense stimulus, generally elicited a stronger transcriptional response than HITT, but considerable overlap and key differences existed. Findings reveal shared and unique molecular responses to the exercise stimuli and lay groundwork toward establishing relationships between protein-coding genes and lesser-understood transcripts that serve regulatory roles following exercise. Future work should advance the understanding of these circuits and whether they repeat in other populations or following other types of exercise/stress.NEW & NOTEWORTHY We examined small and long transcriptomics in skeletal muscle and serum-derived extracellular vesicles before and after a single exposure to traditional combined exercise (TRAD) and high-intensity tactical training (HITT). Across 40 young adults, we found more consistent protein-coding gene responses to TRAD, whereas HITT elicited differential expression of microRNA enriched in brain regions. Follow-up analysis revealed relationships and temporal dynamics across transcript networks, highlighting potential avenues for research into mechanisms of exercise response and adaptation.

Muscle transcriptomic circuits linked to periarticular physiology in end-stage osteoarthritis.

The ability of individuals with end-stage osteoarthritis (OA) to functionally recover from total joint arthroplasty is highly inconsistent. The molecular mechanisms driving this heterogeneity have yet to be elucidated. Furthermore, OA disproportionately impacts females, suggesting a need for identifying female-specific therapeutic targets. We profiled the skeletal muscle transcriptome in females with end-stage OA (n = 20) undergoing total knee or hip arthroplasty using RNA-Seq. Single-gene differential expression (DE) analyses tested for DE genes between skeletal muscle overlaying the surgical (SX) joint and muscle from the contralateral (CTRL) leg. Network analyses were performed using Pathway-Level Information ExtractoR (PLIER) to summarize genes into latent variables (LVs), i.e., gene circuits, and link them to biological pathways. LV differences in SX versus CTRL muscle and across sources of muscle tissue (vastus medialis, vastus lateralis, or tensor fascia latae) were determined with ANOVA. Linear models tested for associations between LVs and muscle phenotype on the SX side (inflammation, function, and integrity). DE analysis revealed 360 DE genes (|Log2 fold-difference| ≥ 1, FDR ≤ 0.05) between the SX and CTRL limbs, many associated with inflammation and lipid metabolism. PLIER analyses revealed circuits associated with protein degradation and fibro-adipogenic cell gene expression. Muscle inflammation and function were linked to an LV associated with endothelial cell gene expression highlighting a potential regulatory role of endothelial cells within skeletal muscle. These findings may provide insight into potential therapeutic targets to improve OA rehabilitation before and/or following total joint replacement.

Effects of end-stage osteoarthritis on markers of skeletal muscle Long INterspersed Element-1 activity.

OBJECTIVE: Long INterspersed Element-1 (L1) is an autonomous transposable element in the genome. L1 transcripts that are not reverse transcribed back into the genome can accumulate in the cytoplasm and activate an inflammatory response via the cyclic GMP-AMP (cGAS)-STING pathway. We examined skeletal muscle L1 markers as well as STING protein levels in 10 older individuals (63 ± 11 y, BMI = 30.2 ± 6.8 kg/m2) with end-stage osteoarthritis (OA) undergoing total hip (THA, n = 4) or knee (TKA, n = 6) arthroplasty versus 10 young, healthy comparators (Y, 22 ± 2 y, BMI = 23.2 ± 2.5 kg/m2). For OA, muscle was collected from surgical (SX) and contralateral (CTL) sides whereas single vastus lateralis samples were collected from Y. RESULTS: L1 mRNA was higher in CTL and SX compared to Y (p < 0.001 and p = 0.001, respectively). Protein expression was higher in SX versus Y for ORF1p (p = 0.002) and STING (p = 0.022). While these data are preliminary due to limited n-sizes and the lack of a BMI-matched younger control group, higher L1 mRNA expression, ORF1p and STING protein are evident in older versus younger adults. More research is needed to determine whether cGAS-STING signaling contributes to heightened muscle inflammation during aging and/or OA.

State of Knowledge on Molecular Adaptations to Exercise in Humans: Historical Perspectives and Future Directions.

