The Leadership Experience of Advanced Practice Nurses in a Tertiary Hospital Setting : Focus Group Interview / 중환자간호학회지

Purpose@#: This study aimed to identify and describe the leadership experience of advanced practice nurses (APN). @*Methods@#: Data were collected through five focus group interviews in 2022 with a total of 24 APNs in groups of 4-6 participants. All interviews were recorded, transcribed, and data were analyzed using qualitative content analysis. @*Results@#: Nine categories emerged from three main themes. First, “Roles of APN leadership” comprised a trusted clinical expert, a moderator for the entire team, a resource person for nurturing the next generation, and a change agent for improving clinical practice. Second, “Facilitators and barriers to APN leadership” included ambiguity of APN role, support system, and institutional backing. Third, “Strategies for strengthening APN leadership competencies” comprised systematic leadership education and speaking up for APNs. @*Conclusion@#: APNs are passionate about their expertise and practice, but lack the legal and organizational authority and support to provide successive leadership. Systematic education including leadership and organizational advocacy will enable APN to provide leadership that benefits patients, institutions, and the wider healthcare system.

“Suicide CARE” (Standardized Suicide Prevention Program for Gatekeeper Intervention in Korea): An Update

Objective@#In 2011, “Suicide CARE” (Standardized Suicide Prevention Program for Gatekeeper Intervention in Korea) was originally developed for the early detection of warning signs of suicide completion, since there is a tendency to regard emotional suppression as a virtue of Korean traditional culture. A total of 1.2 million individuals completed the training program of “Suicide CARE” in Korea. @*Methods@#More sophisticated suicide prevention approaches according to age, sex, and occupation have been proposed, demanding for a more detailed revision of “Suicide CARE.” Thus, during the period from August 2019 to February 2020, “Suicide CARE” has been updated to version 2.0. The assessments on domestic gatekeeper training programs for suicide prevention, international gatekeeper training programs for suicide prevention, psychological autopsy interview reports between 2015 and 2018, and the evaluation of feedback from people who completed “Suicide CARE” version 1.6 training were performed. @*Results@#We describe the revision process of “Suicide CARE,” revealing that “Suicide CARE” version 2.0 has been developed using an evidence-based methodology. @*Conclusion@#It is expected that “Suicide CARE” version 2.0 be positioned as the basic framework for many developing gatekeeper training programs for suicide prevention in Korea in the near future.

Contents of the Standardized Suicide Prevention Program for Gatekeeper Intervention in Korea, Version 2.0

Objective@#Suicide is a huge nationwide problem that incurs a lot of socio-economic costs. Suicide also inflicts severe distress on the people left behind. The government of the Republic of Korea has been making many policy efforts to reduce suicide rate. The gatekeeper program, ‘Suicide CARE’, is one of the meaningful modalities for preventing suicide. @*Methods@#Multidisciplinary research team collaborated to update the ‘Suicide CARE’ to version 2.0. @*Results@#In the ‘Introductory part’, the authors have the time to think about the necessity and significance of the program before conducting full-scale gatekeeper training. In the ‘Careful observation’ part, trainees learn how to understand and recognize the various linguistic, behavioral, and situational signals that a person shows before committing suicide. In the ‘Active listening’ part, trainees learn how to ask suicide with a value-neutral attitude as well listening empathetically. In the ‘Risk evaluation and Expert referral’ part, trainees learn intervening strategies to identify a person’s suicidal intention, plan, and past suicide attempts, and connect the person to appropriate institutes or services. @*Conclusion@#Subsequent studies should be conducted to verify the efficacy of the gatekeeper program.

Risk factors of 30-day mortality following endovascular thoracic and abdominal aortic repair with general anesthesia

BACKGROUND: Recently, endovascular aortic repair (EVAR) and thoracic endovascular aortic repair (TEVAR), have been used for treatment of thoracic and abdominal aortic aneurysms. The purpose of this study was to analyze the outcome and predictors for 30-day mortality and complications, in patients that underwent EVAR and/or TEVAR under general anesthesia. METHODS: In this study, 151 cases of EVAR and/or TEVAR under general anesthesia in 140 patients during 2009–2017 were studied. The primary outcome was 30-day mortality after surgery. Multivariate logistic regression analysis was used, to clarify risk for postoperative 30-day mortality. RESULTS: Postoperative 30-day mortality rate was 9.9% in the study population (10.3% in EVAR, and 9.3% in TEVAR, respectively). Seventy-two cases (47.7%) experienced postoperative complications within 30 days. Elderly older than age 76.5 (odds ratio [ORs] = 48.89, 95% confidential interval [95% CI] 1.40–1,710.25, P = 0.032), technically expertness (OR = 0.01, 95% CI 0.00–0.40, P = 0.013), severity of systemic complications (OR = 23.24, 95% CI, 2.27–238.24, P = 0.008), and severity of local-vascular complications (OR = 31.87, 95% CI, 1.29–784.66, P = 0.034) were significantly associated with 30-day mortality. CONCLUSIONS: This study revealed that elderly, technically expertness, and severity of systemic and local-vascular complications were associated with 30-day mortality of EVAR and TEVAR in aortic aneurysm.

