Objective We examined whether deficiency of Shp2 signaling in forebrain neurons alters metabolic and cardiovascular regulation under various conditions and if it attenuates the anorexic and cardiovascular effects of leptin. We also tested whether forebrain Shp2 deficiency alters blood pressure (BP) and heart rate (HR) responses to acute stress. Design Forebrain Shp2-/- mice were generated by crossing Shp2flox/flox mice with CamKIIα-cre mice. At 22 to 24 weeks of age, mice were instrumented for telemetry for measurement of BP, HR and body temperature (BT). Oxygen consumption (VO2), energy expenditure and motor activity were monitored by indirect calorimetry. Results Shp2/CamKIIα-cre mice were heavier (46±3 vs 32±1 g), hyperglycemic, hyperleptinemic, hyperinsulinemic, and hyperphagic compared to Shp2flox/flox control mice. Shp2/CamKIIα-cre mice exhibited reduced food intake responses to fasting/refeeding and impaired regulation of BT when exposed to 15°C and 30°C ambient temperatures. Despite being obese and having many features of metabolic syndrome, Shp2/CamKIIα-cre mice had similar daily average BP and HR compared to Shp2flox/flox mice (112±2 vs 113±1 mmHg and 595±34 vs 650±40 bpm), but exhibited increased BP and HR responses to cold exposure and acute air-jet stress test. Leptin's ability to reduce food intake and to raise BP were markedly attenuated in Shp2/CamKIIα-cre mice. Conclusion These results suggest that forebrain Shp2 signaling regulates food intake, appetite responses to caloric deprivation, and thermogenic control of body temperature during variations in ambient temperature. Deficiency of Shp2 signaling in the forebrain is associated with augmented cardiovascular responses to cold and acute stress but attenuated BP responses to leptin.

Background We describe the background, rationale, intervention components, and formative results of a demonstration project aimed to ameliorate five socio-structural barriers to HIV services for young Black men aged 18-29 living with and at risk for HIV in Louisiana. Methods The interventions and activities consisted of (1) five person-centered approaches to enhance linkage to HIV services and improve socioeconomic outcomes; (2) the implementation of systematic mystery shopping tests to document instances of housing discrimination; (3) the development and implementation of a multi-prong communications campaign to increase knowledge about the signs of housing discrimination and community resources among young Black men who have sex with men (YBMSM); (4) the integration of HIV/STI services and lesbian, gay, bisexual, and trans (LGBT)-inclusive events on Historically Black Colleges and Universities (HBCUs); and (5) the development of a safe space for YBMSM. A multi-method approach was used to evaluate the outcomes of the different interventions. Results The majority (62%) of participants living with HIV were linked to HIV care and 49% had achieved viral suppression. More than 40% of participants were employed during the project. Thirty-seven percent (37%) of the mystery shopping tests showed definite or possible signs of housing discrimination. The housing campaign's duration was limited with unknown longterm impact among YBMSM. Fifteen cases of syphilis were identified during two HBCU events. A safe space was specifically created for YBMSM at a community-based organization. Conclusion Multi-component holistic health interventions are needed to improve HIV outcomes and curb the high HIV rates among young Black men, particularly YBMSM in the United States and the Deep South. Keywords Black men who have sex with men (BMSM). Social and structural factors. HIV prevention. South. Young Black men

Obesity is recognized as a major worldwide health problem. Excess weight gain is the most common cause of elevated blood pressure (BP) and markedly increases the risk of metabolic, cardiovascular and renal diseases. Although the mechanisms linking obesity with hypertension have not been fully elucidated, increased sympathetic nervous system (SNS) activity contributes to elevated BP in obese subjects. Recent evidence indicates that leptin and the central nervous system (CNS) melanocortin system, including melanocortin 4 receptors (MC4R), play a key role in linking obesity with increased SNS activity and hypertension. Leptin, a peptide-hormone produced by adipose tissue, crosses the blood–brain barrier and activates brain centers that control multiple metabolic functions as well as SNS activity and BP via the CNS melanocortin system. The crosstalk between peripheral signals (e.g., leptin) and activation of CNS pathways (e.g., MC4R) that regulate energy balance, SNS activity and BP represents an important target for treating obesity and its metabolic and cardiovascular consequences.

Our previous studies demonstrate an important role for the brain melanocortin system in regulating sympathetic nervous system activity and blood pressure (BP) as well as in modulating BP responses to stress. However, the brain regions involved in melanocortin‐4 receptors (MC4R)‐mediated modulation of cardiovascular responses to acute stress are unknown. In this study, we examined whether rescue of MC4R specifically in the paraventricular nucleus of the hypothalamus (PVN) or in the rostral ventrolateral medulla (RVLM) of whole‐body MC4R deficient mice (LoxTB‐MC4R mice) restores BP response to acute air‐jet stress. Using Cre‐loxP technology we selectively rescued MC4R in the PVN (LoxTB‐MC4R/Sim1, n=5) or RVLM (Cre‐RVLM/LoxTB‐MC4R mice, n=5). Mice were implanted with telemetry probes for measurement of mean arterial pressure (MAP). After a 10‐day recovery period, baseline MAP was measured for 3 consecutive days and during an acute air‐jet stress test. MAP was continuously measured for 30 minutes before, during and 30 minutes after the stress test. LoxTB‐MC4R mice were slightly heavier (53±2 vs 43±1 and 48±3 g), but had similar baseline MAP (109±1 vs 110±1 and 113±2 mmHg) compared to LoxTB‐MC4R/Sim1 and Cre‐RVLM/LoxTB‐MC4R mice. Acute air‐jet stress significantly increased MAP by 28±2 and 33±2 mmHg in loxTB‐MC4R/Sim1 and Cre‐RVLM/LoxTB‐MC4R compared to only 22±2 mmHg in loxTB‐MC4R mice. These results indicate that MC4Rs in PVN and RVLM neurons participate in the modulation of BP response to acute stress. (NHLBI‐PO1HL51971, NIGMS P20GM104357 and AHA SDG5680016) Grant Funding Source: AHA and NIH