Salivary Cortisol and Melatonin, Sleep, and Behavioral Patterns in Older Adults Living With Dementia.

BACKGROUND: Over half of the older adults living with dementia have behavioral and psychological symptoms of dementia (BPSD), including sleep disturbance; however, little is known about physiological markers. Salivary cortisol and melatonin have been identified as potential biomarkers of BPSD, with evidence suggesting a relationship between these biomarkers and various behavioral factors, as well as sleep and activity patterns. OBJECTIVES: The aim of this study was to investigate the time-dependent changes in salivary cortisol and melatonin levels in older adults with dementia, their relationship with the sleep-wake cycle, and their correlation with BPSD symptoms and behavioral factors. METHODS: This observational study conducted in Seoul and Gyeonggi-do, South Korea, used data from 172 older adults with dementia, measuring sleep and activity patterns for 2 weeks using a wearable device, in addition to administering questionnaires for neuropsychiatric and psychological symptoms-the Neuropsychiatric Inventory, Cohen-Mansfield Agitation Inventory, and Cornell Scale for Depression in Dementia. Salivary cortisol and melatonin levels were measured at four time points and divided into four groups based on a dual-trajectory model. Differences among the groups were analyzed using one-way analysis of variance. RESULTS: The participants showed normal but heterogeneous patterns of salivary cortisol and melatonin levels. Dual-trajectory pattern analysis showed that higher levels of melatonin during the daytime were correlated with poor nighttime sleep efficiency and decreased disinhibited behaviors, and higher levels of cortisol at all four time points were associated with decreased physical activity. DISCUSSION: Measuring and analyzing periodic changes in cortisol and melatonin levels can predict various behavioral symptoms (e.g., sleep disturbances, activity counts, and disinhibition) in older adults with dementia. A study with an experimental design is needed to discover the direct physiological interactions between cortisol, melatonin, and these symptoms.

Comprehensive lifestyle modification interventions for metabolic syndrome: A systematic review and meta-analysis.

INTRODUCTION: Previous systematic reviews and meta-analyses have mainly focused on improvements in the number of metabolic syndrome risk factors and individual changes in each risk factor, making it challenging to examine the impact of comprehensive lifestyle modification interventions on adherence to recommended health behaviors. To address this gap, we conducted a systematic and meta-analysis aimed at identifying clinical parameter levels associated with lifestyle modification outcomes and adherence to recommended health behaviors for individuals with metabolic syndrome. METHODS: A total of seven studies retrieved from four databases (CINAHL, Medline via PubMed, American Psychological Association PsycINFO, and Embase) were included in the review. The selected studies, which demonstrated improvements in health behaviors, all included diet and exercise as main factors of comprehensive lifestyle modification in home settings. RESULTS: Our findings suggest that a 6-month comprehensive intervention including diet and exercise can be effective in decreasing glucose levels and systolic blood pressure. However, given the limited available data, further studies investigating the efficacy of interventions of varying durations are needed. DISCUSSION: Although our review included a small number of studies, comprehensive lifestyle modifications consisting of at least two components (primarily diet and exercise) can improve health behaviors and some clinical parameters among individuals with metabolic syndrome. Future studies are needed to investigate the long-term effects of lifestyle modifications on health behavior adherence and explore effective interventions to address certain clinical parameters, such as high-density lipoprotein levels. Also, we recommend using objective and quantifiable measure to compare adherence to recommended lifestyle modifications across studies. CLINICAL RELEVANCE: This research provides empirical evidence of the effectiveness of comprehensive lifestyle modification and emphasizes the need to develop long-term nursing strategies in public health that can be used to effectively manage metabolic syndrome.

Feasibility and efficacy of TouchCare system using application for older adults living alone: a pilot pre-experimental study.

