Reduced Energy Expenditure Research Articles

The novel chimeric multi-agonist peptide (GEP44) reduces energy intake and body weight in male and female diet-induced obese mice in a glucagon-like peptide-1 receptor-dependent manner.

We recently reported that a novel chimeric peptide (GEP44) targeting both the glucagon-like peptide-1 receptor (GLP-1R) and neuropeptide Y1- and Y2 receptor (Y1R and Y2R) reduced energy intake and body weight (BW) in diet-induced obese (DIO) rats. We hypothesized that GEP44 reduces energy intake and BW primarily through a GLP-1R dependent mechanism. To test this hypothesis, GLP-1R+/+ mice and GLP-1R null (GLP-1R-/-) mice were fed a high fat diet for 4 months to elicit diet-induced obesity prior to undergoing a sequential 3-day vehicle period, 3-day drug treatment (5, 10, 20 or 50 nmol/kg; GEP44 vs the selective GLP-1R agonist, exendin-4) and a 3-day washout. Energy intake, BW, core temperature and activity were measured daily. GEP44 (10, 20 and 50 nmol/kg) reduced BW after 3-day treatment in DIO male GLP-1R+/+ mice by -1.5 ± 0.6, -1.3 ± 0.4 and -1.9 ± 0.4 grams, respectively (P<0.05), with similar effects being observed in female GLP-1R+/+ mice. These effects were absent in male and female DIO GLP-1R-/- mice suggesting that GLP-1R signaling contributes to GEP44-elicited reduction of BW. Further, GEP44 decreased energy intake in both male and female DIO GLP-1R+/+ mice, but GEP44 appeared to produce more consistent effects across multiple doses in males. In GLP-1R-/- mice, the effects of GEP44 on energy intake were only observed in males and not females, suggesting that GEP44 may reduce energy intake, in part, through a GLP-1R independent mechanism in males. In addition, GEP44 reduced core temperature and activity in both male and female GLP-1R+/+ mice suggesting that it may also reduce energy expenditure. Lastly, we show that GEP44 reduced fasting blood glucose in DIO male and female mice through GLP-1R. Together, these findings support the hypothesis that the chimeric peptide, GEP44, reduces energy intake, BW, core temperature, and glucose levels in male and female DIO mice primarily through a GLP-1R dependent mechanism.

REDD1 Is a Promising Therapeutic Target to Combat the Development of Diabetes Complications: A Report on Research Supported by Pathway to Stop Diabetes.

The stress response protein regulated in development and DNA damage response 1 (REDD1) has emerged as a key player in the pathogenesis of diabetes. Diabetes upregulates REDD1 in a variety of insulin-sensitive tissues, where the protein acts to inhibit signal transduction downstream of the insulin receptor. REDD1 functions as a cytosolic redox sensor that suppresses Akt/mTORC1 signaling to reduce energy expenditure in response to cellular stress. Whereas a transient increase in REDD1 contributes to an adaptive cellular response, chronically elevated REDD1 levels are implicated in disease progression. Recent studies highlight the remarkable benefits of both whole-body and tissue-specific REDD1 deletion in preclinical models of type 1 and type 2 diabetes. In particular, REDD1 is necessary for the development of glucose intolerance and the consequent rise in oxidative stress and inflammation. Herein, we review studies that support a role for chronically elevated REDD1 levels in the development of diabetic complications, reflect on limitations of prior therapeutic approaches targeting REDD1 in patients, and discuss potential opportunities for future interventions to improve the lives of people living with diabetes. This article is part of a series of Perspectives that report on research funded by the American Diabetes Association Pathway to Stop Diabetes program.

Torpor use in the wild by one of the world's largest bats.

