Neuropeptide Y (NPY)/Agouti-related protein (AgRP) neurons in the arcuate nucleus of the hypothalamus are part of a neuroendocrine feedback loop that regulates feeding behavior and glucose homeostasis. NPY/AgRP neurons sense peripheral signals (including the hormones leptin, insulin, and ghrelin) and integrate those signals with inputs from other brain regions. These inputs modify both long-term changes in gene transcription and acute changes in the electrical activity of these neurons, leading to a coordinated response to maintain energy and glucose homeostasis. However, the mechanisms by which the hormones insulin and leptin acutely modify the electrical activity of these neurons remain unclear. In this study, we show that loss of the phosphoinositide 3-kinase catalytic subunits p110α and p110β in AgRP neurons abrogates the leptin- and insulin-induced inhibition of AgRP neurons. Moreover, continual disruption of p110α and p110β in AgRP neurons results in increased weight gain. The increased adiposity was concomitant with a hypometabolic phenotype: decreased energy expenditure independent of changes in food intake. Deficiency of p110α and p110β in AgRP neurons also impaired glucose homeostasis and insulin sensitivity. In summary, these data highlight the requirement of both p110α and p110β in AgRP neurons for the proper regulation of energy balance and glucose homeostasis.

Background Worldwide, the United States has the highest incarceration rate per capita. Thousands of people are released from US correctional facilities each year, including many who are impacted by HIV infection and substance use disorder (SUD), two frequently comorbid conditions that present multiple challenges upon reentry. Reentry and care engagement research involving justice-involved people with HIV (PWH) with comorbid SUD has been largely limited to the perspective of those released. To formulate effective interventions for this population aimed at maintaining health and reducing recidivism, it is crucial to collect data from formerly incarcerated individuals with firsthand experience of the reentry process as well as other actors within the reentry framework. Insights from medical and legal service providers working in reentry systems have the potential to address key implementation concerns. To inform an intervention aimed at helping recently-released individuals PWH and SUD, we conducted a qualitative study to assess barriers and facilitators to community reentry from the perspectives of diverse consumers and providers of medical, legal, and reentry services. Results Fifteen stakeholders within XXX County participated in in-person interviews. Results indicated that 1) Patients/clients emphasized psychosocial support and individual attitude more than medical and legal participants, who chiefly focused on logistical factors such as finances, housing, and transportation; 2) Patients/clients expressed both medical and legal needs during the reentry period, though medical providers and participants from legal entities mainly expressed concerns limited to their respective scopes of work; 3) All three participant groups underscored the need for a low-barrier, collaborative, patient-centered approach to reentry with the goal of achieving self-sufficiency. Conclusions Findings support and extend existing literature detailing the barriers and facilitators to successful reentry. Our findings underscore the notion that an effective reentry intervention addresses both medical and legal needs, includes an individualized approach that incorporates psychosocial needs, and focuses on establishing self-sufficiency.

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