BACKGROUND: With the number of older people living alone continuously rising, health-monitoring systems using information and communication technology (ICT) have been developed to manage their health issues. Life logging and human body communication sensor, types of ICT, have been adapted to manage and monitor health status of the elderly. However, its feasibility and efficacy remain unclear. This study aimed to examine the feasibility of TouchCare system which combined life logging with human body communication technology and its effect on the physical and psychological status of older adults living alone. METHODS: The TouchCare system, which consisted of a wearable watch, touchpad sensors, TouchCare application, and context-aware artificial intelligence, was developed by DNX Co. Ltd and used by the participants for 5 months. Out of the 111 selected participants, 91 replied to the satisfaction survey, and 22 participated in further investigation regarding their physical and psychological status. Finally, health assessment from 14 participants and sensor data from 13 participants (mean age = 77.4; SD = 3.8) were analyzed to compare their health status and health-related behaviors before and after use of the system. RESULTS: Out of the 91 participants who took the survey, 51.6% were satisfied with the system. Nutritional status (pre-intervention (10.6 ± 2.0) vs. post-intervention (11.8 ± 1.9), P = 0.04) and fall efficacy (pre-intervention (89.2 ± 15.3) vs. post-intervention (99.9 ± 0.5), P = 0.001) significantly improved after use of the system. Chronic pain (pre-intervention (4.8 ± 2.5) vs. post-intervention (4.4 ± 3.7), P = 0.78) and depressive symptoms (pre-intervention (5.7 ± 3.9) vs. post-intervention (5.4 ± 3.1), P = 0.60) reduced, while cognitive function (pre-intervention (4.1 ± 1.4) vs. post-intervention (4.6 ± 1.1), P = 0.15) and physical performance related to walking improved (pre-intervention (3.9 ± 0.2) vs. post-intervention (4.0 ± 0), P = 0.35), but were not significant. Behaviors related to physical activity and gait improved after use of the system; touch counts of refrigerator and microwave also increased with a decrease in night touch counts. CONCLUSIONS: The TouchCare system was acceptable to older people living alone, and it efficiently managed their daily living while promoting their health-related behaviors. Further experimental studies are required to verify the effectiveness of the system, and to develop the system which meet the individualized needs of older people living alone.

Non-pharmacological interventions using information and communication technology for behavioral and psychological symptoms of dementia: A systematic review and meta-analysis protocol.

AIM: To review and examine the effectiveness of non-pharmacological interventions on behavioural and psychological symptoms of dementia using information and communication technology. DESIGN: This is a systematic review and meta-analysis. METHODS: The databases including PubMed, CINAHL with Full Text (EBSCOhost), PsycINFO, Embase, and the Cochrane Library will be searched for all published studies. Studies will be screened and selected with criteria described in PICOS format. Risk of bias will be assessed by the National Institute for Health and Clinical Excellence checklist. Data will be extracted from eligible studies and used to perform a meta-analysis examining the overall effects and effects on individual outcomes. Additionally, we will conduct meta-regression to examine the association between explanatory variables and behavioural and psychological symptoms. This study has been funded since June 2020. DISCUSSION: This study will be the first to reveal the effects of non-pharmacological interventions using information and communication technology on behavioural and psychological symptoms of dementia. Furthermore, this study will provide updated and valid evidence of interventions using this for managing behavioural and psychological symptoms of dementia. IMPACT: Although non-pharmacological interventions using information and communication technology for older adults living with dementia are continuously developing, their direct effect remains unclear. This study will evaluate the effectiveness of these interventions on behavioural and psychological symptoms of dementia and provide the evidence to implement these interventions among older adults living with dementia. Thus, caregivers and nursing staff can manage behavioural and psychological symptoms of dementia more effectively by incorporating information and communication technology.

Monoacylglycerol O-acyltransferase 1 is regulated by peroxisome proliferator-activated receptor γ in human hepatocytes and increases lipid accumulation.

Monoacylglycerol O-acyltransferase (MGAT) is an enzyme that is involved in triglyceride synthesis by catalyzing the formation of diacylglycerol from monoacylglycerol and fatty acyl CoAs. Recently, we reported that MGAT1 has a critical role in hepatic TG accumulation and that its suppression ameliorates hepatic steatosis in a mouse model. However, the function of MGAT enzymes in hepatic lipid accumulation has not been investigated in humans. Unlike in rodents, MGAT3 as well as MGAT1 and MGAT2 are present in humans. In this study, we evaluated the differences between MGAT subtypes and their association with peroxisome proliferator-activated receptor γ (PPARγ), a regulator of mouse MGAT1 expression. In human primary hepatocytes, basal expression of MGAT1 was lower than that of MGAT2 or MGAT3, but was strongly induced by PPARγ overexpression. A luciferase assay as well as an electromobility shift assay revealed that human MGAT1 promoter activity is driven by PPARγ by direct binding to at least two regions of the promoter in 293T and HepG2 cells. Moreover, siRNA-mediated suppression of MGAT1 expression significantly attenuated lipid accumulation by PPARγ overexpression in HepG2 cells, as evidenced by oil-red-O staining. These results suggest that human MGAT1 has an important role in fatty liver formation as a target gene of PPARγ, and blocking MGAT1 activity could be an efficient therapeutic way to reduce nonalcoholic fatty liver diseases in humans.

