Destigmatizing and Democratizing Postpartum Care: A "Black Woman-Person First" Approach.

Optimizing postpartum care highlights the need for care coordination, enhancement, and expansion of health care services after childbirth. Yet the prioritization of disease surveillance, management, and mitigation during birth and beyond within the American College of Obstetrics and Gynecology facilitates the medicalization and pathologization of Black bodies, voices, and power. Thus, we offer the Building and Bridging Black Futures Beyond Birth Model: A 12-Step Black Woman-Person First Approach, as a more humane and holistic model of culturally affirming and clinically responsive care. Destigmatizing and democratizing care bridges the gap between intent and impact in postpartum care optimization, particularly for Black women, girls, and gender expansive people and their communities.

An Angiotensin-Responsive Connection from the Lamina Terminalis to the Paraventricular Nucleus of the Hypothalamus Evokes Vasopressin Secretion to Increase Blood Pressure in Mice.

Blood pressure is controlled by endocrine, autonomic, and behavioral responses that maintain blood volume and perfusion pressure at levels optimal for survival. Although it is clear that central angiotensin type 1a receptors (AT1aR; encoded by the Agtr1a gene) influence these processes, the neuronal circuits mediating these effects are incompletely understood. The present studies characterize the structure and function of AT1aR neurons in the lamina terminalis (containing the median preoptic nucleus and organum vasculosum of the lamina terminalis), thereby evaluating their roles in blood pressure control. Using male Agtr1a-Cre mice, neuroanatomical studies reveal that AT1aR neurons in the area are largely glutamatergic and send projections to the paraventricular nucleus of the hypothalamus (PVN) that appear to synapse onto vasopressin-synthesizing neurons. To evaluate the functionality of these lamina terminalis AT1aR neurons, we virally delivered light-sensitive opsins and then optogenetically excited or inhibited the neurons while evaluating cardiovascular parameters or fluid intake. Optogenetic excitation robustly elevated blood pressure, water intake, and sodium intake, while optogenetic inhibition produced the opposite effects. Intriguingly, optogenetic excitation of these AT1aR neurons of the lamina terminalis also resulted in Fos induction in vasopressin neurons within the PVN and supraoptic nucleus. Further, within the PVN, selective optogenetic stimulation of afferents that arise from these lamina terminalis AT1aR neurons induced glutamate release onto magnocellular neurons and was sufficient to increase blood pressure. These cardiovascular effects were attenuated by systemic pretreatment with a vasopressin-1a-receptor antagonist. Collectively, these data indicate that excitation of lamina terminalis AT1aR neurons induces neuroendocrine and behavioral responses that increase blood pressure.SIGNIFICANCE STATEMENT Hypertension is a widespread health problem and risk factor for cardiovascular disease. Although treatments exist, a substantial percentage of patients suffer from "drug-resistant" hypertension, a condition associated with increased activation of brain angiotensin receptors, enhanced sympathetic nervous system activity, and elevated vasopressin levels. The present study highlights a role for angiotensin Type 1a receptor expressing neurons located within the lamina terminalis in regulating endocrine and behavioral responses that are involved in maintaining cardiovascular homeostasis. More specifically, data presented here reveal functional excitatory connections between angiotensin-sensitive neurons in the lamina terminals and vasopressin neurons in the paraventricular nucleus of the hypothalamus, and further indicate that activation of this circuit raises blood pressure. These neurons may be a promising target for antihypertensive therapeutics.

Community-informed models of perinatal and reproductive health services provision: A justice-centered paradigm toward equity among Black birthing communities.

Perinatal health outcomes in the United States continue to worsen, with the greatest burden of inequity falling on Black birthing communities. Despite transdisciplinary literature citing structural racism as a root cause of inequity, interventions continue to be mostly physician-centered models of perinatal and reproductive healthcare (PRH). These models prioritize individual, biomedical risk identification and stratification as solutions to achieving equity, without adequately addressing the social and structural determinants of health. The objective of this review is to: (1) examine the association between the impact of structural and obstetric racism and patient-centered access to PRH, (2) define and apply reproductive justice (RJ) as a framework to combat structural and obstetric racism in PRH, and (3) describe and demonstrate how to use an RJ lens to critically analyze physician-led and community-informed PRH models. We conclude with recommendations for building a PRH workforce whose capacity is aligned with racial equity. Institutional alignment with a RJ praxis creates opportunities for advancing PRH workforce diversification and development and improving PRH experiences and outcomes for our patients, communities, and workforce.