β-arrestin2 Affects Cardiac Progenitor Cell Survival through Cell Mobility and Tube Formation in Severe Hypoxia

BACKGROUND AND OBJECTIVES: β-arrestin2 (β-arr2) basically regulates multiple signaling pathways in mammalian cells by desensitization and internalization of G-protein coupled receptors (GPCRs). We investigated impacts of β-arr2 on survival, mobility, and tube formation of cardiac progenitor cells (CPCs) obtained from wild-type (WT) mouse (CPC-WT), and β-arr2 knock-out (KO) mouse (CPC-KO) cultured in presence or absence of serum and oxygen as non-canonical roles in GPCR system. METHODS: CPCs were cultured in Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 -based media containing fetal bovine serum and growth factors. Survival of 2 types of CPCs in hypoxia and/or serum deprivation was measured by fluorescence-activated cell sorting. Wound healing ability, and tube formation ability on Matrigel of 2 kinds of CPCs were compared in normoxic and hypoxic cultures. Protein expression related to survival and mobility were measured with the Western blot for each culture conditions. RESULT: CPC-KO showed significantly worse mobility in the wound healing assay and in tube formation on Matrigel especially in hypoxic culture than did the CPC-WT. Also, CPC-KO showed significantly higher apoptosis fraction in both normoxic and hypoxic cultures than did the CPC-WT. Expression of proteins associated with cell survival and mobility, e.g., protein kinase B (Akt), β-catenin, and glycogen synthase kinase-3β (GSK-3β) was significantly worse in CPC-KO. CONCLUSIONS: The CPC-KO had significantly worse cell mobility, tube formation ability, and survival than the CPC-WT, especially in the hypoxic cultures. Apparently, β-arr2 is important on CPC survival by means of mobility and tube formation in myocardial ischemia.

Risk factors for postoperative delirium following total knee arthroplasty in elderly patients

BACKGROUND: Postoperative delirium has been suggested as a significant predictor of postoperative morbidity and mortality in elderly patients. They usually have multiple comorbidities, including cardiovascular, respiratory, renal, and neurologic disease. We aimed to determine the incidence rate and modifiable risk factors of postoperative delirium following total knee arthroplasty in elderly. METHODS: We reviewed the medical records of 318 elderly patients (age >65 years) underwent unilateral total knee arthroplasty between 2009 and 2016. Patient demographics, American Society of Anesthesiologists physical status, preoperative comorbidities, type and duration of anesthesia and surgery, length of hospital stay, ambulation ability, frequency of intraoperative hypotension, frequency of hypothermia, whether the patient was transfused or heparinized, and perioperative laboratory results were evaluated. Univariate and multivariate logistic regression analyses were used to identify significant independent predictors of postoperative delirium. RESULTS: The incidence rate of postoperative delirium was 6% in this study. Univariate analysis showed that postoperative delirium was significantly associated with age, body mass index, general anesthesia, anesthesia time, preoperative dementia, intraoperative hypotension, preoperative hemoglobin, blood transfusion, and intraoperative hypothermia. Preoperative dementia (odds ratio [OR] = 8.80), intraoperative hypotension (OR = 1.06), and preoperative hemoglobin (OR = 0.66) were significant independent risk factors of postoperative delirium. CONCLUSIONS: Preoperative dementia is the most important risk factor of postoperative delirium. High-risk patients undergoing total knee arthroplasty should be thoroughly evaluated and their dementia should be managed preoperatively. Adequate management of preoperative hemoglobin and intraoperative hypotension might also be helpful in reducing the incidence of postoperative delirium in this population.

