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Forkhead transcription factor 3 (FOXA3) has been shown to regulate metabolism and development. Hepatic FOXA3 is reduced in obesity and fatty liver disease. However, the role of hepatic FOXA3 in regulating obesity or steatohepatitis remains to be investigated. In this work, C57BL/6 mice were i.v. injected with AAV8-ALB-FOXA3 or the control virus. The mice were then fed a chow or Western diet for 16 weeks. The role of hepatic FOXA3 in energy metabolism and steatohepatitis was investigated. Plasma bile acid composition and the role of Takeda G protein-coupled receptor 5 (TGR5) in mediating the metabolic effects of FOXA3 were determined. Overexpression of hepatic FOXA3 reduced hepatic steatosis in chow-fed mice and attenuated Western diet-induced obesity and steatohepatitis. FOXA3 induced lipolysis and inhibited hepatic genes involved in bile acid uptake, resulting in elevated plasma bile acids. The beneficial effects of hepatic FOXA3 overexpression on Western diet-induced obesity and steatohepatitis were abolished in Tgr5-/- mice. Our data demonstrate that overexpression of hepatic FOXA3 prevents Western diet-induced obesity and steatohepatitis via activation of TGR5.
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Dieta Ocidental , Fator 3-gama Nuclear de Hepatócito , Fígado , Camundongos Endogâmicos C57BL , Obesidade , Receptores Acoplados a Proteínas G , Animais , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Obesidade/metabolismo , Obesidade/genética , Obesidade/etiologia , Camundongos , Fator 3-gama Nuclear de Hepatócito/metabolismo , Fator 3-gama Nuclear de Hepatócito/genética , Fígado/metabolismo , Dieta Ocidental/efeitos adversos , Masculino , Fígado Gorduroso/metabolismo , Fígado Gorduroso/genética , Fígado Gorduroso/etiologia , Ácidos e Sais Biliares/metabolismoRESUMO
Parental communication about sex is an important aspect of sexual socialization. However, research has primarily focused on sexual communication's presence, frequency, or topics, with less research on the specific messages parents communicate. Further, few studies have differentiated between communication received before and after youth initiated sex. Therefore, in this paper, we coded open-ended survey responses to explore the sex-related messages young adults report receiving from their caregiver(s) before they began engaging in sex. As part of a larger study, 381 U.S. young adults (Mage = 21.0 years, SD = 2.0) completed an online survey and responded to an open-ended question about messages their caregiver(s) communicated before they began engaging in sex. Participants identified as cisgender women (62.2%), cisgender men (12.1%), and gender diverse (25.7%), and were primarily lesbian, gay, bisexual, queer, questioning, or otherwise non-heterosexual (LGBQ+; 70.6%) young adults. Through thematic analysis, we identified six themes for caregivers' sex-related messages: sex-restrictive, safety and consequences, no, negative, sex-positive, and informational messages. In addition, we found that messages varied by young adults' gender identity and sexual orientation. Our findings suggest that young adults may not receive proper education about healthy sexual relationships and demonstrate the need for interventions with caregivers, as well as sexual health resources for adolescents and young adults, particularly LGBTQ+ youth.