Fourth ventricular CART peptide induces c-fos in the area postrema and nucleus of the solitary tract via a CRF-receptor dependent mechanism.

Cocaine-and amphetamine-regulated transcript peptides (CARTp) suppress gastric emptying and nutritional intake following 4th icv administration. Whereas, the CARTp inhibition of gastric emptying was blocked by pre-treatment with a non-selective corticotropin releasing factor (CRF) antagonist, sucrose drinking was not, suggesting that CARTp- and CRF controls for food intake and gastric emptying are operated through separable dorsal hindbrain mechanisms. The aim of the study was to explore CARTp-CRF brainstem interactions on patterns of neuronal activation in areas of the brainstem and midbrain relevant to gastrointestinal control and feeding regulation. Rats received 4th icv injections of combinations of vehicle, CARTp (1µg), or the nonselective CRF antagonist, α-helical CRF9-41 (αCRF), in a randomized order. Brain sections were processed for c-fos by immunohistochemistry followed by image analysis at defined levels of the brain. CARTp (1µg, 4th icv) induced a robust c-fos response in the nucleus of the solitary tract (NTS) and area postrema (AP), whereas, no c-fos could be detected in the parabrachial nucleus (PBN), the paraventricular nucleus of the hypothalamus (PVN) or the arcuate nucleus of the hypothalamus (ARC). The c-fos expression in the structures of the dorsal vagal complex (DVC) was completely blocked by pre-treatment with the CRF antagonist, which did not by itself induce c-fos at any examined level. After CARTp and αCRF in combination, there was a tendency towards an increased c-fos response in the ARC. We conclude that CARTp activates cells of the area postrema and NTS via a downstream, CRF-dependent mechanism.

Central angiotensin II has catabolic action at white and brown adipose tissue.

Considerable evidence implicates the renin-angiotensin system (RAS) in the regulation of energy balance. To evaluate the role of the RAS in the central nervous system regulation of energy balance, we used osmotic minipumps to chronically administer angiotensin II (Ang II; icv; 0.7 ng/min for 24 days) to adult male Long-Evans rats, resulting in reduced food intake, body weight gain, and adiposity. The decrease in body weight and adiposity occurred relative to both ad libitum- and pair-fed controls, implying that reduced food intake in and of itself does not underlie all of these effects. Consistent with this, rats administered Ang II had increased whole body heat production and oxygen consumption. Additionally, chronic icv Ang II increased uncoupling protein-1 and ß(3)-adrenergic receptor expression in brown adipose tissue and ß3-adrenergic receptor expression in white adipose tissue, which is suggestive of enhanced sympathetic activation and thermogenesis. Chronic icv Ang II also increased hypothalamic agouti-related peptide and decreased hypothalamic proopiomelanocortin expression, consistent with a state of energy deficit. Moreover, chronic icv Ang II increased the anorectic corticotrophin- and thyroid-releasing hormones within the hypothalamus. These results suggest that Ang II acts in the brain to promote negative energy balance and that contributing mechanisms include an alteration in the hypothalamic circuits regulating energy balance, a decrease in food intake, an increase in energy expenditure, and an increase in sympathetic activation of brown and white adipose tissue.

Obesity/hyperleptinemic phenotype adversely affects hippocampal plasticity: effects of dietary restriction.