Predictors of older adults' health behaviours to prevent COVID-19 transmission: a multilevel analysis.

OBJECTIVES: While older adults showed higher mortality during COVID-19 pandemic, protective behaviours (knowledge regarding coping with COVID-19 symptoms and preventive behaviours) were highlighted to be important to prevent the spread of infection. This study aimed to identify individual and community-level variables influencing deficient knowledge regarding coping with COVID-19 and not-practicing COVID-19 of older adults during the pandemic. DESIGN: This is a secondary analysis of a cross-sectional study using the 2020 Korea Community Health Survey (KCHS). SETTING: 255 community public health centres nationwide, South Korea. METHODS AND ANALYSIS: Using 2020 KCHS data, multilevel logistic regression analysis was conducted on 55 005 adults aged 65 years or older. RESULTS: Older adults who reside alone, as opposed to with their spouse and who lack the support of another individual exhibited insufficient COVID-19 coping-related knowledge (OR: 1.142, p<0.001) and poor preventive behaviours (OR: 1.177, p<0.001). Furthermore, lower municipal social welfare budget levels were associated with worse health behaviours (OR: 0.062, p<0.001). Specifically, older adults living in rural areas were less likely to engage in COVID-19 preventive behaviours compared with those in urban areas (OR: 1.247, p<0.001). Additionally, the effectiveness of mass media as a motivating factor for adopting preventive measures was only significant in rural populations (OR: 0.944, p<0.05). CONCLUSIONS: Both individual-level and community-level approaches are necessary as an initial response during the pandemic. Since elderly people living alone with low socioeconomic status are vulnerable groups with poor health behaviours, it is helpful to provide social support on how to respond to infectious diseases and manage symptoms. In addition, it is important to expand the municipal social welfare budget to promote health equity between regions through appropriate health behaviour education and the strengthening of public medical services.

Plasma Myokine Profiles in Patients With AChR- and MuSK-Ab-Positive Myasthenia Gravis.

BACKGROUND AND PURPOSE: Myokines include cytokines secreted by muscle fibers, which are the final targets of myasthenia gravis (MG). This pilot study investigated whether myokine plasma concentrations are altered in patients with MG and assessed the association between the concentration of each myokine and disease severity. METHODS: We compared the plasma concentrations of 15 myokines in 63 patients with acetylcholine receptor antibody (Ab)-positive MG and 14 with muscle-specific tyrosine kinase Ab-positive MG (MuSK MG) with those in 15 healthy controls. Plasma myokine concentrations were measured using a Luminex multiplex assay kit with magnetic beads that contained Abs for 15 myokines. Correlations between myokine concentration and clinical scale results were analyzed. RESULTS: The concentration of fractalkine in plasma was higher in MG (median [interquartile range]=419.6 [38.7-732.5] pg/mL) than in controls (158.5 [0.0-313.2] pg/mL, p=0.034). The leukemia inhibitory factor concentration was also found to be higher in MuSK MG (29.9 [8.7-40.1] pg/mL) than in healthy controls (7.6 [0.0-15.6] pg/mL, p=0.013). Fatty-acid-binding protein 3 (FABP3) concentrations in plasma were positively associated with clinical parameters for MG severity, including scores on the Quantitative Myasthenia Gravis score (p=0.008), Myasthenia Gravis Activities of Daily Living (p=0.003), and Myasthenia Gravis Composite (p=0.024) scales. FABP3 concentration in plasma tended to decrease after treatment in patients without additional relapse but increased in those with further relapse. CONCLUSIONS: The plasma myokine profile was significantly altered in patients with MG. FABP3 concentration may be useful in assessing disease severity and predicting the treatment response.

The effectiveness of non-pharmacological interventions using information and communication technologies for behavioral and psychological symptoms of dementia: A systematic review and meta-analysis.