Torpor is widespread among bats presumably because most species are small, and torpor greatly reduces their high mass-specific resting energy expenditure, especially in the cold. Torpor has not been recorded in any bat species larger than 50 g, yet in theory could be beneficial even in the world's largest bats (flying-foxes; Pteropus spp.) that are exposed to adverse environmental conditions causing energy bottlenecks. We used temperature telemetry to measure body temperature in wild-living adult male grey-headed flying-foxes (P. poliocephalus; 799 g) during winter in southern Australia. We found that all individuals used torpor while day-roosting, with minimum body temperature reaching 27°C. Torpor was recorded following a period of cool, wet and windy weather, and on a day with the coldest maximum air temperature, suggesting it is an adaptation to reduce energy expenditure during periods of increased thermoregulatory costs and depleted body energy stores. A capacity for torpor among flying-foxes has implications for understanding their distribution, behavioural ecology and life history. Furthermore, our discovery increases the body mass of bats known to use torpor by more than tenfold and extends the documented use of this energy-saving strategy under wild conditions to all bat superfamilies, with implications for the evolutionary maintenance of torpor among bats and other mammals.

TIRZEPATIDE: Trending ‘Weight loss’ Drug– Potential Influence in Tackling Obesity Epidemic

Obesity is a chronic disease that is associated with severe complications. A lifestyle involving an increased appetite and reduced energy expenditure promotes weight gain. A better understanding of the endocrine regulation of appetite has led to the development of newer medications for the treatment of obesity. Among these medications is an incretin-based drug named tirzepatide. Many studies have been conducted in obese, insulin-resistant, and lipid-diet-fed mice to evaluate the effect of tirzepatide and its combination of GIP and GLP-1 agonism demonstrated higher anorectic activity by increasing satiety and satiation, decreasing liking for high-fat diets and decreasing sweet taste reference as compared to the effects of semaglutide. Adverse effects of mild gastrointestinal events and decreased appetite were reported with tirzepatide (which reduced after some time) than with placebo. In phase 3 SURPASS clinical trial optimized dose escalation scheme was adopted to improve gastrointestinal tolerability with an initial low dose of tirzepatide. The results of the SURPASS-1 trial showed significant improvement in glycemic control and durable bodyweight reductions with all the doses (3 doses) of tirzepatide compared to placebo in type 2 diabetic patients along with diet and exercise. Weight loss occurred regardless of whether participants reported any gastrointestinal adverse events and did not elevate over the period.

Starvation-induced changes in the proteome and transcriptome of the salivary glands of leech (Hirudo nipponia).

Hirudo nipponia is an important medicinal animal in China. Its salivary gland secretions contain a variety of protein bioactive substances. Investigations of its salivary glands are of great significance in the study of the medicinal value and mechanism of leech secretions. Illumina RNA-Seq technology was used to perform transcriptome sequencing of salivary gland tissue of H. nipponia under starvation (D30) and fed (D0) states. A total of 2,650 differentially expressed genes (DEGs) were screened. Using the label-free protein quantification technique and bioinformatics analysis, the expression of differentially expressed proteins (DEPs) in the salivary gland tissue of H. nipponia was compared. A total of 2,021 proteins were identified, among which 181 proteins were differentially expressed between the starvation and fed states, with 72 significantly upregulated and 109 significantly downregulated. The salivary glands of H. nipponia synthesized protein-based active substances after 30 days of starvation and adapted to the starvation environment by weakening respiratory activity and reducing metabolic activity to reduce energy expenditure. Energy was produced by glycolysis and the tricarboxylic acid cycle for the synthesis of substances such as antibiotics. This study combined transcriptome and proteome sequencing data to provide a data reference for an in-depth study of the regulatory mechanism of salivary gland secretions of H. nipponia under starvation stress by analyzing DEGs and DEPs.

SMIM1 absence is associated with reduced energy expenditure and excess weight

Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments. We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1-/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan. We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure. This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them. This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.

Effects of combining a high-intensity interval training programme with a standard programme on mobility and function in lower limb amputees.