For centuries, regular exercise has been acknowledged as a potent stimulus to promote, maintain, and restore healthy functioning of nearly every physiological system of the human body. With advancing understanding of the complexity of human physiology, continually evolving methodological possibilities, and an increasingly dire public health situation, the study of exercise as a preventative or therapeutic treatment has never been more interdisciplinary, or more impactful. During the early stages of the NIH Common Fund Molecular Transducers of Physical Activity Consortium (MoTrPAC) Initiative, the field is well-positioned to build substantially upon the existing understanding of the mechanisms underlying benefits associated with exercise. Thus, we present a comprehensive body of the knowledge detailing the current literature basis surrounding the molecular adaptations to exercise in humans to provide a view of the state of the field at this critical juncture, as well as a resource for scientists bringing external expertise to the field of exercise physiology. In reviewing current literature related to molecular and cellular processes underlying exercise-induced benefits and adaptations, we also draw attention to existing knowledge gaps warranting continued research effort. © 2021 American Physiological Society. Compr Physiol 12:3193-3279, 2022.

Whey Protein Supplementation Effects on Body Composition, Performance, and Blood Biomarkers During Army Initial Entry Training.

This study assesses if a lower dose of whey protein can provide similar benefits to those shown in previous work supplementing Army Initial Entry Training (IET) Soldiers with two servings of whey protein (WP) per day. Eighty-one soldiers consumed one WP or a calorie matched carbohydrate (CHO) serving/day during IET (WP: n = 39, height = 173 ± 8 cm, body mass = 76.8 ± 12.8 kg, age = 21 ± 3 years; CHO: n = 42, 175 ± 8 cm, 77.8 ± 15.3 kg, 23 ± 4 years). Physical performance (push-ups, sit-ups, and a two-mile run) was assessed during weeks two and eight. All other measures (dietary intake, body composition, blood biomarkers) at weeks one and nine. There was a significant group difference for fat mass (p = 0.044) as WP lost 2.1 ± 2.9 kg and had a moderate effect size (Cohen's d: -0.24), whereas the CHO group lost 0.9 ± 2.5 kg and had only a small effect size (d: -0.1). There was no significant group-by-time interaction on fat-free mass (p = 0.069). WP gained 1.2 ± 2.4 (d: 0.1) and CHO gained 0.1 ± 3 (d: 0) kg of FFM on average. There was a significant group by week 1-fat free mass interaction (p = 0.003) indicating individuals with higher initial fat-free mass benefitted more from WP. There were no group differences for push-up (p = 0.514), sit-up (p = 0.429) or run (p = 0.313) performance. For all biomarkers there was a significant effect of time as testosterone (p < 0.01), testosterone to cortisol ratio (p = 0.39), and IGF-1 (p < 0.01) increased across training and cortisol (p = 0.04) and IL-6 (p < 0.01) decreased. There were no differences in groups across IET for any of the biomarkers. We conclude one WP serving is beneficial for FM and for FFM in soldiers with high baseline FFM but may not significantly alter biomarker response or physical performance of IET soldiers who have high relative dietary protein intakes.

Perioperative assessment of muscle inflammation susceptibility in patients with end-stage osteoarthritis.

Many individuals with end-stage osteoarthritis (OA) undergo elective total hip/knee arthroplasty (THA/TKA) to relieve pain, improve mobility and quality of life. However, ∼30% suffer long-term mobility impairment following surgery. This may be in part due to muscle inflammation susceptibility (MuIS+), an overt proinflammatory pathology localized to skeletal muscle surrounding the diseased joint, present in some patients with TKA/THA. We interrogated the hypothesis that MuIS+ status results in a perturbed perioperative gene expression profile and decreases skeletal muscle integrity in patients with end-stage OA. Samples were leveraged from the two-site, randomized, controlled trial R01HD084124, NCT02628795. Participants were dichotomized based on surgical (SX) muscle gene expression of TNFRSF1A (TNF-αR). MuIS+/- samples were probed for gene expression and fibrosis. Paired and independent two-tailed t tests were used to determine differences between contralateral (CTRL) and surgical (SX) limbs and between-subject comparisons, respectively. Significance was declared at P < 0.05. Seventy participants (26M/44F; mean age 62.41 ± 8.86 yr; mean body mass index 31.10 ± 4.91 kg/m2) undergoing THA/TKA were clustered as MuIS+ (n = 24) or MuIS- (n = 46). Lower skeletal muscle integrity (greater fibrosis) exists on the SX versus CTRL limb (P < 0.001). Furthermore, MuIS+ versus MuIS- muscle exhibited higher proinflammatory (IL-6R and TNF-α) and catabolic (TRIM63) gene expression (P < 0.001, P = 0.004, and 0.024 respectively), with a trend for greater fibrosis (P = 0.087). Patients with MuIS+ exhibit more inflammation and catabolic gene expression in skeletal muscle of the SX limb, accompanied by decreased skeletal muscle integrity (Trend). This highlights the impact of MuIS+ status emphasizing the potential value of perioperative MuIS assessment to inform optimal postsurgical care.NEW & NOTEWORTHY This study assessed the skeletal muscle molecular characteristics associated with end-stage osteoarthritis and refined an important phenotype, in some patients, termed muscle inflammation susceptibility (MuIS+) that may be an important consideration following surgery. Furthermore, we provide evidence of differential inflammatory and catabolic gene expression between the contralateral and surgical limbs along with differences between the skeletal muscle surrounding the diseased hip versus knee joints.

