Modulation of adipocyte genes by signal transducers and activators of transcription

Members of the STAT transcription factor family are expressed in adipocytes, including STATs 1, 3, 5A, 5B, and 6. Although STATs 1 and 5 proteins are known to be induced during adipogenesis, the functions of these STATs in mature adipocytes are not known. Hence we have sought to identify adipocyte genes which are transcriptionally regulated by STATs to elucidate a role of these proteins in fat cells. We have characterized STAT binding sites in the promoters of four adipocyte genes, PPARγ2, LPL, FAS and C/EBPδ. PPARγ2 expression decreases in adipocytes following exposure to IFNγ, an activator of STAT1. IFNγ induces the binding of STAT1 to a site in the PPARγ2 promoter. Furthermore, the STAT1 binding site is required for IFNγ regulation of the PPARγ2 promoter in vitro. Although CT-1 and LIF induced STAT1 binding to the PPARγ2 promoter, only CT-1 substantially modulated expression of PPARγ2. We have also identified a STAT1 binding site in the promoter of LPL, which is bound by STAT1 following treatment of 3T3-L1 adipocytes with IFNγ. In addition, LPL protein levels are downregulated by IFNγ treatment. Treatment with PRL, an activator of STAT5A, decreased levels of FAS protein and mRNA in adipocytes. Regulation of the rat FAS promoter by PRL required a region of the promoter which contained a STAT5 binding site. Binding to this site by STAT5A was activated by PRL treatment and was highly specific. Finally, in our analysis on the effects of LIF on adipocytes, we determined that the expression SOCS3 and C/EBPδ mRNA transiently increases following treatment of adipocytes with LIF. We identified three STAT1 binding sites within the C/EBPδ promoter, which we hypothesize mediate the induction of C/EBPδ by LIF. Although LIF did not profoundly affect adipogenesis or basal and insulin-stimulated glucose uptake, chronic treatment with LIF abrogated the level of SREBP1 and FAS proteins. In summary, our studies suggest that STAT1 and STAT5 serve to limit synthesis of lipids in mature fat cells, limiting expansion of adipocytes and accretion of adipose tissue. The identification of PPARγ, FAS, and LPL as STAT-regulated genes provides insight into the molecular mechanisms of energy homeostasis, adipocyte physiology and the action of cytokines in fat

Effects of leukemia inhibitory factor on 3T3-L1 adipocytes

Leukemia inhibitory factor (LIF) is a member of the gp130 cytokine family and signals through the receptor complex of gp130 and the LIF receptor (LIFR) to activate the JAK/STAT signaling cascade. Since LIF activates STATs 1 and 3 in adipocytes, we examined the effects of LIF on 3T3-L1 adipocytes. Our studies clearly demonstrate that LIF treatment had minimal effects on adipocyte differentiation as judged by marker gene expression, but did inhibit triacylglyceride (TAG) accumulation during adipogenesis. Acute treatment with LIF resulted in increased expression of suppressors of cytokine signaling-3 (SOCS3) and CCAAT/enhancer-binding protein-δ (C/EBPδ) mRNA in 3T3-L1 adipocytes. Moreover, the upregulation of C/EBPδ correlated with binding to three sites in the C/EBPδ promoter by LIF-activated protein complexes that contained STAT1 and not STAT3. Chronic treatment with LIF resulted in decreased protein levels of sterol regulatory element binding protein-1 (SREBP1) and fatty acid synthase (FAS), but had no effect on the expression of other adipocyte marker proteins or on TAG levels in mature 3T3-L1 adipocytes. LIF had a small effect on insulin-stimulated glucose uptake in 3T3-L1 adipocytes, but did not cause insulin resistance following chronic treatment. These findings indicate that LIF has similar and distinct effects in comparison with the effects of other gp130 cytokines on cultured fat cells. In summary, our results support a role for LIF in the regulation of proteins involved in lipid synthesis and in the modulation of signal transduction pathways in 3T3-L1 adipocytes. © 2005 Society for Endocrinology

The regulation of fatty acid synthase by STAT5A

Growth hormone (GH) diminishes adipose tissue mass in vivo and decreases expression and activity of fatty acid synthase (FAS) in adipocytes. GH and prolactin (PRL) are potent activators of STAT5 and exert adipogenic and antiadipogenic effects in adipocytes. In this study, we demonstrate that GH and PRL decrease the mRNA and protein levels of FAS in 3T3-L1 adipocytes. We present evidence that indicates that FAS is repressed at the level of transcription. In addition, PRL responsiveness was shown to exist between -1,594 and -700 of the rat FAS promoter. Moreover, responsiveness to PRL was abolished with mutation of a site at position -908 to -893, which we have shown to bind STAT5A in a PRL-dependent manner. Taken together, these data strongly suggest that PRL directly represses expression of FAS in adipocytes through STAT5A binding to the -908 to -893 site. Furthermore, our results indicate that STAT5A has an antilipogenic function in adipocytes and may contribute to the regulation of energy balance. © 2005 by the American Diabetes Association

Evaluating the Impact of Fishery-Related Claw Removal On Diet, Consumption Rate, Energetics and Reproduction In the Florida Stone Crab (Menippe Spp.)