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RATIONALE: Coronary collateral growth is a natural bypass for ischemic heart diseases. It offers tremendous therapeutic benefit, but the process of coronary collateral growth isincompletely understood due to limited preclinical murine models that would enable interrogation of its mechanisms and processes via genetic modification and lineage tracing. Understanding the processes by which coronary collaterals develop can unlock new therapeutic strategies for ischemic heart disease. OBJECTIVE: To develop a murine model of coronary collateral growth by repetitive ischemia and investigate whether capillary endothelial cells could contribute to the coronary collateral formation in an adult mouse heart after repetitive ischemia by lineage tracing. METHODS AND RESULTS: A murine model of coronary collateral growth was developed using short episodes of repetitive ischemia. Repetitive ischemia stimulation resulted in robust collateral growth in adult mouse hearts, validated by high-resolution micro-computed tomography. Repetitive ischemia-induced collateral formation compensated ischemia caused by occlusion of the left anterior descending artery. Cardiac function improved during ischemia after repetitive ischemia, suggesting the improvement of coronary blood flow. A capillary-specific Cre driver (Apln-CreER) was used for lineage tracing capillary endothelial cells. ROSA mT/mG reporter mice crossed with the Apln-CreER transgene mice underwent a 17 days' repetitive ischemia protocol for coronary collateral growth. Two-photon and confocal microscopy imaging of heart slices revealed repetitive ischemia-induced coronary collateral growth initiated from sprouting Apelin+ endothelial cells. Newly formed capillaries in the collateral-dependent zone expanded in diameter upon repetitive ischemia stimulation and arterialized with smooth muscle cell recruitment, forming mature coronary arteries. Notably, pre-existing coronary arteries and arterioles were not Apelin+, and all Apelin+ collaterals arose from sprouting capillaries. Cxcr4, Vegfr2, Jag1, Mcp1, and Hif1⺠mRNA levels in the repetitive ischemia-induced hearts were also upregulated at the early stage of coronary collateral growth, suggesting angiogenic signaling pathways are activated for coronary collaterals formation during repetitive ischemia. CONCLUSIONS: We developed a murine model of coronary collateral growth induced by repetitive ischemia. Our lineage tracing study shows that sprouting endothelial cells contribute to coronary collateral growth in adult mouse hearts. For the first time, sprouting angiogenesis is shown to give rise to mature coronary arteries in response to repetitive ischemia in the adult mouse hearts.
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Células Endoteliais , Isquemia Miocárdica , Animais , Apelina/metabolismo , Circulação Colateral/fisiologia , Vasos Coronários/metabolismo , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Isquemia/metabolismo , Camundongos , Isquemia Miocárdica/metabolismo , Neovascularização Fisiológica/fisiologia , Microtomografia por Raio-XRESUMO
Sexual and romantic orientations are often considered one and the same, and attitudes about engaging in sexual behavior are assumed to be predominantly positive. The current study explored the concordance between sexual and romantic orientations among allosexual and asexual adults as well as the frequency with which they identify as having a sex-positive, sex-neutral, or sex-averse attitude. As expected, allosexual adults were largely sex-positive (82%) and almost all (89%) had a romantic orientation that matched their sexual orientation. In contrast, we found that only 37% of asexual adults had concordant sexual and romantic orientations and that most asexual adults self-identify as either sex-neutral (41%) or sex-averse (54%). Further, we used a semantic differential task to assess sexual intimacy attitudes and how they varied for adults based on sexual attitude. Asexual adults, regardless of sexual attitude, had less positive attitudes overall than allosexual adults. Interestingly, aromantic asexual adults did not have more negative attitudes about sexual intimacy than romantic asexual participants. Although asexual adults held less positive attitudes about sex than allosexual adults, there was considerable heterogeneity within our asexual sample. The current study provides further insight into the concordance between romantic and sexual orientation, and the associations among sexual and intimacy attitudes for both allosexual and asexual adults. These findings will have implications for future research on how asexual adults navigate romantic relationships.