Muscle transcriptional networks linked to resistance exercise training hypertrophic response heterogeneity.

The skeletal muscle hypertrophic response to resistance exercise training (RT) is highly variable across individuals. The molecular underpinnings of this heterogeneity are unclear. This study investigated transcriptional networks linked to RT-induced muscle hypertrophy, classified as 1) predictive of hypertrophy, 2) responsive to RT independent of muscle hypertrophy, or 3) plastic with hypertrophy. Older adults (n = 31, 18 F/13 M, 70 ± 4 yr) underwent 14-wk RT (3 days/wk, alternating high-low-high intensity). Muscle hypertrophy was assessed by pre- to post-RT change in mid-thigh muscle cross-sectional area (CSA) [computed tomography (CT), primary outcome] and thigh lean mass [dual-energy X-ray absorptiometry (DXA), secondary outcome]. Transcriptome-wide poly-A RNA-seq was performed on vastus lateralis tissue collected pre- (n = 31) and post-RT (n = 22). Prediction networks (using only baseline RNA-seq) were identified by weighted gene correlation network analysis (WGCNA). To identify Plasticity networks, WGCNA change indices for paired samples were calculated and correlated to changes in muscle size outcomes. Pathway-level information extractor (PLIER) was applied to identify Response networks and link genes to biological annotation. Prediction networks (n = 6) confirmed transcripts previously connected to resistance/aerobic training adaptations in the MetaMEx database while revealing novel member genes that should fuel future research to understand the influence of baseline muscle gene expression on hypertrophy. Response networks (n = 6) indicated RT-induced increase in aerobic metabolism and reduced expression of genes associated with spliceosome biology and type-I myofibers. A single exploratory Plasticity network was identified. Findings support that interindividual differences in baseline gene expression may contribute more than RT-induced changes in gene networks to muscle hypertrophic response heterogeneity. Code/Data: https://github.com/kallavin/MASTERS_manuscript/tree/master.

Markers of Bone Health and Impact of Whey Protein Supplementation in Army Initial Entry Training Soldiers: A Double-Blind Placebo-Controlled Study.

Training civilians to be soldiers is a challenging task often resulting in musculoskeletal injuries, especially bone stress injuries. This study evaluated bone health biomarkers (P1NP/CTX) and whey protein or carbohydrate supplementations before and after Army initial entry training (IET). Ninety male IET soldiers participated in this placebo-controlled, double-blind study assessing carbohydrate and whey protein supplementations. Age and fat mass predicted bone formation when controlling for ethnicity, explaining 44% (p < 0.01) of bone formation variations. Age was the only significant predictor of bone resorption (p = 0.02) when controlling for run, fat, and ethnicity, and these factors together explained 32% of the variance in bone resorption during week one (p < 0.01). Vitamin D increased across training (p < 0.01). There was no group by time interaction for supplementation and bone formation (p = 0.75), resorption (p = 0.73), Vitamin D (p = 0.36), or calcium (p = 0.64), indicating no influence of a supplementation on bone biomarkers across training. Age, fitness, fat mass, and ethnicity were important predictors of bone metabolism. The bone resorption/formation ratio suggests IET soldiers are at risk of stress injuries. Male IET soldiers are mildly to moderately deficient in vitamin D and slightly deficient in calcium throughout training. Whey protein or carbohydrate supplementations did not affect the markers of bone metabolism.

Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson's Disease.