β-arrestin2 Affects Cardiac Progenitor Cell Survival through Cell Mobility and Tube Formation in Severe Hypoxia

BACKGROUND AND OBJECTIVES@#β-arrestin2 (β-arr2) basically regulates multiple signaling pathways in mammalian cells by desensitization and internalization of G-protein coupled receptors (GPCRs). We investigated impacts of β-arr2 on survival, mobility, and tube formation of cardiac progenitor cells (CPCs) obtained from wild-type (WT) mouse (CPC-WT), and β-arr2 knock-out (KO) mouse (CPC-KO) cultured in presence or absence of serum and oxygen as non-canonical roles in GPCR system.@*METHODS@#CPCs were cultured in Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 -based media containing fetal bovine serum and growth factors. Survival of 2 types of CPCs in hypoxia and/or serum deprivation was measured by fluorescence-activated cell sorting. Wound healing ability, and tube formation ability on Matrigel of 2 kinds of CPCs were compared in normoxic and hypoxic cultures. Protein expression related to survival and mobility were measured with the Western blot for each culture conditions.RESULT: CPC-KO showed significantly worse mobility in the wound healing assay and in tube formation on Matrigel especially in hypoxic culture than did the CPC-WT. Also, CPC-KO showed significantly higher apoptosis fraction in both normoxic and hypoxic cultures than did the CPC-WT. Expression of proteins associated with cell survival and mobility, e.g., protein kinase B (Akt), β-catenin, and glycogen synthase kinase-3β (GSK-3β) was significantly worse in CPC-KO.@*CONCLUSIONS@#The CPC-KO had significantly worse cell mobility, tube formation ability, and survival than the CPC-WT, especially in the hypoxic cultures. Apparently, β-arr2 is important on CPC survival by means of mobility and tube formation in myocardial ischemia.

Time-dependent proteomic and genomic alterations in Toll-like receptor-4-activated human chondrocytes: increased expression of lamin A/C and annexins

Activation of Toll-like receptor-4 (TLR-4) in articular chondrocytes increases the catabolic compartment and leads to matrix degradation during the development of osteoarthritis. In this study, we determined the proteomic and genomic alterations in human chondrocytes during lipopolysaccharide (LPS)-induced inflammation to elucidate the underlying mechanisms and consequences of TLR-4 activation. Human chondrocytes were cultured with LPS for 12, 24, and 36 h to induce TLR-4 activation. The TLR-4-induced inflammatory response was confirmed by real-time PCR analysis of increased interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) expression levels. In TLR-4-activated chondrocytes, proteomic changes were determined by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-mass spectroscopy analysis, and genomic changes were determined by microarray and gene ontology analyses. Proteomics analysis identified 26 proteins with significantly altered expression levels; these proteins were related to the cytoskeleton and oxidative stress responses. Gene ontology analysis indicated that LPS treatment altered specific functional pathways including ‘chemotaxis’, ‘hematopoietic organ development’, ‘positive regulation of cell proliferation’, and ‘regulation of cytokine biosynthetic process’. Nine of the 26 identified proteins displayed the same increased expression patterns in both proteomics and genomics analyses. Western blot analysis confirmed the LPS-induced increases in expression levels of lamin A/C and annexins 4/5/6. In conclusion, this study identified the time-dependent genomic, proteomic, and functional pathway alterations that occur in chondrocytes during LPS-induced TLR-4 activation. These results provide valuable new insights into the underlying mechanisms that control the development and progression of osteoarthritis.

Associations between Body Mass Index and Chronic Atrophic Gastritis and Intestinal Metaplasia / 대한소화기학회지

BACKGROUND/AIMS: Chronic atrophic gastritis (AG) and intestinal metaplasia (IM) of the stomach are premalignant lesions. The present study aimed to examine the associations between obesity and these lesions. METHODS: A total of 2,997 patients, who underwent gastroscopy, participated in this study, excluding those who had been diagnosed with gastric cancer. Participants were divided into four groups based on their body mass index (BMI). The risk of AG and IM with increasing BMI was analyzed in men and women, separately. RESULTS: The association between BMI and AG was not significant. After adjusting for age, smoking, alcohol, and AG, the odds ratios for IM in the overweight, obesity, and severe obesity groups were 2.25 (95% confidence interval [CI], 1.50-3.37), 2.32 (95% CI, 1.58-3.42), and 4.86 (95% CI, 2.04-11.5) in men, and 2.66 (95% CI, 1.29-5.47), 4.46 (95% CI, 2.28-8.75), and 9.57 (95% CI, 3.26-28.12) in women, compared with the normal BMI group. CONCLUSIONS: Gastric IM was significantly associated with increased BMI.