High-energy expenditure during walking is one of the most important limiting factors for lower limb amputees. Although several physical training methods have been proposed to reduce energy expenditure, little is known about the effects of high-intensity interval training in lower limb amputees. This study aimed to test the effects of a 6-week high-intensity interval training protocol in subjects with lower limb amputation on walking distance, physiological cost of walking, and functional mobility. A quasi-experimental pre and post-study included 13 subjects with lower limb amputation. They performed 12 sessions of a high-intensity interval training protocol with a frequency of 2 days/week for 6 weeks. Walking distance, physiological cost of walking, and functional mobility before and after the training protocol were assessed. Walking distance increased from 204.48 to 229.09 m ( P = 0.003), physiological cost of walking decreased from 0.66 to 0.31 beats/m ( P = 0.001), and functional mobility improved from 30.38 to 33.61 points ( P = 0.001). High-intensity interval training improved walking distance, physiological cost of walking, and functional mobility in subjects with lower limb amputation.

Detecting genetic gain and loss events in terms of protein domain: Method and implementation

Continuous gain and loss of genes are the primary driving forces of bacterial evolution and environmental adaptation. Studying bacterial evolution in terms of protein domain, which is the fundamental function and evolutionary unit of proteins, can provide a more comprehensive understanding of bacterial differentiation and phenotypic adaptation processes. Therefore, we proposed a phylogenetic tree-based method for detecting genetic gain and loss events in terms of protein domains. Specifically, the method focuses on a single domain to trace its evolution process or on multiple domains to investigate their co-evolution principles. This novel method was validated using 122 Shigella isolates. We found that the loss of a significant number of domains was likely the main driving force behind the evolution of Shigella, which could reduce energy expenditure and preserve only the most essential functions. Additionally, we observed that simultaneously gained and lost domains were often functionally related, which can facilitate and accelerate phenotypic evolutionary adaptation to the environment. All results obtained using our method agree with those of previous studies, which validates our proposed method.

Dependency task offloading in semantic communications

In the realm of advanced wireless communications, the significance of semantic communication has become increasingly pronounced, particularly in its focus on the meaning and efficiency of information transmission. Given the voluminous nature of task data and the intricacy of task interconnections, executing semantic segmentation tasks directly on user-end devices often falls short due to limitations in processing power. Leveraging mobile edge computing, however, presents a strategic enhancement in performing semantic segmentation tasks by delegating computational workloads to proximal devices, thus diminishing latency and reducing energy expenditure. This document delineates a task offloading framework aimed at refining the management of interdependent tasks, thereby boosting the efficiency of processing complex tasks within environments of semantic communication. The framework abstracts tasks in the form of directed acyclic graphs (DAG) and approaches the optimization challenge through a Markov Decision Process (MDP), targeting an optimal balance between task completion, delay reduction, and energy savings. To adapt to fluctuating network conditions, a novel approach employing the Deep Deterministic Policy Gradient (DTO-DDPG) algorithm is introduced for optimization decision-making. Our empirical tests underscore the framework’s capacity to significantly elevate task completion rates while simultaneously decreasing both energy consumption and latency in scenarios of semantic communication.

Coverage Planning for UVC Irradiation: Robot Surface Disinfection Based on Swarm Intelligence Algorithm.

Ultraviolet (UV) radiation has been widely utilized as a disinfection strategy to effectively eliminate various pathogens. The disinfection task achieves complete coverage of object surfaces by planning the motion trajectory of autonomous mobile robots and the UVC irradiation strategy. This introduces an additional layer of complexity to path planning, as every point on the surface of the object must receive a certain dose of irradiation. Nevertheless, the considerable dosage required for virus inactivation often leads to substantial energy consumption and dose redundancy in disinfection tasks, presenting challenges for the implementation of robots in large-scale environments. Optimizing energy consumption of light sources has become a primary concern in disinfection planning, particularly in large-scale settings. Addressing the inefficiencies associated with dosage redundancy, this study proposes a dose coverage planning framework, utilizing MOPSO to solve the multi-objective optimization model for planning UVC dose coverage. Diverging from conventional path planning methodologies, our approach prioritizes the intrinsic characteristics of dose accumulation, integrating a UVC light efficiency factor to mitigate dose redundancy with the aim of reducing energy expenditure and enhancing the efficiency of robotic disinfection. Empirical trials conducted with autonomous disinfecting robots in real-world settings have corroborated the efficacy of this model in deactivating viruses.