BACKGROUND: Although behavioral and psychological symptoms of dementia are a global public health challenge, non-pharmacological interventions using information and communication technologies can be an affordable, cost-effective, and innovative solution. OBJECTIVES: This study aimed to examine the effectiveness of non-pharmacological interventions using information and communication technologies on the behavioral and psychological symptoms of dementia and identify potential moderators of intervention effects. DESIGN: Systematic review and meta-analysis of randomized controlled trials. METHODS: A systematic literature review was conducted using PubMed, CINAHL, PsycINFO, Embase, and the Cochrane Library from May 2022. Randomized controlled trials that examined the effects of non-pharmacological interventions using information and communication technologies on the behavioral and psychological symptoms of dementia were included. A meta-analysis using a random-effects model was performed to calculate the pooled standardized mean differences between overall symptoms and each type of symptom. For moderator analyses, subgroup and meta-regression analyses were performed. RESULTS: Sixteen trials (15 articles) met the eligibility criteria. The interventions were grouped into activity engagement interventions using digital health that provided music and reminiscence therapy, physical exercise, social interaction interventions using social robots, and telehealth-based care aid interventions that provided coaching or counseling programs. Pooled evidence demonstrated that non-pharmacological interventions using information and communication technologies exerted a large effect on depression (SMD = -1.088, 95% CI -1.983 to -0.193, p = 0.017), a moderate effect on overall behavioral and psychological symptoms of dementia (SMD = -0.664, 95% CI -0.990 to -0.338, p < 0.001), and agitation (SMD = -0.586, 95% CI -1.130 to -0.042, p = 0.035). No effects on neuropsychiatric symptoms (SMD = -0.251, 95% CI -0.579 to 0.077, p = 0.133), anxiety (SMD = -0.541, 95% CI -1.270 to 0.188, p = 0.146), and apathy (SMD = -0.830, 95% CI -1.835 to 0.176, p = 0.106) were reported. Moderator analyses identified the mean age of the participants as a potential moderator of intervention effects. CONCLUSIONS: Evidence from this systematic review and meta-analysis suggests that non-pharmacological interventions, using information and communication technologies, were an applicable approach to managing behavioral and psychological symptoms among older adults with dementia, with moderate to large effect sizes. However, evidence on anxiety and apathy is inconclusive due to the limited number of existing randomized controlled trials. Future studies with subgroup analyses are warranted to conclude the most effective types of intervention using information and communication technologies for each type of symptom. REGISTRATION: CRD42021258498.

Endrin potentiates early-stage adipogenesis in 3T3-L1 cells by activating the mammalian target of rapamycin.

Obesogens are a type of endocrine-disrupting chemicals (EDCs) that disrupt the human endocrine system, resulting in obesity and metabolic disease. Several obesogens, including bisphenol A, tolylfluanid, and some pesticides, have been identified and studied previously; however, the underlying molecular mechanisms by which obesogens interfere with adipogenesis and induce insulin resistance in adipocyte remain unknown. This study aims to determine which type of chemical is the most potent obesogen and to investigate its effect on adipogenesis-related gene expressions. 3T3-L1, a pre adipocyte cell line, was differentiated into mature adipocytes with either vehicle or various obesogens, including bisphenol A, tolylfluanid, and endrin, as well as corticosterone, at the same dose. Subsequently, intracellular and secreted triglyceride levels were measured, and the expression of genes and proteins involved in adipogenesis and lipogenesis was investigated. We found that endrin was the most potent regulator of adipogenic differentiation, as compared to tolylfluanid, bisphenol A, and corticosterone. Endrin increased intracellular and secreted triglyceride levels and enhanced the expression of adipogenic transcription factors as well as the terminal differentiation marker in a dose-dependent manner. During the early stages of differentiation, endrin enhanced mammalian target of rapamycin (mTOR) activity, which was suppressed by the pharmacological blockade of the protein kinase B-mTOR pathway, with repressed adipogenic differentiation. However, endrin did not change the expression levels of the downstream members of the mTOR signaling pathway or proteins related to lipolysis in response to insulin. Thus, we suggest that endrin potentiates early-stage adipogenic differentiation by activating the mTOR pathway.

Serpina3c Regulates Adipogenesis by Modulating Insulin Growth Factor 1 and Integrin Signaling.