NecroX-5 protects mitochondrial oxidative phosphorylation capacity and preserves PGC1alpha expression levels during hypoxia/reoxygenation injury

Although the antioxidant and cardioprotective effects of NecroX-5 on various in vitro and in vivo models have been demonstrated, the action of this compound on the mitochondrial oxidative phosphorylation system remains unclear. Here we verify the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity during hypoxia-reoxygenation (HR). Necrox-5 treatment (10 microM) and non-treatment were employed on isolated rat hearts during hypoxia/reoxygenation treatment using an ex vivo Langendorff system. Proteomic analysis was performed using liquid chromatography-mass spectrometry (LC-MS) and non-labeling peptide count protein quantification. Real-time PCR, western blot, citrate synthases and mitochondrial complex activity assays were then performed to assess heart function. Treatment with NecroX-5 during hypoxia significantly preserved electron transport chain proteins involved in oxidative phosphorylation and metabolic functions. NecroX-5 also improved mitochondrial complex I, II, and V function. Additionally, markedly higher peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1alpha) expression levels were observed in NecroX-5-treated rat hearts. These novel results provide convincing evidence for the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity and in preserving PGC1alpha during cardiac HR injuries.

Mitochondrial calcium uniporter inhibition attenuates mouse bone marrow-derived mast cell degranulation induced by beta-1,3-glucan

Mast cells are primary mediators of allergic inflammation. Beta-1,3-glucan (BG) protects against infection and shock by activating immune cells. Activation of the BG receptor induces an increase in intracellular Ca2+, which may induce exocytosis. However, little is known about the precise mechanisms underlying BG activation of immune cells and the possible role of mitochondria in this process. The present study examined whether BG induced mast cell degranulation, and evaluated the role of calcium transients during mast cell activation. Our investigation focused on the role of the mitochondrial calcium uniporter (MCU) in BG-induced degranulation. Black mouse (C57) bone marrow-derived mast cells were stimulated with 0.5 microg/ml BG, 100 microg/ml peptidoglycan (PGN), or 10 microM A23187 (calcium ionophore), and dynamic changes in cytosolic and mitochondrial calcium and membrane potential were monitored. BG-induced mast cell degranulation occurred in a time-dependent manner, and was significantly reduced under calcium-free conditions. Ruthenium red, a mitochondrial Ca2+ uniporter blocker, significantly reduced mast cell degranulation induced by BG, PGN, and A23187. These results suggest that the mitochondrial Ca2+ uniporter has an important regulatory role in BG-induced mast cell degranulation.

Voluntary stand-up physical activity enhances endurance exercise capacity in rats

Involuntary physical activity induced by the avoidance of electrical shock leads to improved endurance exercise capacity in animals. However, it remains unknown whether voluntary stand-up physical activity (SPA) without forced simulating factors improves endurance exercise capacity in animals. We examined the eff ects of SPA on body weight, cardiac function, and endurance exercise capacity for 12 weeks. Twelve male Sprague-Dawley rats (aged 8 weeks, n=6 per group) were randomly assigned to a control group (CON) or a voluntary SPA group. The rats were induced to perform voluntary SPA (lifting a load equal to their body weight), while the food height (18.0 cm) in cages was increased progressively by 3.5 every 4 weeks until it reached 28.5 cm for 12 weeks. The SPA group showed a lower body weight compared to the CON group, but voluntary SPA did not affect the skeletal muscle and heart weights, food intake, and echocardiography results. Although the SPA group showed higher grip strength, running time, and distance compared to the CON group, the level of irisin, corticosterone, genetic expression of mitochondrial biogenesis, and nuclei numbers were not affected. These findings show that voluntary SPA without any forced stimuli in rats can eff ectively reduce body weight and enhance endurance exercise capacity, suggesting that it may be an important alternative strategy to enhance endurance exercise capacity.

NecroX-5 exerts anti-inflammatory and anti-fibrotic effects via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway in hypoxia/reoxygenation-treated rat hearts