Monitoring post-spawning movement, habitat use, and survival of adult anadromous rainbow smelt using acoustic telemetry in a New Hampshire estuary.

Anadromous rainbow smelt (Osmerus mordax, [Mitchill 1814]) are found along the northeast Atlantic coastline of North America, with their range now limited to north of Cape Cod, Massachusetts, USA. Although their anadromous life cycles are described broadly, gaps remain regarding how adult rainbow smelt use estuaries post-spawning, including movement behaviors, habitats used, and specific timing of emigration to coastal waters. In spring 2021, we used acoustic telemetry to characterize movements during and after the spawning season of rainbow smelt captured in tributaries to Great Bay, New Hampshire, USA, a large estuarine system near the southern edge of their range. Forty-four adult rainbow smelt (n = 35 male, n = 9 female) were tagged with Innovasea V5 180-kHz transmitters and an array of 22,180 kHz VR2W receivers were deployed throughout Great Bay to detect movements of tagged fish from March to October 2021. Rainbow smelt were detected 14,186 times on acoustic telemetry receivers, with 41 (93%) of the tagged individuals being detected at least once post-tagging. Individuals were detected moving between tributaries, revealing that rainbow smelt can use multiple rivers during the spawning season (March-April). Mark-recapture Cormack-Jolly-Seber models estimated 83% (95% confidence interval 66%-92%) of rainbow smelt survived to the mainstem Piscataqua River, and a minimum of 50% (22 of 44) reached the seaward-most receivers and were presumed to have survived emigration. Most individuals that survived remained in the estuary for multiple weeks (average = 19.47 ± 1.99 standard error days), displaying extended use of estuarine environments. Downstream movements occurred more frequently during ebb tides and upstream movements with flood tides, possibly a mechanism to reduce energy expenditures. Fish emigrated from the estuary by mid-May to the coastal Gulf of Maine. Our results underscore that rainbow smelt need access to a variety of habitats, including multiple tributaries and high-quality estuarine habitat, to complete their life cycle.

Transfer learning improves predictions in lignin content of Chinese fir based on Raman spectra

Lignin in biomass plays significant role in substitution of synthetic polymer and reduction of energy expenditure, and the lignin content was usually determined by wet chemical methods. However, the methods' heavy workload, low efficiency, huge consumption of chemicals and use of toxic reagents render them unsuitable for sustainable development and environmental protection. Chinese fir, a prevalent angiosperm tree, holds immense importance for various industries. Since our previous work found that Raman spectroscopy could accurately predict the lignin content in poplar, we propose that the lignin content of Chinese fir can be estimated by similar strategy. The results suggested that the peak at 2895 cm−1 is the optimal choice of internal standard peak and algorithm of XGBoost demonstrates the highest accuracy among all algorithms. Furthermore, transfer learning was successfully introduced to enhance the accuracy and robustness of the model. Ultimately, we report that a machine learning algorithm, combining transfer learning with XGBoost or LightGBM, offers an accurate, high-efficiency and environmental friendly method for predicting the lignin content of Chinese fir using Raman spectra.

Brown adipose tissue metabolism in women is dependent on ovarian status.