Parkinson's disease (PD) is the most common motor neurodegenerative disease, and neuromuscular function deficits associated with PD contribute to disability. Targeting these symptoms, our laboratory has previously evaluated 16-week high-intensity resistance exercise as rehabilitative training (RT) in individuals with PD. We reported significant improvements in muscle mass, neuromuscular function (strength, power, and motor unit activation), indices of neuromuscular junction integrity, total and motor scores on the unified Parkinson's disease rating scale (UPDRS), and total and sub-scores on the 39-item PD Quality of Life Questionnaire (PDQ-39), supporting the use of RT to reverse symptoms. Our objective was to identify transcriptional networks that may contribute to RT-induced neuromuscular remodeling in PD. We generated transcriptome-wide skeletal muscle RNA-sequencing in 5 participants with PD [4M/1F, 67 ± 2 years, Hoehn and Yahr stages 2 (n = 3) and 3 (n = 2)] before and after 16-week high intensity RT to identify transcriptional networks that may in part underpin RT-induced neuromuscular remodeling in PD. Following RT, 304 genes were significantly upregulated, notably related to remodeling and nervous system/muscle development. Additionally, 402 genes, primarily negative regulators of muscle adaptation, were downregulated. We applied the recently developed Pathway-Level Information ExtractoR (PLIER) method to reveal coordinated gene programs (as latent variables, LVs) that differed in skeletal muscle among young (YA) and old (OA) healthy adults and PD (n = 12 per cohort) at baseline and in PD pre- vs. post-RT. Notably, one LV associated with angiogenesis, axon guidance, and muscle remodeling was significantly lower in PD than YA at baseline and was significantly increased by exercise. A different LV annotated to denervation, autophagy, and apoptosis was increased in both PD and OA relative to YA and was also reduced by 16-week RT in PD. Thus, this analysis identified two novel skeletal muscle transcriptional programs that are dysregulated by PD and aging, respectively. Notably, RT has a normalizing effect on both programs in individuals with PD. These results identify potential molecular transducers of the RT-induced improvements in neuromuscular remodeling and motor function that may aid in optimizing exercise rehabilitation strategies for individuals with PD.

Functional Performance of Firefighters After Exposure to Environmental Conditions and Exercise.

CONTEXT: Slips, trips, and falls are leading causes of musculoskeletal injuries in firefighters. Researchers have hypothesized that heat stress is the major contributing factor to these fireground injuries. OBJECTIVE: To examine the effect of environmental conditions, including hot and ambient temperatures, and exercise on functional and physiological outcome measures, including balance, rectal temperature, and perceived exertion. DESIGN: Randomized controlled clinical trial. SETTING: Laboratory environmental chamber. PATIENTS OR OTHER PARTICIPANTS: A total of 13 healthy, active career firefighters (age = 26 ± 6 years [range = 19-35 years], height = 178.61 ± 4.93 cm, mass = 86.56 ± 16.13 kg). INTERVENTION(S): Independent variables consisted of 3 conditions (exercise in heat [37.41°C], standing in heat [37.56°C], and exercise in ambient temperature [14.24°C]) and 3 data-collection times (preintervention, postintervention, and postrecovery). Each condition was separated from the others by at least 1 week and lasted a maximum of 40 minutes or until the participant reached volitional fatigue or a rectal temperature of 40.0°C. MAIN OUTCOME MEASURE(S): Firefighting-specific functional balance performance index, rectal temperature, and rating of perceived exertion. RESULTS: Exercise in the heat decreased functional balance, increased rectal temperature, and altered the perception of exertion compared with the other intervention conditions. CONCLUSIONS: A bout of exercise in a hot, humid environment increased rectal temperature in a similar way to that reported in the physically active population and negatively affected measures of functional balance. Rather than independently affecting balance, the factors of exercise and heat stress appeared to combine, leading to an increased likelihood of slips, trips, and falls.

Impact of Protein and Carbohydrate Supplementation on Musculoskeletal Injuries in Army Initial Entry Training Soldiers.

This project investigated whey protein and/or carbohydrate supplementation effects on musculoskeletal injury (MSI) outcomes. Four groups of Initial Entry Training soldiers consumed either: (1) one protein (38.6 g, 293 kcal); (2) one carbohydrate (63.4 g, 291 kcal); (3) two protein (77.2 g, 586 kcal); or (4) two carbohydrate servings/day (126.8 g, 582 kcal) after physical training and before bed, or before bed only. Odds Ratio, Chi-square and Wilcoxon ranked-sum test compared supplementation/no supplementation, number of servings, and protein/carbohydrate for MSI and limited/missed duty rates and limited/missed training days. Non-matched pairs group averages were compared to 2015/2016 historical data. Non-supplemented soldiers were approximately 5× more likely to sustain a MSI (χ2 = 58.48, p < 0.001) and 4× more likely to miss training (χ2 = 9.73, p = 0.003) compared to two servings. Non-supplemented soldiers missed five additional training days compared to two servings (W = 6059.5, p = 0.02). Soldiers consuming one serving were approximately 3× more likely to sustain a MSI than two servings (χ2 = 9.55, p = 0.002). There was no difference in limited/missed duty rates or limited/missed training days between consuming one or two servings. There was no difference between consuming one serving versus no supplementation or protein versus carbohydrate supplementation for any outcome variable. Soldiers consuming 2 servings/day of protein or carbohydrate had lower MSI rates, limited/missed duty rates, and limited/ missed training days compared to non-supplemented soldiers.