Inflammatory and fibrotic responses are accelerated during the reperfusion period, and excessive fibrosis and inflammation contribute to cardiac malfunction. NecroX compounds have been shown to protect the liver and heart from ischemia-reperfusion injury. The aim of this study was to further define the role and mechanism of action of NecroX-5 in regulating infl ammation and fi brosis responses in a model of hypoxia/reoxygenation (HR). We utilized HR-treated rat hearts and lipopolysaccharide (LPS)-treated H9C2 culture cells in the presence or absence of NecroX-5 (10 µmol/L) treatment as experimental models. Addition of NecroX-5 signifi cantly increased decorin (Dcn) expression levels in HR-treated hearts. In contrast, expression of transforming growth factor beta 1 (TGFβ1) and Smad2 phosphorylation (pSmad2) was strongly attenuated in NecroX-5-treated hearts. In addition, signifi cantly increased production of tumor necrosis factor alpha (TNFα), TGFβ1, and pSmad2, and markedly decreased Dcn expression levels, were observed in LPS-stimulated H9C2 cells. Interestingly, NecroX-5 supplementation effectively attenuated the increased expression levels of TNFα, TGFβ1, and pSmad2, as well as the decreased expression of Dcn. Thus, our data demonstrate potential antiinflammatory and anti-fibrotic effects of NecroX-5 against cardiac HR injuries via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway.

Post-Translational Modifications of Cardiac Mitochondrial Proteins in Cardiovascular Disease: Not Lost in Translation

Protein post-translational modifications (PTMs) are crucial in regulating cellular biology by playing key roles in processes such as the rapid on and off switching of signaling network and the regulation of enzymatic activities without affecting gene expressions. PTMs lead to conformational changes in the tertiary structure of protein and resultant regulation of protein function such as activation, inhibition, or signaling roles. PTMs such as phosphorylation, acetylation, and S-nitrosylation of specific sites in proteins have key roles in regulation of mitochondrial functions, thereby contributing to the progression to heart failure. Despite the extensive study of PTMs in mitochondrial proteins much remains unclear. Further research is yet to be undertaken to elucidate how changes in the proteins may lead to cardiovascular and metabolic disease progression in particular. We aimed to summarize the various types of PTMs that occur in mitochondrial proteins, which might be associated with heart failure. This study will increase the understanding of cardiovascular diseases through PTM.

Rescue of Heart Failure by Mitochondrial Recovery / 대한배뇨장애요실금학회지

Heart failure (HF) is a multifactorial disease brought about by numerous, and oftentimes complex, etiological mechanisms. Although well studied, HF continues to affect millions of people worldwide and current treatments can only prevent further progression of HF. Mitochondria undoubtedly play an important role in the progression of HF, and numerous studies have highlighted mitochondrial components that contribute to HF. This review presents an overview of the role of mitochondrial biogenesis, mitochondrial oxidative stress, and mitochondrial permeability transition pore in HF, discusses ongoing studies that attempt to address the disease through mitochondrial targeting, and provides an insight on how these studies can affect future research on HF treatment.

Mitochondrial pyruvate dehydrogenase phosphatase 1 regulates the early differentiation of cardiomyocytes from mouse embryonic stem cells

Mitochondria are crucial for maintaining the properties of embryonic stem cells (ESCs) and for regulating their subsequent differentiation into diverse cell lineages, including cardiomyocytes. However, mitochondrial regulators that manage the rate of differentiation or cell fate have been rarely identified. This study aimed to determine the potential mitochondrial factor that controls the differentiation of ESCs into cardiac myocytes. We induced cardiomyocyte differentiation from mouse ESCs (mESCs) and performed microarray assays to assess messenger RNA (mRNA) expression changes at differentiation day 8 (D8) compared with undifferentiated mESCs (D0). Among the differentially expressed genes, Pdp1 expression was significantly decreased (27-fold) on D8 compared to D0, which was accompanied by suppressed mitochondrial indices, including ATP levels, membrane potential, ROS and mitochondrial Ca²⁺. Notably, Pdp1 overexpression significantly enhanced the mitochondrial indices and pyruvate dehydrogenase activity and reduced the expression of cardiac differentiation marker mRNA and the cardiac differentiation rate compared to a mock control. In confirmation of this, a knockdown of the Pdp1 gene promoted the expression of cardiac differentiation marker mRNA and the cardiac differentiation rate. In conclusion, our results suggest that mitochondrial PDP1 is a potential regulator that controls cardiac differentiation at an early differentiation stage in ESCs.