In rodents, loss of estradiol (E2) reduces brown adipose tissue (BAT) metabolic activity. Whether E2 impacts BAT activity in women is not known. BAT oxidative metabolism was measured in premenopausal (n = 27; 35 ± 9 yr; body mass index = 26.0 ± 5.3 kg/m2) and postmenopausal (n = 25; 51 ± 8 yr; body mass index = 28.0 ± 5.0 kg/m2) women at room temperature and during acute cold exposure using [11C]acetate with positron emission tomography coupled with computed tomograph. BAT glucose uptake was also measured during acute cold exposure using 2-deoxy-2-[18F]fluoro-d-glucose. To isolate the effects of ovarian hormones from biological aging, measurements were repeated in a subset of premenopausal women (n = 8; 40 ± 4 yr; BMI = 28.0 ± 7.2 kg/m2) after 6 mo of gonadotropin-releasing hormone agonist therapy to suppress ovarian hormones. At room temperature, there was no difference in BAT oxidative metabolism between premenopausal (0.56 ± 0.31 min-1) and postmenopausal women (0.63 ± 0.28 min-1). During cold exposure, BAT oxidative metabolism (1.28 ± 0.85 vs. 0.91 ± 0.63 min-1, P = 0.03) and net BAT glucose uptake (84.4 ± 82.5 vs. 29.7 ± 31.4 nmol·g-1·min-1, P < 0.01) were higher in premenopausal than postmenopausal women. In premenopausal women who underwent gonadotropin-releasing hormone agonist, cold-stimulated BAT oxidative metabolism was reduced to a similar level (from 1.36 ± 0.66 min-1 to 0.91 ± 0.41 min-1) to that observed in postmenopausal women (0.91 ± 0.63 min-1). These results provide the first evidence in humans that reproductive hormones are associated with BAT oxidative metabolism and suggest that BAT may be a target to attenuate age-related reduction in energy expenditure and maintain metabolic health in postmenopausal women.NEW & NOTEWORTHY In rodents, loss of estrogen reduces brown adipose tissue (BAT) activity. Whether this is true in humans is not known. We found that BAT oxidative metabolism and glucose uptake were lower in postmenopausal compared to premenopausal women. In premenopausal women who underwent ovarian suppression to reduce circulating estrogen, BAT oxidative metabolism was reduced to postmenopausal levels. Thus the loss of ovarian function in women leads to a reduction in BAT metabolic activity independent of age.

Smooth muscle cell-derived Cxcl12 directs macrophage accrual and sympathetic innervation to control thermogenic adipose tissue

Sympathetic innervation of brown adipose tissue (BAT) controls mammalian adaptative thermogenesis. However, the cellular and molecular underpinnings contributing to BAT innervation remain poorly defined. Here, we show that smooth muscle cells (SMCs) support BAT growth, lipid utilization, and thermogenic plasticity. Moreover, we find that BAT SMCs express and control the bioavailability of Cxcl12. SMC deletion of Cxcl12 fosters brown adipocyte lipid accumulation, reduces energy expenditure, and increases susceptibility to diet-induced metabolic dysfunction. Mechanistically, we find that Cxcl12 stimulates CD301+ macrophage recruitment and supports sympathetic neuronal maintenance. Administering recombinant Cxcl12 to obese mice or leptin-deficient (Ob/Ob) mice is sufficient to boost macrophage presence and drive sympathetic innervation to restore BAT morphology and thermogenic responses. Altogether, our data reveal an SMC chemokine-dependent pathway linking immunological infiltration and sympathetic innervation as a rheostat for BAT maintenance and thermogenesis.