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Comportamento Sexual , Disfunções Sexuais Psicogênicas , Adulto , Afeto , Atitude , Feminino , Humanos , MasculinoRESUMO
Many adolescents and young adults have mixed feelings about their experience of first vaginal intercourse, experiencing both positive consequences like physical satisfaction and love, as well as negative consequences like guilt and anxiety. However, no study has examined the patterns of consequences individuals experience after first vaginal intercourse, which can provide a more nuanced sense of young adults' feelings. We used latent class analysis to examine consequences of first vaginal intercourse in a longitudinal study of college students in the Northeastern United States (N = 191; 45.6% female, 30.9% White/European American, 23.6% Asian American/Pacific Islander, 22.5% Hispanic/Latino, 14.7% Black/African American, 8.4% multiracial). For male college students, classes included Multidimensional Positive (49.4%), Intimacy and Satisfaction (4.39%), and Guilt and Regret (16.22%). For female college students, classes included Intimacy, Satisfaction, and Pain (40.84%), Primarily Negative (31.11%), and Mixed Feelings (20.86%). For male students, age at first vaginal intercourse, first intercourse with a non-relationship partner, religiosity, and non-use of contraceptives were associated with class membership; for female students, first intercourse with a non-relationship partner was associated with being* in classes marked by multiple negative consequences. Findings differ by gender and are partially in line with the sexual double standard, but provide a more nuanced picture, with the majority of both male and female college students likely to report positive consequences, specifically intimacy and physical satisfaction.
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Coito , Comportamento Sexual , Adulto Jovem , Adolescente , Masculino , Feminino , Humanos , Estudos Longitudinais , Parceiros Sexuais , EstudantesRESUMO
Despite increasing efforts to better understand sexual and gender minority youth (SGMY), asexual youth remain understudied. This study examines differences in health, family support, and school safety among asexual youth (n = 938) from a national study of SGMY (N = 17,112) ages 13-17. Compared to non-asexual youth, asexual youth were more likely to identify as transgender and report a disability, and less likely to identify as Black or Hispanic/Latino. Transgender (versus cisgender) asexual youth fared worse on most study outcomes. Cisgender asexual (versus cisgender non-asexual) youth fared worse on all study outcomes. Transgender asexual (versus transgender non-asexual) youth reported lower sexuality-related family support. These findings underscore the role of gender identity in understanding the experiences of asexual youth.
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Minorias Sexuais e de Gênero , Pessoas Transgênero , Adolescente , Feminino , Identidade de Gênero , Humanos , Masculino , Instituições Acadêmicas , Comportamento SexualRESUMO
Desire discrepancies are a common source of relationship conflict and one reason adults may seek couples counseling. Within romantic relationships, adults individually experience sexual and affectionate desire, but also experience desire relative to their partner. If desire discrepancies exist, partners may attempt to resolve these discrepancies. Thus, we examined adults' strategies for managing sexual and affectionate desire discrepancies. Our sample consisted of 300 adults (45% women; Mage = 29.5; 86.3% LGBTQ+) who were in a romantic relationship and reported a desire discrepancy. Thematic analysis revealed five strategies for managing desire discrepancies: alternative behaviors, communication, doing nothing, engaging in behaviors anyway, and giving control to a specific partner. Adults reported similar strategies for resolving sexual and affectionate desire discrepancies. Perceived effectiveness and strategies varied by whether adults thought that their discrepancies were problematic. Our findings hold implications for clinicians approaching problematic desire discrepancies, and suggest strategies that may promote effective resolutions.
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Relações Interpessoais , Comportamento Sexual , Parceiros Sexuais , Humanos , Feminino , Adulto , Masculino , Parceiros Sexuais/psicologia , Comportamento Sexual/psicologia , Adulto Jovem , Pessoa de Meia-Idade , LibidoRESUMO
OBJECTIVE: The adipose tissue-liver axis is a major regulator of the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Retinoic acid signaling plays an important role in development and metabolism. However, little is known about the role of adipose retinoic acid signaling in the development of obesity-associated NAFLD. In this work, the aim was to investigate whether and how retinoic acid receptor alpha (RARα) regulated the development of obesity and NAFLD. METHODS: RARα expression in adipose tissue of db/db or ob/ob mice was determined. Rarαfl/fl mice and adipocyte-specific Rarα-/- (RarαAdi-/- ) mice were fed a chow diet for 1 year or high-fat diet (HFD) for 20 weeks. Primary adipocytes and primary hepatocytes were co-cultured. Metabolic regulation and inflammatory response were characterized. RESULTS: RARα expression was reduced in adipose tissue of db/db or ob/ob mice. RarαAdi-/- mice had increased obesity and steatohepatitis (NASH) when fed a chow diet or HFD. Loss of adipocyte RARα induced lipogenesis and inflammation in adipose tissue and the liver and reduced thermogenesis. In the co-culture studies, loss of RARα in adipocytes induced inflammatory and lipogenic programs in hepatocytes. CONCLUSIONS: The data demonstrate that RARα in adipocytes prevents obesity and NASH via inhibiting lipogenesis and inflammation and inducing energy expenditure.