Preadipocyte differentiation can be induced upon a hormonal treatment, and various factors secreted by the cells may contribute to adipogenesis. In this study, RNA-seq revealed Serpina3c as a critical factor regulating the signaling network during adipogenesis. Serpina3c is a secretory protein and is highly expressed in fat tissues. Knockdown of Serpina3c decreased adipogenesis by attenuating the mitotic clonal expansion of 3T3-L1 cells. These cells exhibited decreases in integrin α5, which abolished the phosphorylation of integrin ß3. We found that Serpina3c inhibits a serine protease that regulates integrin α5 degradation. Knockdown of Serpina3c disrupted integrin-mediated insulin growth factor 1 (IGF-1) signaling and ERK activation. Serpina3c-mediated regulation of integrin-IGF-1 signaling is also associated with AKT activation, which affects the nuclear translocation of GSK3ß. Altogether, our results indicate that Serpina3c secreted from differentiating adipocytes inhibits serine proteases to modulate integrin/IGF-1-mediated ERK and AKT signaling and thus is a critical factor contributing to adipogenesis.

Dexras1 plays a pivotal role in maintaining the equilibrium between adipogenesis and osteogenesis.

BACKGROUND: Chronic steroid treatment causes an increase in visceral adiposity and osteoporosis. It is believed that steroids may alter a balance between differentiation of mesenchymal stem cells (MSCs) into either adipocytes or osteoblasts; however, the detailed molecular mechanisms are unclear. We previously identified Dexras1 as a critical factor that potentiates adipogenesis in response to glucocorticoids. Thus, in this study, we investigated the role of Dexras1 in maintaining the balance between chronic steroid treatment-associated adipogenesis and osteoporosis. MATERIAL AND METHODS: We treated wild type (WT) and Dexras1 knockout (KO) mice with dexamethasone for five weeks followed by 60% HFD for additional two weeks with dexamethasone. The changes of glucocorticoid-induced body weight gain and osteoporosis were analyzed. Bone marrow derived stromal cells (BMSCs) and mouse embryonic fibroblasts (MEFs) extracted from WT and Dexras1 KO mice, as well as MC3T3-E1 pre-osteoblasts and osteoclasts differentiated from RAW264.7 were analyzed to further define the role of Dexras1 in osteoblasts and osteoclasts. RESULTS: Dual-energy X-ray absorptiometry and micro-computed tomography analyses in murine femurs revealed that Dexras1 deficiency was associated with increased osteogenesis, concurrent with reduced adipogenesis. Furthermore, Dexras1 deficiency promoted osteogenesis of BMSCs and MEFs in vitro, suggesting that Dexras1 deficiency prevents steroid-induced osteoporosis. We also observed that Dexras1 downregulated SMAD signaling pathways, which reduced the osteogenic differentiation capacity of pre-osteoblast MC3T3-E1 cells into mature osteoblasts. CONCLUSION: We propose that Dexras1 is critical for maintaining the equilibrium between adipogenesis and osteogenesis upon steroid treatment.

SCARA5 plays a critical role in the commitment of mesenchymal stem cells to adipogenesis.

Mesenchymal stem cells have the capacity to give rise to multiple cell types, such as adipocytes, osteoblasts, chondrocytes, and myocytes. However, the molecular events responsible for the lineage specification and differentiation of mesenchymal stem cells remain unclear. Using gene expression profile studies, we determined that Scavenger receptor class A, member 5 (SCARA5) is a novel mediator of adipocyte commitment. SCARA5 was expressed at a higher level in committed A33 preadipocyte cells compared to C3H10T1/2 pluripotent stem cells. Gain- and loss-of-function studies likewise revealed that SCARA5 acts as a mediator of adipocyte commitment and differentiation in both A33 and C3H10T1/2 cells. RNAi-mediated knockdown of SCARA5 in A33 cells markedly inhibited the adipogenic potential, whereas overexpression of SCARA5 enhanced adipocyte differentiation in C3H10T1/2 cells. We also demonstrated that the focal adhesion kinase (FAK) and ERK signaling pathways is associated with the SCARA5-mediated response, thereby modulating adipocyte lineage commitment and adipocyte differentiation. Additionally, glucocorticoids induced the expression of SCARA5 in differentiating adipocytes through glucocorticoids response elements (GRE) in the SCARA5 promoter. Taken together, our study demonstrates that SCARA5 is a positive regulator in adipocyte lineage commitment and early adipogenesis in mesenchymal stem cells.