Alpha-2-adrenergic agonists reduce resting energy expenditure in humans during external cooling

ABSTRACT Intravenous alpha-2-adrenergic receptor agonists reduce energy expenditure and lower the temperature when shivering begins in humans, allowing a decrease in core body temperature. Because there are few data about similar effects from oral drugs, we tested whether single oral doses of the sedative dexmedetomidine (1 µg/kg sublingual or 4 µg/kg swallowed) or the muscle relaxant tizanidine (8 mg or 16 mg), combined with surface cooling, reduce energy expenditure and core body temperature in humans. A total of 26 healthy participants completed 41 one-day laboratory studies measuring core body temperature using an ingested telemetry capsule and measuring energy expenditure using indirect calorimetry for up to 6 hours after drug ingestion. Dexmedetomidine induced a median 13% – 19% peak reduction and tizanidine induced a median 15% – 22% peak reduction in energy expenditure relative to baseline. Core body temperature decreased a median of 0.5°C – 0.6°C and 0.5°C – 0.7°C respectively. Decreases in temperature occurred after peak reductions in energy expenditure. Energy expenditure increased with a decrease in core temperature in control participants but did not occur after 4 µg/kg dexmedetomidine or 16 mg tizanidine. Plasma levels of dexmedetomidine but not tizanidine were related to mean temperature change. Decreases in heart rate, blood pressure, respiratory rate, cardiac stroke volume index, and cardiac index were associated with the change in metabolic rate after higher drug doses. We conclude that both oral dexmedetomidine and oral tizanidine reduce energy expenditure and allow decrease in core temperature in humans.

Coupling and Quantifying Sustainability and Resilience in Intelligent Buildings

Over recent years, the sustainability and resilience concept has increased its significance in the construction industry. Sustainability is associated with implementing best practices in the construction industry, while resilience is the adaptability and tolerance of systems in harsh conditions. The concepts are learned in the construction process. Moreover, building automation is growing rapidly, and buildings are becoming increasingly dependent on complex systems and technology and susceptible to unanticipated failure. Though sustainability and resilience concepts are interlinked, limited research quantifies their combination, resulting in a limited comprehension of how both concepts interact during application by developers in a smart building. Therefore, this study has established a financial model that employs Net Present Value (NPV) in studying the inference and clampdown of investment in both concepts. NPV was estimated using indirect and direct costs and benefits derived from the continuous integration of sustainability and resilience in a smart building. To quantify sustainability, its three components had to be quantified. Reduced energy expenditure and government environmental incentives were used to calculate the environmental component. Workers’ cost savings, fire insurance cost savings, and additional system maintenance costs were used to calculate the economic component. The social component of sustainability measured hard-to-quantify attributes like productivity, indoor environment quality, reputation, extra profit, services, and safety. To quantify them, a survey and RII method were used. The two concepts were then coupled by estimating the benefits and costs of installing and keeping resilience tools in design that are sustainable in the smart building and the impact study on the NPV outcome. Application of the design model was also carried out on four smart buildings that were selected in Dubai. The result indicated that coupling sustainable approaches and resilience yields higher NPV by at least 22%. Nevertheless, for NPV to be maintained positively and reduce the cost of failure, faulty detection tools should be assimilated while designing sustainable and smart buildings. The findings of this study will contribute to the benefit of other researchers, developers, investors, managers, engineers, and anyone who is involved in the design or construction process of intelligent buildings.

Uncertainty-aware autonomous sensing with deep reinforcement learning

Constructing an accurate representation model of phenomena with fewer measurements is a fundamental challenge in the Internet of Things. Leveraging sparse sensing policies to select the most informative measurements is a prominent technique for addressing resource constraints. However, designing such sensing policies requires significant domain knowledge and involves manually fine-tuned heuristics that are task-specific and often non-adaptive. In this work, we propose reducing manual-engineering efforts in designing sensing policies by using an automated approach based on deep reinforcement learning. Guided by an uncertainty-aware prediction model, the sensors learn sensing behaviors autonomously by optimizing an application goal formulated in the reward function based on the measured peaks-over-threshold. We apply the proposed approach in two use cases of monitoring air quality and indoor noise and show the adaptability and transferability of the learned policies. Compared to conventional periodic sensing methods, our results achieve, on average, an increased detection in periods of interest by 78.5% and 357.3% while reducing energy expenditure by 14.3% and 7.6% for air quality and noise monitoring, respectively. Additionally, the resulting representation models are more credible, as measured by various metrics of probabilistic modeling.

