The MRAP2 accessory protein directly interacts with melanocortin-3 receptor to enhance signaling.

The central melanocortin system links nutrition to energy expenditure, with melanocortin-4 receptor (MC4R) controlling appetite and food intake, and MC3R regulating timing of sexual maturation, rate of linear growth and lean mass accumulation. Melanocortin-2 receptor accessory protein-2 (MRAP2) is a single transmembrane protein that interacts with MC4R to potentiate it's signalling, and human mutations in MRAP2 cause obesity. Previous studies have been unable to consistently show whether MRAP2 affects MC3R activity.

LGBTQI Sexual Well-Being and Embodiment After Cancer: A Mixed-Methods Study.

This study examined lesbian, gay, bisexual, transgender, queer and intersex (LGBTQI) cancer patients' sexual well-being post-cancer, and the associations between sexual well-being and social support, physical concerns, distress, quality of life (QOL), and coping. We used a mixed-methods approach, including 430 surveys and 103 interviews, representing a range of tumor types, sexual and gender identities, age groups, and intersex status. The findings indicated that LGBTQI people with cancer experience declines in sexual well-being following cancer, which are associated with reduced QOL, greater physical concerns, and lower social support.

Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease.

Obesity is a major risk factor for many common diseases and has a substantial heritable component. To identify new genetic determinants, we performed exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare loss-of-function variants in two genes (BSN and APBA1) with effects substantially larger than those of well-established obesity genes such as MC4R.

A brainstem to hypothalamic arcuate nucleus GABAergic circuit drives feeding.

The obesity epidemic is principally driven by the consumption of more calories than the body requires. It is therefore essential that the mechanisms underpinning feeding behavior are defined. Neurons within the brainstem dorsal vagal complex (DVC) receive direct information from the digestive system and project to second-order regions in the brain to regulate food intake.

The vagus nerve mediates the physiological but not pharmacological effects of PYY on food intake.

Peptide YY (PYY) is a post-prandially released gut hormone with potent appetite-reducing activity, the mechanism of action of which is not fully understood. Unravelling how this system physiologically regulates food intake may help unlock its therapeutic potential, whilst minimising unwanted effects. Here we demonstrate that germline and post-natal targeted knockdown of the PYY preferring receptor (neuropeptide Y (NPY) Y2 receptor (Y2R)) in the afferent vagus nerve is required for the appetite inhibitory effects of physiologically-released PYY, but not peripherally administered pharmacological doses.

Are GLP-1R agonists the long-sought-after panacea for obesity?

Glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonists are hugely effective in the treatment of obesity. Originally developed for type 2 diabetes (T2D), these drugs cause dramatic weight loss in people with overweight or obesity, but how do they work, and are these therapeutics the long-sought-after solution to obesity? Here we explain the mechanisms of action of GLP-1R agonists in the context of weight loss and discuss their importance as therapeutics for obesity treatment.

Fetal manipulation of maternal metabolism is a critical function of the imprinted Igf2 gene.

Maternal-offspring interactions in mammals involve both cooperation and conflict. The fetus has evolved ways to manipulate maternal physiology to enhance placental nutrient transfer, but the mechanisms involved remain unclear. The imprinted Igf2 gene is highly expressed in murine placental endocrine cells.

Obesity medication lorcaserin activates brainstem GLP-1 neurons to reduce food intake and augments GLP-1 receptor agonist induced appetite suppression.

Objective: Overweight and obesity are endemic in developed countries, with a substantial negative impact on human health. Medications developed to treat obesity include agonists for the G-protein coupled receptors glucagon-like peptide-1 (GLP-1R; e.g.

Men, bodywork, health and the potentiality of performance and image-enhancing drugs.

In a qualitative study on masculinity, embodiment and sexuality, we interviewed men who were recreational gym-goers about their bodywork practices in Melbourne, Australia. We also asked whether the men had used performance and image-enhancing drugs (PIEDs) as an adjunct to their bodywork practices. While none had used PIEDs, all were considering, or had considered, using them.

HypoMap-a unified single-cell gene expression atlas of the murine hypothalamus.

The hypothalamus plays a key role in coordinating fundamental body functions. Despite recent progress in single-cell technologies, a unified catalog and molecular characterization of the heterogeneous cell types and, specifically, neuronal subtypes in this brain region are still lacking. Here, we present an integrated reference atlas, 'HypoMap,' of the murine hypothalamus, consisting of 384,925 cells, with the ability to incorporate new additional experiments.

Loss of Function of the Neural Cell Adhesion Molecule NrCAM Regulates Differentiation, Proliferation and Neurogenesis in Early Postnatal Hypothalamic Tanycytes.

Hypothalamic tanycytes are neural stem and progenitor cells, but little is known of how they are regulated. Here we provide evidence that the cell adhesion molecule, NrCAM, regulates tanycytes in the adult niche. NrCAM is strongly expressed in adult mouse tanycytes.

Traversing TechSex: benefits and risks in digitally mediated sex and relationships.

Background: Digital technologies play a significant role in people's sexual and intimate lives via smart phones, cameras, dating apps and social media. Although there is a large body of research on the potential risks posed by these technologies, research on benefits and pleasures is limited.

Methods: This study explored digital sexual practices, including perceptions of risks and benefits among a sample of Australian adults (n =445).