Effect of Whey Protein Supplementation on Physical Performance and Body Composition in Army Initial Entry Training Soldiers.

We investigated the effects of whey protein (WP) supplementation on body composition and physical performance in soldiers participating in Army Initial Entry Training (IET). Sixty-nine, male United States Army soldiers volunteered for supplementation with either twice daily whey protein (WP, 77 g/day protein, ~580 kcal/day; n = 34, age = 19 ± 1 year, height = 173 ± 6 cm, weight = 73.4 ± 12.7 kg) or energy-matched carbohydrate (CHO) drinks (CHO, 127 g/day carbohydrate, ~580 kcal/day; n = 35, age = 19 ± 1 year, height = 173 ± 5 cm, weight = 72.3 ± 10.9 kg) for eight weeks during IET. Physical performance was evaluated using the Army Physical Fitness Test during weeks two and eight. Body composition was assessed using 7-site skinfold assessment during weeks one and nine. Post-testing push-up performance averaged 7 repetitions higher in the WP compared to the CHO group (F = 10.1, p < 0.001) when controlling for baseline. There was a significant decrease in fat mass at post-training (F = 4.63, p = 0.04), but no significant change in run performance (F = 3.50, p = 0.065) or fat-free mass (F = 0.70, p = 0.41). Effect sizes for fat-free mass gains were large for both the WP (Cohen's d = 0.44) and CHO (Cohen's d = 0.42) groups. WP had a large effect on fat mass (FM) loss (Cohen's d = -0.67), while CHO had a medium effect (Cohen's d = -0.40). Twice daily supplementation with WP improved push-up performance and potentiated reductions in fat mass during IET training in comparison to CHO supplementation.

Effects of protein type and composition on postprandial markers of skeletal muscle anabolism, adipose tissue lipolysis, and hypothalamic gene expression.

BACKGROUND: We examined the acute effects of different dietary protein sources (0.19 g, dissolved in 1 ml of water) on skeletal muscle, adipose tissue and hypothalamic satiety-related markers in fasted, male Wistar rats (~250 g). METHODS: Oral gavage treatments included: a) whey protein concentrate (WPC, n = 15); b) 70:30 hydrolyzed whey-to-hydrolyzed egg albumin (70 W/30E, n = 15); c) 50 W/50E (n = 15); d) 30 W/70E (n = 15); and e) 1 ml of water with no protein as a fasting control (CTL, n = 14). RESULTS: Skeletal muscle analyses revealed that compared to CTL: a) phosphorylated (p) markers of mTOR signaling [p-mTOR (Ser2481) and p-rps6 (Ser235/236)] were elevated 2-4-fold in all protein groups 90 min post-treatment (p < 0.05); b) WPC and 70 W/30E increased muscle protein synthesis (MPS) 104% and 74% 180 min post-treatment, respectively (p < 0.05); and c) 70 W/30E increased p-AMPKα (Thr172) 90 and 180-min post-treatment as well as PGC-1α mRNA 90 min post-treatment. Subcutaneous (SQ) and omental fat (OMAT) analyses revealed: a) 70 W/30 W increased SQ fat phosphorylated hormone-sensitive lipase [p-HSL (Ser563)] 3.1-fold versus CTL and a 1.9-4.4-fold change versus all other test proteins 180 min post-treatment (p < 0.05); and b) WPC, 70 W/30E and 50 W/50E increased OMAT p-HSL 3.8-6.5-fold 180 min post-treatment versus CTL (p < 0.05). 70 W/30E and 30 W/70E increased hypothalamic POMC mRNA 90 min post-treatment versus CTL rats suggesting a satiety-related response may have occurred in the former groups. However, there was a compensatory increase in orexigenic AGRP mRNA in the 70 W/30E group 90 min post-treatment versus CTL rats, and there was a compensatory increase in orexigenic NPY mRNA in the 30 W/70E group 90 min post-treatment versus CTL rats. CONCLUSIONS: Higher amounts of whey versus egg protein stimulate the greatest post-treatment anabolic skeletal muscle response, though test proteins with higher amounts of WPH more favorably affected post-treatment markers related to adipose tissue lipolysis.