Learning shapes the development of migratory behavior

How animals refine migratory behavior over their lifetime (i.e., the ontogeny of migration) is an enduring question with important implications for predicting the adaptive capacity of migrants in a changing world. Yet, our inability to monitor the movements of individuals from early life onward has limited our understanding of the ontogeny of migration. The exploration-refinement hypothesis posits that learning shapes the ontogeny of migration in long-lived species, resulting in greater exploratory behavior early in life followed by more rapid and direct movement during later life. We test the exploration-refinement hypothesis by examining how white storks (Ciconia ciconia) balance energy, time, and information as they develop and refine migratory behavior during the first years of life. Here, we show that young birds reduce energy expenditure during flight while also increasing information gain by exploring new places during migration. As the birds age and gain more experience, older individuals stop exploring new places and instead move more quickly and directly, resulting in greater energy expenditure during migratory flight. During spring migration, individuals innovated novel shortcuts during the transition from early life into adulthood, suggesting a reliance on spatial memory acquired through learning. These incremental refinements in migratory behavior provide support for the importance of individual learning within a lifetime in the ontogeny of long-distance migration.

P21-activated kinase-1 signaling is required to preserve adipose tissue homeostasis and cardiac function.

While P21-activated kinase-1 (PAK1) has been extensively studied in relation to cardiovascular health and glucose metabolism, its roles within adipose tissue and cardiometabolic diseases are less understood. In this study, we explored the effects of PAK1 deletion on energy balance, adipose tissue homeostasis, and cardiac function utilizing a whole-body PAK1 knockout (PAK1-/-) mouse model. Our findings revealed that body weight differences between PAK1-/- and WT mice emerged at 9 weeks of age, with further increases observed at 12 weeks. Furthermore, PAK1-/- mice displayed increased fat mass and decreased lean mass at 12 weeks, indicating a shift towards adiposity. In conjunction with the increased body weight, PAK1-/- mice had increased food intake and reduced energy expenditure. At a mechanistic level, PAK1 deletion boosted the expression of lipogenic markers while diminishing thermogenic markers expression in adipose tissues, contributing to reduced energy expenditure and the overall obesogenic phenotype. Moreover, our findings highlighted a significant impact on cardiac function following PAK1 deletion, including alterations in calcium kinetics and compromised systolic and lusitropy functions. In summary, our study emphasizes the significant role of PAK1 in weight regulation and cardiac function, enriching our comprehension of heart health and metabolism. These findings could potentially facilitate the identification of novel therapeutic targets in cardiometabolic diseases.

Correspondence between Expected, Perceived, and Measured Effects of BoNT-A Treatment in Calf Muscles among Children and Adolescents with Cerebral Palsy: A Mixed Methods Study.

(1) Background: Our study explores the relationship between expected, perceived, and measured effects of botulinum toxin A (BoNT-A) treatment and saline (placebo) in children and adolescents with cerebral palsy (CP) in the calf muscles of 20 children and adolescents with cerebral palsy (CP), aged 4-15 years, using the Gross Motor Function Classification System (GMFCS) I-II. (2) Methods: A mixed methods parallel database design was used. Quantitative and qualitative data were collected at baseline and four weeks after treatment. The primary quantitative measure was gross energy cost (EC) during walking, obtained from a 5-Minute Walk Test (5MWT), while qualitative semi-structured interviews were performed with each parent and child/adolescent individually. (3) Results: Four weeks after treatment, we did not find any correspondence between expected, measured, and perceived effects. Interestingly, parental perceptions of treatment effects were more consistent than the measured outcomes. We also observed a connection between parental treatment expectations and perceived effects, often related to reduced energy expenditure. Children tended to view their parents as treatment experts and had fewer expectations and perceptions themselves. (4) Conclusions: These findings support the importance of child-centered care, which entails actively listening to children's expectations and perceptions during the treatment process.