Development of a Sexual Quality of Life Questionnaire for Men-Who-Have-Sex-With-Men With Prostate Cancer.

Background: Prostate cancer (PCa) is often diagnosed early with prolonged survival, which makes sexual quality of life (QoL) an increasingly important treatment consideration, but existing QoL questionnaires have limited applicability for men who-have-sex-with-men (MSM) beyond penile erections and penetrative sex.

Aim: We aimed to create a validated survey instrument for assessing a variety of sexual activities beyond penile insertive sex for MSM after PCa treatment.

Methods: Based on our previously published survey findings, we have generated a prototype questionnaire with 13 different domains, reviewed by both healthy MSM and pilot-tested by MSM treated for PCa.

Attitudes, knowledge and practice behaviours of oncology health care professionals towards lesbian, gay, bisexual, transgender, queer and intersex (LGBTQI) patients and their carers: A mixed-methods study.

Objective: There is growing recognition that health care professionals (HCPs) and policy makers are insufficiently equipped to provide culturally competent care to lesbian, gay, bisexual, transgender, queer and intersex (LGBTQI) cancer patients and their families. We examined HCP attitudes, knowledge, and practices regarding LGBTQI cancer care using a mixed-methods research design.

Method: Surveys were completed by 357 oncology HCPs in nursing (40%), medical (24%), allied health (19%), and clinical leadership roles (11%); 48 of the surveyed HCPs were interviewed.

MC3R links nutritional state to childhood growth and the timing of puberty.

The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes.

High Coexpression of the Ghrelin and LEAP2 Receptor GHSR With Pancreatic Polypeptide in Mouse and Human Islets.

Islets represent an important site of direct action of the hormone ghrelin, with expression of the ghrelin receptor (growth hormone secretagogue receptor; GHSR) having been localized variably to alpha cells, beta cells, and/or somatostatin (SST)-secreting delta cells. To our knowledge, GHSR expression by pancreatic polypeptide (PP)-expressing gamma cells has not been specifically investigated. Here, histochemical analyses of Ghsr-IRES-Cre × Cre-dependent ROSA26-yellow fluorescent protein (YFP) reporter mice showed 85% of GHSR-expressing islet cells coexpress PP, 50% coexpress SST, and 47% coexpress PP + SST.

A survey of the mouse hindbrain in the fed and fasted states using single-nucleus RNA sequencing.

Objective: The area postrema (AP) and nucleus tractus solitarius (NTS) located in the hindbrain are key nuclei that sense and integrate peripheral nutritional signals and consequently regulate feeding behaviour. While single-cell transcriptomics have been used in mice to reveal the gene expression profile and heterogeneity of key hypothalamic populations, similar in-depth studies have not yet been performed in the hindbrain.

Methods: Using single-nucleus RNA sequencing, we provide a detailed survey of 16,034 cells within the AP and NTS of mice in the fed and fasted states.

Stigma as understood by key informants: A social ecological approach to gay and bisexual men's use of crystal methamphetamine for sex.

This paper explores the perceptions of 35 key informants (KIs) in a range of relevant health and community sectors regarding the stigmatisation of GBM's crystal methamphetamine use and sexual practice with view to informing stigma reduction efforts. A modified social ecological model was used to guide analysis and interpretation. At the individual level, KI participants indicated that crystal methamphetamine was used by some GBM to reduce the effects of internalised stigma.

Priorities and practices of risk reduction among gay and bisexual men in Australia who use crystal methamphetamine for sex.

Crystal methamphetamine (hereafter crystal) is associated with deleterious health outcomes, such as drug dependence and physical and mental health disorders. While some harms from crystal use can affect all users, there may be additional risks for people who combine the use of drug with sex. Compared with the broader population, gay and bisexual men in Australia report a higher prevalence of methamphetamine use, and crystal is the most commonly injected illicit drug among this population.

'It's like getting an Uber for sex': social networking apps as spaces of risk and opportunity in the Philippines among men who have sex with men.

The HIV epidemic in the Philippines has been expanding rapidly, with most newly diagnosed cases occurring among 'men who have sex with men' (MSM). New social contexts of HIV are evident in the evolving phenomenon of more MSM seeking partners online via social networking applications ('apps'). This study examines findings from a virtual ethnography of app use among MSM, focus group discussions with community-based healthcare workers, and key informant interviews with healthcare workers, policymakers and researchers in Metro Manila.

The significance and expectations of HIV cure research among people living with HIV in Australia.

Most people living with HIV (PLHIV) with reliable access to antiretroviral treatment (ART) have a life expectancy similar to uninfected populations. Despite this, HIV can negatively affect their social and psychological wellbeing. This study aimed to enhance understanding of the expectations PLHIV hold for HIV cure research and the implications this has for HIV cure research trials.

Destabilising the 'problem' of chemsex: Diversity in settings, relations and practices revealed in Australian gay and bisexual men's crystal methamphetamine use.

In Australia, the crystalline form of methamphetamine ("crystal") is a commonly used illicit substance associated with sexual activity among gay and bisexual men. Attention to psychoactive substance use among this population is the subject of increasing global concern regarding the intentional and simultaneous combination of sex and drugs, often referred to as "chemsex". While not all gay and bisexual men who use psychoactive substances report problematic use, those who do often become representative of chemsex practices more generally, and the harms they experience become attributable to all men who use drugs for sex.