Many global fisheries are overexploited and working towards the development of sustainable fishing methods. Claw based crab fisheries, such as the Florida stone crab (Menippe mercenaria, M. adina, and hybrids) fishery, use unique fishing techniques that reduce the overall mortality of harvested organisms. For example, the Florida stone crab fishery is regulated by requiring that fisherman only harvest crab claws and requires that fishermen return the live crab to the water following harvesting. This process takes advantage of the ability of crabs to autotomize and regenerate their claws, and enables crabs to re-enter the fishery in subsequent years if they survive. Though this fishery is currently considered to be sustainable, fishery-related claw loss may negatively influence the population through multiple pathways. The objectives of this study were to demonstrate how fishery-related claw loss influences Florida stone crab diet choice, consumption over time, and energy allocation following simple dynamic energy budget theory, with the ultimate goal of determining how these factors influence the reproduction of harvested individuals. I demonstrated that one-clawed Florida stone crabs do not switch their diet to more easily managed food items, such as algae or sponge, following claw removal. However, I found that one-clawed crabs consume fewer bivalves than two-clawed crabs, and they do not improve in their ability to crack mussels over time, suggesting that decreased foraging capacity will remain until the regenerative molt. I found that one-clawed Florida stone crabs do not alter their energy storage patterns prior to the reproductive season, suggesting that the energy for both reproduction and claw removal will be derived from the same energy stores. Lastly, I found that regenerating a crusher claw has the potential to take energy away from reproduction; however, the energetic implications of decreased consumption following claw loss far outweigh the energetic costs of claw regeneration. The results of this study indicate that Florida stone crabs are likely to suffer from severe energetic constraints resulting from claw removal, which could limit growth, claw regeneration, reproduction and survival of harvested crabs

Understanding ATV use: perceptions of impact and actual impact on dune systems in New Brunswick, Canada

Increases in illegal all-terrain vehicle (ATV) in New Brunswick (NB), Canada, causes concern for the integrity of beaches and dune systems. Using self-administered questionnaires (n=289), we compared three NB communities: Pointe-Sapin, Escuminac, and Miscou Island. Findings show that Miscou residents perceived impacts upon dune photographs as higher than Pointe-Sapin and were more accepting of ATV management than Pointe-Sapin. In concert, we compared plant community characteristics between ATV trails on Miscou Island and non-ATV use dunes in Kouchibouguac National Park and found that where ATV trail ruts were greatest, measures of species richness increased with distance from the trail. Based on residents perceived main threat to dunes, residents may have ranked the dune photographs by vegetation cover which was seen to decrease due to rut depth on direct plots. Few studies link human dimensions with recreation ecology on coastal sand dunes, and these findings provide direction for managers in NB

What makes local energy projects acceptable? Probing the connection between ownership structures and community acceptance

Funding: Social Sciences and Humanities Research Council of Canada (752-2019-0520), Rothermere Foundation, Canadian Centennial Scholarship Fund, University of St Andrews.Community ownership of wind energy has been found to increase acceptance, but the reasons for this are poorly understood. Here, we compare different communities’ attitudes towards local onshore wind energy projects in order to gain a deeper understanding of the characteristics of ownership which are conducive to community acceptance. Using a postal survey in Scotland (n = 318), we compared three communities with varying degrees of ownership regarding their (1) support for the local wind project; (2) perceptions of energy justice; (3) perceived impacts; and (4) ownership and benefit preferences. One-way ANOVAs and the Potential for Conflict Index2 identified that residents in the two communities with a degree of ownership were more associated with greater acceptance, processes, and outcomes (i.e. more just and inclusive development processes and more fairly distributed benefits and impacts), than residents living near the privately-owned development. Additionally, we provide evidence that a co-operative can achieve similar acceptance and energy justice as a fully community-owned project. Overall, the results indicate that policymakers should take seriously the connection between the tenets of energy justice and ownership models in their policy and planning efforts.Publisher PDFPeer reviewe