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Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Adipócitos/metabolismo , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético , Inflamação/metabolismo , Lipogênese/genética , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/complicações , Receptor alfa de Ácido Retinoico/genética , Receptor alfa de Ácido Retinoico/metabolismo , Tretinoína/metabolismoRESUMO
BACKGROUND: Krüppel-like factor 10 (KLF10), a zinc finger transcription factor, plays a pivotal role in modulating TGF-ß-mediated cellular processes such as growth, apoptosis, and differentiation. Recent studies have implicated KLF10 in regulating lipid metabolism and glucose homeostasis. This study aimed to elucidate the precise role of hepatic KLF10 in developing metabolic dysfunction-associated steatohepatitis (MASH) in diet-induced obese mice. METHODS: We investigated hepatic KLF10 expression under metabolic stress and the effects of overexpression or ablation of hepatic KLF10 on MASH development and lipidemia. We also determined whether hepatocyte nuclear factor 4α (HNF4α) mediated the metabolic effects of KLF10. RESULTS: Hepatic KLF10 was downregulated in MASH patients and genetically or diet-induced obese mice. AAV8-mediated overexpression of KLF10 in hepatocytes prevented Western diet-induced hypercholesterolemia and steatohepatitis, whereas inactivation of hepatocyte KLF10 aggravated Western diet-induced steatohepatitis. Mechanistically, KLF10 reduced hepatic triglyceride and free fatty acid levels by inducing lipolysis and fatty acid oxidation and inhibiting lipogenesis, and reducing hepatic cholesterol levels by promoting bile acid synthesis. KLF10 highly induced HNF4α expression by directly binding to its promoter. The beneficial effect of KLF10 on MASH development was abolished in mice lacking hepatocyte HNF4α. In addition, the inactivation of KLF10 in hepatic stellate cells exacerbated Western diet-induced liver fibrosis by activating the TGF-ß/SMAD2/3 pathway. CONCLUSIONS: Our data collectively suggest that the transcription factor KLF10 plays a hepatoprotective role in MASH development by inducing HNF4α. Targeting hepatic KLF10 may offer a promising strategy for treating MASH.
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Fatores de Transcrição de Resposta de Crescimento Precoce , Fígado Gorduroso , Fator 4 Nuclear de Hepatócito , Fatores de Transcrição Kruppel-Like , Animais , Fator 4 Nuclear de Hepatócito/metabolismo , Fator 4 Nuclear de Hepatócito/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Camundongos , Humanos , Masculino , Fatores de Transcrição de Resposta de Crescimento Precoce/metabolismo , Fatores de Transcrição de Resposta de Crescimento Precoce/genética , Fígado Gorduroso/metabolismo , Fígado Gorduroso/etiologia , Camundongos Endogâmicos C57BL , Metabolismo dos Lipídeos , Fígado/metabolismo , Hepatócitos/metabolismo , Camundongos KnockoutRESUMO
Prior experience with physical behaviors - both sexual and affectionate - is common among adults in romantic relationships. However, less is known about differences in physical behaviors for asexual and allosexual adults, and these differences may explain how asexual adults navigate sexuality in romantic relationships. In this study we used sexual script theory to examine asexual (n = 109; 59% women; Mage = 27.7) and allosexual adults' (n = 403; 58% women; Mage = 29.0) prior experiences with and future likelihood to engage in sexual and affectionate behaviors in romantic relationships, and how these differences vary by gender. Asexual adults had less prior experience with and were less likely to intend to engage in future physical behaviors than allosexual adults. There were some gender differences in past experience and future likelihood. Prior experience with physical behaviors was associated with expected likelihood to engage in these behaviors for allosexual and asexual adults, although the association was stronger for asexual adults. These results have implications for how asexual adults engage in physical behaviors, and how differing interest in physical behaviors may cause conflict within asexual-allosexual couples.