Epidemiological studies estimate that greater than 60% of the adult US population may be categorized as either overweight or obese and there is a growing appreciation that obesity affects the functional integrity of the central nervous system (CNS). We recently developed a lentivirus (LV) vector that produces an insulin receptor (IR) antisense RNA sequence (IRAS) that when injected into the hypothalamus selectively decreases IR signaling in hypothalamus, resulting in increased body weight, peripheral adiposity and plasma leptin levels. To test the hypothesis that this obesity/hyperleptinemic phenotype would impair hippocampal synaptic transmission, we examined short term potentiation (STP) and long term potentiation (LTP) in the hippocampus of rats that received the LV-IRAS construct or the LV-Control construct in the hypothalamus (hypo-IRAS and hypo-Con, respectively). Stimulation of the Schaffer collaterals elicits STP that develops into LTP in the CA1 region of hypo-Con rats; conversely, hypo-IRAS rats exhibit STP that fails to develop into LTP. To more closely examine the potential role of hyperleptinemia in these electrophysiological deficits, hypo-IRAS were subjected to mild food restriction paradigms that would either: 1) prevent the development of the obesity phenotype; or 2) reverse an established obesity phenotype in hypo-IRAS rats. Both of these paradigms restored LTP in the CA1 region and reversed the decreases in the phosphorylated/total ratio of GluA1 Ser845 AMPA receptor subunit expression observed in the hippocampus of hypo-IRAS rats. Collectively, these data support the hypothesis that obesity impairs hippocampal synaptic transmission and support the hypothesis that these deficits are mediated through the impairment of hippocampal leptin activity.

Meal patterns and hypothalamic NPY expression during chronic social stress and recovery.

In the present study, we examined meal patterns during and after exposure to the visible burrow system (VBS), a rodent model of chronic social stress, to determine how the microstructure of food intake relates to the metabolic consequences of social subordination. Male Long-Evans rats were housed in mixed-sex VBS colonies (4 male, 2 female) for 2 wk, during which time a dominance hierarchy formed [1 dominant male (DOM) and 3 subordinate males (SUB)], and then male rats were individually housed for a 3-wk recovery period. Controls were individually housed with females during the 2-wk VBS period and had no changes in ingestive behavior compared with a habituation period. During the hierarchy-formation phase of VBS housing, DOM and SUB had a reduced meal frequency, whereas SUB also had a reduced meal size. However, during the hierarchy-maintenance phase of VBS housing, DOM meal patterns did not differ from controls, whereas SUB continued to display a reduced food intake via less frequent meals. During recovery, DOM had comparable meal patterns to controls, whereas SUB had an increased meal size. Hypothalamic neuropeptide Y (NPY) mRNA levels were not different between these groups during the experimental period. Together, the results suggest that exposure to chronic social stress alters ingestive behavior both acutely and in the long term, which may influence the metabolic changes that accompany bouts of stress and recovery; however, these differences in meal patterns do not appear to be mediated by hypothalamic NPY.

Angiotensin type 1 receptors in the subfornical organ mediate the drinking and hypothalamic-pituitary-adrenal response to systemic isoproterenol.

Circulating angiotensin II (ANGII) elicits water intake and activates the hypothalamic-pituitary-adrenal (HPA) axis by stimulating angiotensin type 1 receptors (AT1Rs) within circumventricular organs. The subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT) are circumventricular organs that express AT1Rs that bind blood-borne ANGII and stimulate integrative and effector regions of the brain. The goal of these studies was to determine the contribution of AT1Rs within the SFO and OVLT to the water intake and HPA response to increased circulating ANGII. Antisense oligonucleotides directed against the AT1R [AT1R antisense (AT1R AS)] were administered into the OVLT or SFO. Quantitative receptor autoradiography confirmed that AT1R AS decreased ANGII binding in the SFO and OVLT compared with the scrambled sequence control but did not affect AT1R binding in other nuclei. Subsequently, water intake, ACTH, and corticosterone (CORT) were assessed after administration of isoproterenol, a beta-adrenergic agonist that decreases blood pressure and elevates circulating ANGII. Delivery of AT1R AS into the SFO attenuated water intake, ACTH, and CORT after isoproterenol, whereas similar treatment in the OVLT had no effect. To determine the specificity of this blunted drinking and HPA response, the same parameters were measured after treatment with hypertonic saline, a stimulus that induces drinking independently of ANGII. Delivery of AT1R AS into the SFO or OVLT had no effect on water intake, ACTH, or CORT after hypertonic saline. The results imply that AT1R within the SFO mediate drinking and HPA responses to stimuli that increase circulating ANGII.

