Cardiometabolic Disease Risk in Normal Weight Obesity and Exercise Interventions for Proactive Prevention

PURPOSE Normal weight obesity (NWO) is characterized by a normal body mass index but a high body fat mass percentage and low skeletal muscle mass, thereby increasing the risk of cardiometabolic dysfunction and morbidity. However, the effects of exercise intervention in reducing the risk of cardiometabolic disease in NWO have not been fully elucidated. Therefore, this review aimed to summarize the potential cardiometabolic disease risk and to provide implications of exercise interventions for the proactive prevention of cardiometabolic disease risk in NWO. METHODS We searched and summarized the literature on the cardiometabolic risk factors in NWO. In addition, we summarized literature investigating the effects of exercise intervention on the cardiometabolic risk factors in NWO. We performed the literature search using PubMed, Web of Science, and Google Scholar databases. RESULTS NWO was associated with increased visceral fat, ectopic fat, oxidative stress, inflammatory cytokines, insulin resistance, dyslipidemia, and subclinical atherosclerosis compared with normal weight lean. NWO requires exercise interventions that induce alterations in body composition, such as decreased body fat percentage and increased muscle mass. Resistance exercise (RE) and high-intensity interval exercise (HIIE) can improve lipid components and alter body composition in NWO. In addition, low-intensity blood flow restriction resistance exercise (BFR-RE) may enhance muscular strength and anaerobic power in NWO. CONCLUSIONS The cardiometabolic disease risk is increased in NWO. We suggest that exercise interventions (RE, HIIE, and BFR-RE) may effectively prevent cardiometabolic disease risk and alter body composition in NWO. As this has potential implications for exercise interventions in NWO, further investigations are needed to find the optimal exercise for proactive prevention of cardiometabolic risk in NWO

Detection of EGFR Mutations Using Bronchial Washing-Derived Extracellular Vesicles in Patients with Non-Small-Cell Lung Carcinoma

The detection of epidermal growth factor receptor (EGFR) mutation, based on tissue biopsy samples, provides a valuable guideline for the prognosis and precision medicine in patients with lung cancer. In this study, we aimed to examine minimally invasive bronchial washing (BW)-derived extracellular vesicles (EVs) for EGFR mutation analysis in patients with lung cancer. A lab-on-a-disc equipped with a filter with 20-nm pore diameter, Exo-Disc, was used to enrich EVs in BW samples. The overall detection sensitivity of EGFR mutations in 55 BW-derived samples was 89.7% and 31.0% for EV-derived DNA (EV-DNA) and EV-excluded cell free-DNA (EV-X-cfDNA), respectively, with 100% specificity. The detection rate of T790M in 13 matched samples was 61.5%, 10.0%, and 30.8% from BW-derived EV-DNA, plasma-derived cfDNA, and tissue samples, respectively. The acquisition of T790M resistance mutation was detected earlier in BW-derived EVs than plasma or tissue samples. The longitudinal analysis of BW-derived EVs showed excellent correlation with the disease progression measured by CT images. The EGFR mutations can be readily detected in BW-derived EVs, which demonstrates their clinical potential as a liquid-biopsy sample that may aid precise management, including assessment of the treatment response and drug resistance in patients with lung cancer

A pathogen-derived metabolite induces microglial activation via odorant receptors

Microglia (MG), the principal neuroimmune sentinels in the brain, continuously sense changes in their environment and respond to invading pathogens, toxins, and cellular debris, thereby affecting neuroinflammation. Microbial pathogens produce small metabolites that influence neuroinflammation, but the molecular mechanisms that determine whether pathogen-derived small metabolites affect microglial activation of neuroinflammation remain to be elucidated. We hypothesized that odorant receptors (ORs), the largest subfamily of G protein-coupled receptors, are involved in microglial activation by pathogen-derived small metabolites. We found that MG express high levels of two mouse ORs, Olfr110 and Olfr111, which recognize a pathogenic metabolite, 2-pentylfuran, secreted by Streptococcus pneumoniae. These interactions activate MG to engage in chemotaxis, cytokine production, phagocytosis, and reactive oxygen species generation. These effects were mediated through the G(alpha s)-cyclic adenosine monophosphate-protein kinase A-extracellular signal-regulated kinase and G(beta gamma)-phospholipase C-Ca2+ pathways. Taken together, our results reveal a novel interplay between the pathogen-derived metabolite and ORs, which has major implications for our understanding of microglial activation by pathogen recognition. Database Model data are available in the PMDB database under the accession number PM0082389.N

Acute effect of exercise intensity on circulating FGF-21, FSTL-1, cathepsin B, and BDNF in young men

Background/objectives: Exercise intensity is potentially an important regulator of various exerkines secretion, but the optimal exercise intensity to increase and sustain exerkines levels, including FGF-21, FSTL-1, cathepsin B, and BDNF in humans, has not yet been fully elucidated. This study aimed to examine the circulating levels of FGF-21, FSTL-1, cathepsin B, and BDNF according to the exercise intensity. Methods: Nine young men (24.0 ± 0.4 years old) performed 4 different experimental sessions at 1-week intervals: 1) a control session (CTRL; no exercise); 2) moderate-intensity continuous exercise (MICE, 55% HRR); 3) vigorous-intensity continuous exercise (VICE, 85% HRR); and 4) high-intensity interval exercise (HIIE, 4 repetitions of a 30-s of “all out” cycling workout followed by a 4-min recovery). Blood samples were collected at 4 different time points (pre-exercise, immediately post-exercise, 30 min post-exercise, and 90 min post-exercise). Results: Serum FGF-21, FSTL-1, cathepsin B, and BDNF were higher in HIIE than in CTRL immediately post-exercise, and FSTL-1, cathepsin B, and BDNF were higher in HIIE than in MICE immediately post-exercise (P < 0.05). The AUC for FGF-21, FSTL-1, and BDNF was higher in HIIE than in CTRL, and the AUC for FGF-21 and BDNF was higher in HIIE than in MICE (P < 0.05). Furthermore, the change in blood lactate was positively correlated with the changes in all exerkines. Conclusions: This study demonstrates that acute HIIE effectively increases serum FGF-21, FSTL-1, cathepsin B, and BDNF compared to MICE. Therefore, the secretion of exerkines, including FGF-21, FSTL-1, cathepsin B, and BDNF may be exercise intensity-dependent

Odorant receptors in cancer

Odorant receptors (ORs), the largest subfamily of G protein-coupled receptors, detect odorants in the nose. In addition, ORs were recently shown to be expressed in many nonolfactory tissues and cells, indicating that these receptors have physiological and pathophysiological roles beyond olfaction. Many ORs are expressed by tumor cells and tissues, suggesting that they may be associated with cancer progression or may be cancer biomarkers. This review describes OR expression in various types of cancer and the association of these receptors with various types of signaling mechanisms. In addition, the clinical relevance and significance of the levels of OR expression were evaluated. Namely, levels of OR expression in cancer were analyzed based on RNA-sequencing data reported in the Cancer Genome Atlas; OR expression patterns were visualized using t-distributed stochastic neighbor embedding (t-SNE); and the associations between patient survival and levels of OR expression were analyzed. These analyses of the relationships between patient survival and expression patterns obtained from an open mRNA database in cancer patients indicate that ORs may be cancer biomarkers and therapeutic targets. [BMB Reports 2022; 55(2): 72-80] © 2022 by the The Korean Society for Biochemistry and Molecular BiologyTRU