Selective overexpression of Toll-like receptor-4 in skeletal muscle impairs metabolic adaptation to high-fat feeding.

Toll-like receptor-4 (TLR-4) is elevated in skeletal muscle of obese humans, and data from our laboratory have shown that activation of TLR-4 in skeletal muscle via LPS results in decreased fatty acid oxidation (FAO). The purpose of this study was to determine whether overexpression of TLR-4 in skeletal muscle alters mitochondrial function and whole body metabolism in the context of a chow and high-fat diet. C57BL/6J mice (males, 6-8 mo of age) with skeletal muscle-specific overexpression of the TLR-4 (mTLR-4) gene were created and used for this study. Isolated mitochondria and whole muscle homogenates from rodent skeletal muscle (gastrocnemius and quadriceps) were investigated. TLR-4 overexpression resulted in a significant reduction in FAO in muscle homogenates; however, mitochondrial respiration and reactive oxygen species (ROS) production did not appear to be affected on a standard chow diet. To determine the role of TLR-4 overexpression in skeletal muscle in response to high-fat feeding, mTLR-4 mice and WT control mice were fed low- and high-fat diets for 16 wk. The high-fat diet significantly decreased FAO in mTLR-4 mice, which was observed in concert with elevated body weight and fat, greater glucose intolerance, and increase in production of ROS and cellular oxidative damage compared with WT littermates. These findings suggest that TLR-4 plays an important role in the metabolic response in skeletal muscle to high-fat feeding.

Assessing the Impact of a Shinrin-Yoku (Forest Bathing) Intervention on Physician/Healthcare Professional Burnout: A Randomized, Controlled Trial.

Professional healthcare worker burnout is a crisis in the United States healthcare system. This crisis can be viewed at any level, from the national to local communities, but ultimately, must be understood at the level of the individual who is caring for patients. Thus, interventions to reduce burnout symptoms must prioritize the mental health of these individuals by alleviating some of the symptoms of depression, grief, and anxiety that accompany burnout. The practice of Shinrin-Yoku (Forest Bathing) is a specific evidence-based practice which research has shown can improve an individual's mental health and, when performed in a group, can support a sense of social connection. We investigated the impact of a three-hour, guided Shinrin-Yoku (Forest Bathing) nature-based intervention on burnout symptoms among physicians and other healthcare workers by using a randomized, controlled trial. The Oldenburg Burnout Inventory (OLBI) and Mini-Z assessments were used to collect baseline burnout scores and participants were randomized into the intervention group, which completed the assessment again after the Shinrin-Yoku walk, or into a control group, which completed the assessments again after a day off from any clinical duties. A total of 34 participants were enrolled in the intervention group and a total of 22 participants were enrolled in the control group. Ultimately, no statistically significant differences were detected between the pre-test and post-test scores for the intervention group or between the post-test scores of the intervention group compared to the control group. However, the subjective responses collected from participants after participating in the Shinrin-Yoku walk overwhelmingly reported decreased feelings of stress and increased mental wellbeing. This raises important questions about the difference between symptoms of burnout and other aspects of mental health, as well as the limitations of a one-time nature-based intervention on levels of chronic burnout symptoms. Thus, further research on the effects of engaging healthcare providers in an ongoing practice of Shinrin-Yoku is warranted.

Muscle-Specific Deletion of Toll-like Receptor 4 Impairs Metabolic Adaptation to Wheel Running in Mice.