Leptin activates hypothalamic acetyl-CoA carboxylase to inhibit food intake.

Hypothalamic fatty acid metabolism has recently been implicated in the controls of food intake and energy homeostasis. We report that intracerebroventricular (ICV) injection of leptin, concomitant with inhibiting AMP-activated kinase (AMPK), activates acetyl-CoA carboxylase (ACC), the key regulatory enzyme in fatty acid biosynthesis, in the arcuate nucleus (Arc) and paraventricular nucleus (PVN) in the hypothalamus. Arc overexpression of constitutively active AMPK prevents the Arc ACC activation in response to ICV leptin, supporting the hypothesis that AMPK lies upstream of ACC in leptin's Arc intracellular signaling pathway. Inhibiting hypothalamic ACC with 5-tetradecyloxy-2-furoic acid, a specific ACC inhibitor, blocks leptin-mediated decreases in food intake, body weight, and mRNA level of the orexigenic neuropeptide NPY. These results show that hypothalamic ACC activation makes an important contribution to leptin's anorectic effects. Furthermore, we find that ICV leptin up-regulates the level of malonyl-CoA (the intermediate of fatty acid biosynthesis) specifically in the Arc and increases the level of palmitoyl-CoA (a major product of fatty acid biosynthesis) specifically in the PVN. The rises of both levels are blocked by 5-tetradecyloxy-2-furoic acid along with the blockade of leptin-mediated hypophagia. These data suggest malonyl-CoA as a downstream mediator of ACC in leptin's signaling pathway in the Arc and imply that palmitoyl-CoA, instead of malonyl-CoA, could be an effector in relaying ACC signaling in the PVN. Together, these findings highlight site-specific impacts of hypothalamic ACC activation in leptin's anorectic signaling cascade.

Lateral ventricular ghrelin and fourth ventricular ghrelin induce similar increases in food intake and patterns of hypothalamic gene expression.

The gut peptide ghrelin has been shown to stimulate food intake after both peripheral and central administration, and the hypothalamic arcuate nucleus has been proposed to be the major site for mediating this feeding stimulatory action. Ghrelin receptors are widely distributed in the brain, and hindbrain ghrelin administration has been shown to potently stimulate feeding, suggesting that there may be other sites for ghrelin action. In the present study, we have further assessed potential sites for ghrelin action by comparing the ability of lateral and fourth ventricular ghrelin administration to stimulate food intake and alter patterns of hypothalamic gene expression. Ghrelin (0.32, 1, or 3.2 nmol) in the lateral or fourth ventricle significantly increased food intake in the first 4 h after injection, with no ventricle-dependent differences in degree or time course of hyperphagia. One nanomole of ghrelin into either the lateral or fourth ventricle resulted in similar increases in arcuate nucleus neuropeptide Y mRNA expression. Expression levels of agouti-related peptide or proopiomelanocortin mRNA were not affected by ghrelin administration. These data demonstrate that ghrelin can affect food intake and hypothalamic gene expression through interactions at multiple brain sites.

Altered hypothalamic signaling and responses to food deprivation in rats fed a low-carbohydrate diet.

OBJECTIVE: To model how consuming a low-carbohydrate (LC) diet influences food intake and body weight. RESEARCH METHODS AND PROCEDURES: Food intake and body weight were monitored in rats with access to chow (CH), LC-high-fat (HF), or HF diets. After 8 weeks, rats received intracerebroventricular injections of a melanocortin agonist (melanotan-II) and antagonist (SHU9119), and feeding responses were measured. At sacrifice, plasma hormones and hypothalamic expression of mRNA for proopiomelanocortin (POMC), melanocortin-4 receptor, neuropeptide Y (NPY), and agouti related protein (AgRP) were assessed. A second set of rats had access to diet (chow or LC-HF) for 4 weeks followed by 24 h food deprivation on two occasions, after which food intake and hypothalamic POMC, NPY, and AgRP mRNA expression were measured. RESULTS: HF rats consumed more food and gained more weight than rats on CH or LC-HF diets. Despite similar intakes and weight gains, LC-HF rats had increased adiposity relative to CH rats. LC-HF rats were more sensitive to melanotan-II and less sensitive to SHU9119. LC-HF rats had increased plasma leptin and ghrelin levels and decreased insulin levels, and patterns of NPY and POMC mRNA expression were consistent with those of food-deprived rats. LC-HF rats did not show rebound hyperphagia after food deprivation, and levels NPY, POMC, and AgRP mRNA expression were not affected by deprivation. DISCUSSION: Our results demonstrate that an LC diet influences multiple systems involved in the controls of food intake and body weight. These data also suggest that maintenance on an LC-HF diet affects food intake by reducing compensatory responses to food deprivation.