Suppression of PPARγ-mediated monoacylglycerol O-acyltransferase 1 expression ameliorates alcoholic hepatic steatosis.

Alcohol consumption is one of the major causes of hepatic steatosis, fibrosis, cirrhosis, and superimposed hepatocellular carcinoma. Ethanol metabolism alters the NAD(+)/NADH ratio, thereby suppressing the activity of sirtuin family proteins, which may affect lipid metabolism in liver cells. However, it is not clear how long-term ingestion of ethanol eventually causes lipid accumulation in liver. Here, we demonstrate that chronic ethanol ingestion activates peroxisome proliferator-activated receptor γ (PPARγ) and its target gene, monoacylglycerol O-acyltransferase 1 (MGAT1). During ethanol metabolism, a low NAD(+)/NADH ratio repressed NAD-dependent deacetylase sirtuin 1 (SIRT1) activity, concomitantly resulting in increased acetylated PPARγ with high transcriptional activity. Accordingly, SIRT1 transgenic mice exhibited a low level of acetylated PPARγ and were protected from hepatic steatosis driven by alcohol or PPARγ2 overexpression, suggesting that ethanol metabolism causes lipid accumulation through activation of PPARγ through acetylation. Among the genes induced by PPARγ upon alcohol consumption, MGAT1 has been shown to be involved in triglyceride synthesis. Thus, we tested the effect of MGAT1 knockdown in mice following ethanol consumption, and found a significant reduction in alcohol-induced hepatic lipid accumulation. These results suggest that MGAT1 may afford a promising approach to the treatment of fatty liver disease.

Caffeine inhibits adipogenesis through modulation of mitotic clonal expansion and the AKT/GSK3 pathway in 3T3-L1 adipocytes.

Caffeine has been proposed to have several beneficial effects on obesity and its related metabolic diseases; however, how caffeine affects adipocyte differentiation has not been elucidated. In this study, we demonstrated that caffeine suppressed 3T3-L1 adipocyte differentiation and inhibited the expression of CCAAT/enhancer binding protein (C/EBP)α and peroxisome proliferator-activated receptor (PPAR)γ, two main adipogenic transcription factors. Anti-adipogenic markers, such as preadipocyte secreted factor (Pref)-1 and Krüppel-like factor 2, remained to be expressed in the presence of caffeine. Furthermore, 3T3-L1 cells failed to undergo typical mitotic clonal expansion in the presence of caffeine. Investigation of hormonal signaling revealed that caffeine inhibited the activation of AKT and glycogen synthase kinase (GSK) 3 in a dose-dependent manner, but not extracellular signal-regulated kinase (ERK). Our data show that caffeine is an anti-adipogenic bioactive compound involved in the modulation of mitotic clonal expansion during adipocyte differentiation through the AKT/GSK3 pathway. [BMB Reports 2016; 49(2): 111-115].

Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis.

Glucocorticoids are associated with obesity, but the underlying mechanism by which they function remains poorly understood. Previously, we showed that small G protein Dexras1 is expressed by glucocorticoids and leads to adipocyte differentiation. In this study, we explored the mechanism by which Dexras1 mediates adipogenesis and show a link to the insulin-like growth factor-1 (IGF-1) signaling pathway. Without Dexras1, the activation of MAPK and subsequent phosphorylation of CCAAT/enhancer binding protein ß (C/EBPß) is abolished, thereby inhibiting mitotic clonal expansion and further adipocyte differentiation. Dexras1 translocates to the plasma membrane upon insulin or IGF-1 treatment, for which the unique C-terminal domain (amino acids 223-276) is essential. Dexras1-dependent MAPK activation is selectively involved in the IGF-1 signaling, because another Ras protein, H-ras localized to the plasma membrane independently of insulin treatment. Moreover, neither epidermal growth factor nor other cell types shows Dexras1-dependent MAPK activation, indicating the importance of Dexras1 in IGF-1 signaling in adipogenesis. Dexras1 interacts with Shc and Raf, indicating that Dexras1-induced activation of MAPK is largely dependent on the Shc-Grb2-Raf complex. These results suggest that Dexras1 is a critical mediator of the IGF-1 signal to activate MAPK, linking glucocorticoid signaling to IGF-1 signaling in adipogenesis.