The ventromedial nucleus of the hypothalamus (VMH) is a critical component of the forebrain pathways that regulate energy homeostasis. It also plays an important role in the metabolic response to fasting. However, the mechanisms contributing to these physiological processes remain elusive.  https://www.selleckchem.com/products/Sunitinib-Malate-(Sutent).html  Autophagy is an evolutionarily conserved mechanism that maintains cellular homeostasis by turning over cellular components and providing nutrients to the cells during starvation. Here, we investigated the importance of the autophagy-related gene Atg7 in Sf1-expressing neurons of the VMH in control and fasted conditions.
 
  We generated Sf1-Cre; Atg7
  mice and examined their metabolic and cellular response to fasting.
 
  Fasting induces autophagy in the VMH, and mice lacking Atg7 in Sf1-expressing neurons display altered leptin sensitivity and impaired energy expenditure regulation in response to fasting. Moreover, loss of Atg7 in Sf1 neurons causes alterations in the central response to fasting. Furthermore, alterations in mitochondria morphology and activity are observed in mutant mice.
 
  Together, these data show that autophagy is nutritionally regulated in VMH neurons and that VMH autophagy participates in the control of energy homeostasis during fasting.
 Together, these data show that autophagy is nutritionally regulated in VMH neurons and that VMH autophagy participates in the control of energy homeostasis during fasting.In our previous study, the mutation c.2645A > C (p. E882A) was found in the A-Kinase Anchoring Protein 2 (AKAP2) gene, which plays an important role in regulating the development of the skeletal system; however, the specific effect of AKAP2 on chondrocyte proliferation and differentiation and the potential mechanism are still not clear. In the present study, we investigated the effect of AKAP2 in vitro. We successfully isolated human growth plate chondrocytes (GPCs) from growth plate cartilage tissues and identified GPCs by aggrecan expression and flow cytometric analysis. AKAP2 overexpression significantly promoted GPC proliferation, enhanced GPC differentiation, and promoted extracellular matrix (ECM) synthesis, whereas AKAP2 silencing exerted the opposite effects on GPCs. AKAP2 overexpression increased, while AKAP2 silencing decreased, the protein levels of p-extracellular regulated protein kinases (ERK)1/2. More importantly, the promotive effects of AKAP2 overexpression on GPC proliferation, differentiation, and ECM synthesis were significantly reversed by the ERK1/2 signaling antagonist U0126, suggesting that AKAP2 enhances GPC functions through ERK1/2 signaling. In conclusion, we demonstrate AKAP2 overexpression-induced enhancement of GPC functions through ERK1/2 signaling. Considering the critical role of GPC functions in adolescent idiopathic scoliosis (AIS) pathogenesis, the application of AKAP2 targeting in AIS treatment should be investigated in future studies.
  With emerging basic research evidence suggesting that fibroblast growth factor (FGF) 21 is a catabolic molecule on muscle metabolism, we aimed to analyze the serum FGF21 level in relation to sarcopenia in older adults.
 
  Blood samples were collected from 125 participants who underwent evaluation for muscle mass and function in an outpatient geriatric clinic of a teaching hospital. Sarcopenia and related components were determined using cutoff values for the Asian population. The serum FGF21 level was measured using enzyme linked immunosorbent assay.
 
  After controlling for age, sex, and body mass index (BMI), participants with sarcopenia, low muscle mass, and weak muscle strength had 2.3-, 2.0-, and 1.5-fold higher serum FGF21 levels than controls, respectively (p=.033 to <0.001). The serum FGF21 level was positively correlated with sarcopenia phenotype score and inversely correlated with skeletal muscle mass index and grip strength by both crude and multivariate analysis adjusting potential confounders (p=.017 to <0.001). Consistently, higher serum FGF21 level was significantly associated with increased odds for sarcopenia, low muscle mass, and low muscle strength after adjusting for age, sex, and BMI (odds ratio, 1.53-2.61; p=.048 to <0.001).
 
  Higher circulating FGF21 was associated with the likelihood of sarcopenia, lower muscle mass, and worse grip strength in older adults, supporting a potential catabolic role of FGF21 on human muscle health.
 Higher circulating FGF21 was associated with the likelihood of sarcopenia, lower muscle mass, and worse grip strength in older adults, supporting a potential catabolic role of FGF21 on human muscle health.
  Bone mineral density (BMD) assessments alone might not be sufficient for assessing fracture risk in the whole population, and decreased balance is an important risk factor for fracture. The aim of this study was to evaluate the association between baseline physical performance and fracture risk.
 
  This community-based cohort study was conducted in rural areas. The follow-up examination was performed in 4015 subjects for approximately 4years. We used the one-leg standing time (OLST) to assess static balance and the timed up-and-go test (TUGT) to assess dynamic balance. Fractures were assessed during the medical interview.
 
  The participants were divided into quartile groups according to their performance level, and the lowest baseline OLST performance was associated with a 2.1-fold increased risk of major osteoporotic fracture (MOF) independent of age, gender, hip BMD, fall incidence, and lifestyle factors. The participants in the low performance quartile of baseline OLST or TUGT performance had an increased incidence of osteoporosis and falling compared to that in the participants in the highest baseline performance quartile after adjusting for covariates. Among the participants with a femoral neck T-score above -2.5, the participants with an OLST below 14s had a 1.7-fold higher risk of MOF than the participants with an OLST of 14s or more.
 
  The measurement of static balance by the OLST predicted the risk of fracture in Korean adults independent of BMD and fall history. Our results suggest that the OLST may have clinical utility in identifying individuals at risk of fracture, especially those who might not be adequately identified by BMD measurements alone.
 The measurement of static balance by the OLST predicted the risk of fracture in Korean adults independent of BMD and fall history. Our results suggest that the OLST may have clinical utility in identifying individuals at risk of fracture, especially those who might not be adequately identified by BMD measurements alone.