Running wheel activity prevents hyperphagia and obesity in Otsuka long-evans Tokushima Fatty rats: role of hypothalamic signaling.

Otsuka Long-Evans Tokushima fatty (OLETF) rats lacking cholecystokinin-A receptors are hyperphagic, obese, and diabetic. Although exercise attenuates OLETF rats' obesity, the mechanisms underlying the effects of exercise are unclear. In this study, we determined the effects of running wheel activity on patterns of body weight gain, food intake, and hypothalamic gene expression. We demonstrate that voluntary running activity beginning at 8 wk of age normalized meal patterns, food intake, body weight, and plasma levels of glucose and leptin in OLETF rats. During the initial exercise period, corticotropin-releasing factor (CRF) mRNA expression was significantly elevated in the dorsomedial hypothalamus (DMH) but not in the paraventricular nucleus in both OLETF and control Long-Evans Tokushima rats. In response to long-term exercise, arcuate nucleus (Arc) neuropeptide Y (NPY), and proopiomelanocortin as well as DMH NPY and CRF mRNA expression were increased in Long-Evans Tokushima rats. In contrast, whereas exercising OLETF rats had increased Arc NPY and DMH CRF expression, Arc proopiomelanocortin and DMH NPY mRNA levels were not elevated. Finally, we demonstrate that the effects of exercise on body weight in OLETF rats were long lasting. Although food intake and body weight were increased in OLETF rats when running wheels were locked, weights did not return to those of sedentary OLETF rats. Together, these data suggest that the elevation of DMH CRF expression may mediate the short-term feeding inhibitory effects of exercise and that exercise limits the elevation of DMH NPY expression to account for the overall prevention of OLETF rats' obesity.

Differential roles for cholecystokinin a receptors in energy balance in rats and mice.

Although cholecystokinin A (CCK-A) receptors (CCK-AR) mediate the feeding inhibitory actions of CCK in both rats and mice, the absence of CCK-AR results in species-specific phenotypes. The lack of CCK-AR in Otsuka Long-Evans Tokushima fatty (OLETF) rats results in hyperphagia and obesity. We have suggested that demonstrated increases in meal size and elevated levels of dorsomedial hypothalamic (DMH) neuropeptide Y (NPY) gene expression may contribute to this phenotype. In contrast to OLETF rats, CCK-AR(-/-) mice have normal total daily food intake and do not develop obesity. To assess the basis underlying the different phenotypes in rats and mice lacking CCK-AR, we characterized meal patterns in CCK-AR(-/-) mice and determined whether CCK-AR(-/-) mice exhibited an alteration in DMH NPY gene expression. We demonstrate that although CCK-AR(-/-) mice show a similar dysregulation in meal size as OLETF rats, they do not have an elevation in DMH NPY mRNA expression levels. In fact, intact mice have no CCK-AR in the DMH. Furthermore, in intact rats, NPY and CCK-AR are colocalized in DMH neurons, and parenchymal injection of CCK into the DMH reduces food intake and down-regulates DMH NPY mRNA expression. These results suggest that although CCK-AR plays a role in the mediation of CCK actions in the control of meal size in both rats and mice, CCK-AR seems to contribute to modulating DMH NPY levels only in rats. The deficit in CCK's action in the control of DMH NPY gene expression may play a major role in the obese phenotype in OLETF rats.