The Critical Roles of Zinc: Beyond Impact on Myocardial Signaling

Zinc has been considered as a vital constituent of proteins, including enzymes. Mobile reactive zinc (Zn2+) is the key form of zinc involved in signal transductions, which are mainly driven by its binding to proteins or the release of zinc from proteins, possibly via a redox switch. There has been growing evidence of zinc's critical role in cell signaling, due to its flexible coordination geometry and rapid shifts in protein conformation to perform biological reactions. The importance and complexity of Zn2+ activity has been presumed to parallel the degree of calcium's participation in cellular processes. Whole body and cellular Zn2+ levels are largely regulated by metallothioneins (MTs), Zn2+ importers (ZIPs), and Zn2+ transporters (ZnTs). Numerous proteins involved in signaling pathways, mitochondrial metabolism, and ion channels that play a pivotal role in controlling cardiac contractility are common targets of Zn2+. However, these regulatory actions of Zn2+ are not limited to the function of the heart, but also extend to numerous other organ systems, such as the central nervous system, immune system, cardiovascular tissue, and secretory glands, such as the pancreas, prostate, and mammary glands. In this review, the regulation of cellular Zn2+ levels, Zn2+-mediated signal transduction, impacts of Zn2+ on ion channels and mitochondrial metabolism, and finally, the implications of Zn2+ in health and disease development were outlined to help widen the current understanding of the versatile and complex roles of Zn2+.

Ursolic Acid-Induced Elevation of Serum Irisin Augments Muscle Strength During Resistance Training in Men

Ursolic acid (UA), a type of pentacyclic triterpenoid carboxylic acid purified from natural plants, can promote skeletal muscle development. We measured the effect of resistance training (RT) with/without UA on skeletal muscle development and related factors in men. Sixteen healthy male participants (age, 29.37+/-5.14 years; body mass index=27.13+/-2.16 kg/m2) were randomly assigned to RT (n=7) or RT with UA (RT+UA, n=9) groups. Both groups completed 8 weeks of intervention consisting of 5 sets of 26 exercises, with 10~15 repetitions at 60~80% of 1 repetition maximum and a 60~90-s rest interval between sets, performed 6 times/week. UA or placebo was orally ingested as 1 capsule 3 times/day for 8 weeks. The following factors were measured pre-and post-intervention: body composition, insulin, insulin-like growth factor-1 (IGF-1), irisin, and skeletal muscle strength. Body fat percentage was significantly decreased (p<0.001) in the RT+UA group, despite body weight, body mass index, lean body mass, glucose, and insulin levels remaining unchanged. IGF-1 and irisin were significantly increased compared with baseline levels in the RT+UA group (p<0.05). Maximal right and left extension (p<0.01), right flexion (p<0.05), and left flexion (p<0.001) were significantly increased compared with baseline levels in the RT+UA group. These findings suggest that UA-induced elevation of serum irisin may be useful as an agent for the enhancement of skeletal muscle strength during RT.

Corrigendum to: Ursolic Acid-Induced Elevation of Serum Irisin Augments Muscle Strength During Resistance Training in Men

The original version of this article contained misspelled name of author. The name of Figueroa Arturo is replaced with Arturo Figueroa.

Effects of aged garlic extract and endurance exercise on skeletal muscle FNDC-5 and circulating irisin in high-fat-diet rat models

BACKGROUND/OBJECTIVES: Irisin, a newly identified hormone, is associated with energy homeostasis. We investigated whether aged garlic extract (AGE) and exercise training intervention could improve body weight, insulin sensitivity, skeletal muscle fibronectin domain containing protein 5 (FNDC-5) levels, and plasma irisin in high-fat diet (HFD). MATERIALS/METHODS: Male Sprague Dawley rats were fed a ND (normal diet, n = 5) or HFD (n = 28) for 6 weeks. After 6 weeks, all rats were divided into 5 groups for the next 4 weeks: ND, (normal diet, n = 5), HFD (high-fat diet, n = 7), HFDA (high-fat diet + aged garlic extract, n = 7), HFDE (high-fat diet + exercise, n = 7), and HFDEA (high-fat diet + exercise + aged garlic extract, n = 7). Exercise groups performed treadmill exercises for 15-60 min, 5 days/week, and AGE groups received AGE (2.86 g/kg, orally injected) for 4 weeks. RESULTS: Significant decreases in body weight were observed in the ND, HFDE, and HFDEA groups, as compared with the HFD group. Neither intervention affected the masses of the gastrocnemius muscle or liver. There were no significant differences in glucose levels across the groups. The homeostatic model assessments of insulin resistance were significantly higher in the HFD group, as compared with the ND, HFDA, HFDE, and HFDEA groups. However, skeletal muscle FNDC-5 levels and plasma irisin concentrations were unaffected by AGE or exercise in obese rats. AGE supplementation and exercise training did not affect skeletal muscle FNDC-5 or plasma irisin, which are associated with insulin sensitivity in obese rats. CONCLUSION: Our results suggest that the protection against HFD-induced increases in body fat/weight and insulin resistance that are provided by AGE supplementation and exercise training may not be mediated by the regulation of FNDC-5 or irisin.