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Comportamento Sexual , Sexualidade , Humanos , Adulto , Feminino , Masculino , Prazer , Fatores SexuaisRESUMO
Research suggests that COVID-19-related restrictions affected individuals' ability to engage in relationship maintenance behaviors and have led to poorer romantic relationship quality. Poor relationship quality may be especially problematic for lesbian, gay, bisexual, transgender, queer or questioning, and otherwise non-heterosexual or-cisgender (LGBTQ+) college students, who often lack family support and are at greater risk for mental health issues. We used a social exchange theory lens to examine correlates of relationship satisfaction for LGBTQ+ college students during the early months of the pandemic. The analytic sample consists of 175 LGBTQ+ students (Mage = 20.5) who completed an online survey and reported being in a romantic relationship. Our findings demonstrate that LGBTQ+ students with more supportive partners were more satisfied with their relationships. These results can inform clinicians how to better support LGBTQ+ college couples when they experience relationship stress.
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In the United States (U.S.), Black sexual minority men (BSMM) are disproportionately burdened by HIV. Prevention advances, such as HIV pre-exposure prophylaxis (PrEP), play a key role in reducing HIV transmission and improving our understanding of sexual expression and health. Despite these advances, little is known regarding the potential link between PrEP use and positive sexuality, including the benefits that BSMM see in accessing PrEP. We conducted a thematic analysis of 32 interviews with BSMM in the Southern U.S. regarding their PrEP beliefs. We developed five themes: (1) Sexual freedom, (2) Agency and empowerment, (3) Making PrEP normative, (4) Behavioral health practices, and (5) Committed relationship tensions. Our findings suggest that BSMM are increasingly concerned about freedom of choice and invested in sexual empowerment as related to their PrEP use. Further, unanticipated benefits, community support, and relationship tensions are salient factors in considerations of PrEP use among BSMM. These findings have implications for how we might understand a broader movement toward sexual empowerment and positivity, and the pivotal role that PrEP serves in this movement.
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Infecções por HIV , Minorias Sexuais e de Gênero , Masculino , Humanos , Estados Unidos , Homossexualidade Masculina , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Negro ou Afro-Americano , Comportamento SexualRESUMO
The coronavirus disease (COVID-19) pandemic has negatively impacted the well-being of many college students, particularly lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ +) students who are already at a disproportionate risk for negative mental health and well-being outcomes. To identify potential risk and protective factors we examined LGBTQ + college students' disclosure of sexual orientation, gender identity, or both (SOGI) to mothers and fathers, living arrangements (whether or not students lived with mothers and fathers), social support from family and friends, and parent-child relationship quality and their association with stress, depressive symptoms, anxiety symptoms, and problem drinking during the pandemic. LGBTQ + college students (N = 366; Mage = 20.4) completed an online survey. Students who reported more social support from family and friends and better quality relationships with mothers or fathers had better well-being and were less likely to perceive a substantial decrease in their well-being due to the pandemic. In contrast, SOGI disclosure and whether or not students lived with mothers or fathers were generally unrelated to well-being. Findings suggest that universities should consider offering mental health resources for students living on- and off-campus, and that clinical professionals should consider strategies to help these young adults identify and maintain support systems and highlight the value of positive parent-child relationships. (PsycInfo Database Record (c) 2022 APA, all rights reserved).