PURPOSE: Toll-like receptor 4 (TLR4) is an inflammatory receptor expressed ubiquitously in immune cells as well as skeletal muscle and other metabolic tissues. Skeletal muscle develops favorable inflammation-mediated metabolic adaptations from exercise training. Multiple inflammatory myokines, downstream from TLR4, are proposed links to the metabolic benefits of exercise. In addition, activation of TLR4 alters skeletal muscle substrate preference. The role of skeletal muscle TLR4 (mTLR4) in exercise metabolism has not previously been investigated. Herein, we aimed to specifically test the significance of mTLR4 to exercise-induced metabolic adaptations. METHODS: We developed a novel muscle-specific TLR4 knockout (mTLR4-/-) mouse model on C57BL/6J background. Male mTLR4-/- mice and wild-type (WT) littermates were compared under sedentary (SED) and voluntary wheel running (WR) conditions for 4 wk. RESULTS: mTLR4 deletion revealed marked reductions in downstream interleukin-1 receptor-associated kinase-4 (IRAK4) phosphorylation. In addition, the disruption of mTLR4 signaling prominently blunted the metabolic adaptations in WR-mTLR4-/- mice as opposed to substantial improvements exhibited by the WT counterparts. Voluntary WR in WT mice, relative to SED, resulted in significant increases in skeletal muscle fatty acid oxidation, glucose oxidation, and associated mitochondrial enzyme activities, all of which were not significantly changed in mTLR4-/- mice. CONCLUSIONS: This study introduces a novel mTLR4-/- mouse model and identifies mTLR4 as an immunomodulatory effector of exercise-induced metabolic adaptations in skeletal muscle.

Probiotic supplementation attenuates increases in body mass and fat mass during high-fat diet in healthy young adults.

OBJECTIVE: The objective was to determine the effects of the probiotic, VSL#3, on body and fat mass, insulin sensitivity, and skeletal muscle substrate oxidation following 4 weeks of a high-fat diet. METHODS: Twenty non-obese males (18-30 years) participated in the study. Following a 2-week eucaloric control diet, participants underwent dual X-ray absorptiometry to determine body composition, an intravenous glucose tolerance test to determine insulin sensitivity, and a skeletal muscle biopsy for measurement of in vitro substrate oxidation. Subsequently, participants were randomized to receive either VSL#3 or placebo daily during 4 weeks of consuming a High-fat (55% fat), hypercaloric diet (+1,000 kcal day(-1) ). Participants repeated all measurements following the intervention. RESULTS: Body mass (1.42 ± 0.42 kg vs. 2.30 ± 0.28 kg) and fat mass (0.63 ± 0.09 kg vs. 1.29 ± 0.27 kg) increased less following the High-fat diet in the VSL#3 group compared with placebo. However, there were no significant changes in insulin sensitivity or in vitro skeletal muscle pyruvate and fat oxidation with the High-fat diet or VSL#3. CONCLUSIONS: VSL#3 supplementation appears to have provided some protection from body mass gain and fat accumulation in healthy young men consuming a High-fat and high-energy diet.

Breast cancer prevention in community clinics: will low-income Latina patients participate in clinical trials?

BACKGROUND: Latinas have low rates of participation in breast cancer prevention trials. We evaluated the feasibility and effectiveness of a randomized trial of brief counseling and print materials compared to print materials alone to increase intent to participate in a breast cancer prevention trial. METHODS: We enrolled 450 women Spanish-speaking women from three urban community primary care clinics. The outcome was intent, defined as might, probably, or definitely would enroll in the trial. We also examined results using a more stringent definition restricted to probably and definitely intend to participate. RESULTS: The trial was feasible within these busy clinics, and 96% of women agreed to participate. The level of breast cancer knowledge was fairly high (66% correct answers), but understanding about clinical trials was lower (40.5% correct answers). Using the less stringent criteria for intent, 72% of women stated that they intended to enroll in the STAR trial if eligible, but rates of intent decreased to 52% with framing that included medication side effects and 45% if uterine cancer was mentioned (P < 0.01 for trend). Using the more stringent definition, slightly fewer than half of the women indicated an interest in participating, with the same trend towards decreasing intent with increasing presentation of side effects. The intervention was only effective using the less stringent definition and if no side effects were mentioned (77% intent vs. 67% in the intervention and control groups, respectively, P = 0.03). Intention was independently associated with greater worry about breast cancer and younger age, but not acculturation or knowledge. CONCLUSIONS: Latina women are interested in participating in clinical trials to prevent breast cancer, although interest declines with increasing discussion of side effects. Unfortunately, brief education only increased rates of intention using the least stringent definition and when no side effects were presented in framing the question. Future work should focus on qualitative research to understand the theoretical foundations of preventive health behaviors in this population.