Effects of cardiotrophin on adipocytes

Cardiotrophin (CT-1) is a naturally occurring protein member of the interleukin (IL)-6 cytokine family and signals through the gp130/leukemia inhibitory factor receptor (LIFR) heterodimer. The formation of gp130/ LIFR complex triggers the auto/trans-phosphorylation of associated Janus kinases, leading to the activation of Janus kinase/STAT and MAPK (ERK1 and -2) signaling pathways. Since adipocytes express both gp130 and LIFR proteins and are responsive to other IL-6 family cytokines, we examined the effects of CT-1 on 3T3-L1 adipocytes. Our studies have shown that CT-1 administration results in a dose- and time-dependent activation and nuclear translocation of STAT1, -3, -5A, and -5B as well as ERK1 and -2. We also confirmed the ability of CT-1 to induce signaling in fat cells in vivo. Our studies revealed that neither CT-1 nor ciliary neurotrophic factor treatment affected adipocyte differentiation. However, acute CT-1 treatment caused an increase in SOCS-3 mRNA in adipocytes and a transient decrease in peroxisome proliferator-activated receptor γ (PPARγ) mRNA that was regulated by the binding of STAT1 to the PPARγ2 promoter. The effects of CT-1 on SOCS-3 and PPARγ mRNA were independent of MAPK activation. Chronic administration of CT-1 to 3T3-L1 adipocytes resulted in a decrease of both fatty acid synthase and insulin receptor substrate-1 protein expression yet did not effect the expression of a variety of other adipocyte proteins. Moreover, chronic CT-1 treatment resulted in the development of insulin resistance as judged by a decrease in insulin-stimulated glucose uptake. In summary, CT-1 is a potent regulator of signaling in adipocytes in vitro and in vivo, and our current efforts are focused on determining the role of this cardioprotective cytokine on adipocyte physiology

Exploring the relationship between sexual compulsivity and attentional bias to sex-related words in a cohort of sexually active individuals

Background/Aims: If sexual compulsivity and other addictive behaviours share common aetiology, contemporary proposals about the role of attentional processes in understanding addictive behaviours are relevant. Methods: To examine attentional biases for sex-related words amongst sexually active individuals and the relationship between sexual compulsivity and sexual behavioural engagement with attentional bias, 55 sexually active individuals completed a modified Stroop task and the sexual compulsivity scale. Results: Findings showed attentional bias towards sex-related stimuli among sexually active participants. In addition, amongst those with low levels of sexual compulsivity, levels of attentional bias were the same across all levels of sexual experience. Amongst those with higher levels of sexual compulsivity, greater attentional bias was linked with lower levels of sexual experience. Conclusion: Attentional preference for concern-related stimuli varies as a function of the interaction between how long a person has been active sexually and how compulsive their sexual behaviour is

Adoption of Mobile Apps for Depression and Anxiety: Cross-Sectional Survey Study on Patient Interest and Barriers to Engagement

BACKGROUND: Emerging research suggests that mobile apps can be used to effectively treat common mental illnesses like depression and anxiety. Despite promising efficacy results and ease of access to these interventions, adoption of mobile health (mHealth; mobile device-delivered) interventions for mental illness has been limited. More insight into patients\u27 perspectives on mHealth interventions is required to create effective implementation strategies and to adapt existing interventions to facilitate higher rates of adoption. OBJECTIVE: The aim of this study was to examine, from the patient perspective, current use and factors that may impact the use of mHealth interventions for mental illness. METHODS: This was a cross-sectional survey study of veterans who had attended an appointment at a single Veterans Health Administration facility in early 2016 that was associated with one of the following mental health concerns: unipolar depression, any anxiety disorder, or posttraumatic stress disorder. We used the Veteran Affairs Corporate Data Warehouse to create subsets of eligible participants demographically stratified by gender (male or female) and minority status (white or nonwhite). From each subset, 100 participants were selected at random and mailed a paper survey with items addressing the demographics, overall health, mental health, technology ownership or use, interest in mobile app interventions for mental illness, reasons for use or nonuse, and interest in specific features of mobile apps for mental illness. RESULTS: Of the 400 potential participants, 149 (37.3%, 149/400) completed and returned a survey. Most participants (79.9%, 119/149) reported that they owned a smart device and that they use apps in general (71.1%, 106/149). Most participants (73.1%, 87/149) reported interest in using an app for mental illness, but only 10.7% (16/149) had done so. Paired samples t tests indicated that ratings of interest in using an app recommended by a clinician were significantly greater than general interest ratings and even greater when the recommending clinician was a specialty mental health provider. The most frequent concerns related to using an app for mental illness were lacking proof of efficacy (71.8%, 107/149), concerns about data privacy (59.1%, 88/149), and not knowing where to find such an app (51.0%, 76/149). Participants expressed interest in a number of app features with particularly high-interest ratings for context-sensitive apps (85.2%, 127/149), and apps focused on the following areas: increasing exercise (75.8%, 113/149), improving sleep (73.2%, 109/149), changing negative thinking (70.5%, 105/149), and increasing involvement in activities (67.1%, 100/149). CONCLUSIONS: Most respondents had access to devices to use mobile apps for mental illness, already used apps for other purposes, and were interested in mobile apps for mental illness. Key factors that may improve adoption include provider endorsement, greater publicity of efficacious apps, and clear messaging about efficacy and privacy of information. Finally, multifaceted apps that address a range of concerns, from sleep to negative thought patterns, may be best received