Novel Interventions to Reduce Stress and Overeating in Overweight Pregnant Women: A Feasibility Study.

Background High stress and depression during pregnancy are risk factors for worsened health trajectories for both mother and offspring. This is also true for pre-pregnancy obesity and excessive gestational weight gain. Reducing stress and depression may be one path to prevent excessive caloric intake and gestational weight gain.

Environmental enrichment alters splenic immune cell composition and enhances secondary influenza vaccine responses in mice.

Chronic stress has deleterious effects on immune function, which can lead to adverse health outcomes. However, studies investigating the impact of stress reduction interventions on immunity in clinical research have yielded divergent results, potentially stemming from differences in study design and genetic heterogeneity, among other clinical research challenges. To test the hypothesis that reducing glucocorticoid levels enhances certain immune functions, we administered influenza vaccine once (prime) or twice (boost) to mice housed in either standard control caging or environmental enrichment (EE) caging.

The calm mouse: an animal model of stress reduction.

Chronic stress is associated with negative health outcomes and is linked with neuroendocrine changes, deleterious effects on innate and adaptive immunity, and central nervous system neuropathology. Although stress management is commonly advocated clinically, there is insufficient mechanistic understanding of how decreasing stress affects disease pathogenesis. Therefore, we have developed a "calm mouse model" with caging enhancements designed to reduce murine stress.

Comfort food is comforting to those most stressed: evidence of the chronic stress response network in high stress women.

Chronically stressed rodents who are allowed to eat calorie-dense "comfort" food develop greater mesenteric fat, which in turn dampens hypothalamic-pituitary-adrenocortical (HPA) axis activity. We tested whether similar relations exist in humans, at least cross-sectionally. Fifty-nine healthy premenopausal women were exposed to a standard laboratory stressor to examine HPA response to acute stress and underwent diurnal saliva sampling for basal cortisol and response to dexamethasone administration.

Gonadotropin-releasing hormone fibers contact POMC neurons in the hypothalamic arcuate nucleus.

The metabolic state has long been shown to affect reproduction. Peripheral signals and hormones from the reproductive organs are also known to regulate energy metabolism and feeding and energy expenditure. Much attention has been paid to determine the signaling flow from key hypothalamic neuronal populations, including those producing the anorexigenic proopiomelanocortin (POMC) derivate, α-melanocyte stimulating hormone (α-MSH), to the medial preoptic area gonadotropin-releasing hormone (GnRH) neurons, cells that are the drivers of ovulation and reproduction in general.

Rapid alteration of stress-induced hypothalamic-pituitary-adrenal hormone secretion in the rat: a comparison of glucocorticoids and cannabinoids.

The hypothalamic-pituitary-adrenal (HPA) axis self-regulates through a glucocorticoid negative feedback mechanism that is stereotypically slow and long lasting. Rapid (seconds to minutes) glucocorticoid feedback, however, inhibits stress-induced adrenocorticotropic hormone (ACTH) secretion too quickly to result from classic transcriptional effects of the occupied glucocorticoid receptor. Cannabinoids may act as rapid intermediary messengers between glucocorticoids and HPA activation via retroactive inhibition of afferent glutamate stimulation of the corticotropin-releasing factor neurons in the paraventricular nucleus.

Stress-induced obesity and the emotional nervous system.

Stress and emotional brain networks foster eating behaviors that can lead to obesity. The neural networks underlying the complex interactions among stressors, body, brain and food intake are now better understood. Stressors, by activating a neural stress-response network, bias cognition toward increased emotional activity and degraded executive function.

Disengaging insulin from corticosterone: roles of each on energy intake and disposition.

Corticosterone and insulin play complex roles in the amount and composition of calories ingested, and the utilization and deposition of this energy. Understanding the interplay of these two hormones is complicated because increasing concentrations of corticosterone dose-dependently increase circulating insulin levels. We addressed individual contributions of each hormone by controlling, at steady-state levels, corticosterone (by adrenalectomy and exogenous replacement) and insulin (by streptozotocin-induced destruction of pancreatic beta-cells and exogenous replacement) across a spectrum of concentrations in rats, creating 8 hormonal combinations.

Metabolic and neuroendocrine consequences of a duodenal-jejunal bypass in rats on a choice diet.

Objective: We sought to examine insulin-sensitive food intake behavior and neuroendocrine and metabolic variables of rats that had undergone a duodenal-jejunal bypass (DJB).

Summary Of Background Data: A DJB that circumvents the duodenum and proximal jejunum while leaving the stomach unperturbed rapidly improves insulin sensitivity in type 2 diabetic rats. This segment of proximal small intestine is innervated by the gastroduodenal branch of the vagus nerve, the transection of which influences food intake choices in streptozotocin-diabetic rats.

An unexpected reduction in sucrose concentration activates the HPA axis on successive post shift days without attenuation by discriminative contextual stimuli.

Previous studies have shown that the successive negative contrast procedure, in which food-restricted rats entrained to once daily, brief presentations of 32% sucrose are unexpectedly shifted to a 4% solution, results in an adrenocortical response on the second, but not the first postshift day. We attempted to generalize that finding in our own procedure. In Experiment 1, two groups of rats were given a 32% sucrose solution once daily in their home cages for 14 days before being shifted to a 4% solution.

Palatable foods, stress, and energy stores sculpt corticotropin-releasing factor, adrenocorticotropin, and corticosterone concentrations after restraint.

Previous studies have shown reduced hypothalamo-pituitary-adrenal responses to both acute and chronic restraint stressors in rats allowed to ingest highly palatable foods (32% sucrose +/- lard) prior to restraint. In this study we tested the effects of prior access (7 d) to chow-only, sucrose/chow, lard/chow, or sucrose/lard/chow diets on central corticotropin-releasing factor (CRF) expression in rats studied in two experiments, 15 and 240 min after onset of restraint. Fat depot, particularly intraabdominal fat, weights were increased by prior access to palatable food, and circulating leptin concentrations were elevated in all groups.

Insulin and the constituent branches of the hepatic vagus interact to modulate hypothalamic and limbic neuropeptide mRNA expression differentially.

Insulin and signalling through the vagus nerve act in concert to regulate metabolic homeostasis and ingestive behaviour. Our previous studies using streptozotocin (STZ)-diabetic rats have shown that hepatic branch vagotomy (HV), gastroduodenal branch vagotomy (GV) and capsaicin treatment of the common hepatic branch that selectively destroys afferent fibres (CapV), all promote lard, but not total, caloric intake to levels similar to those achieved with insulin treatment. Because hypothalamic and limbic mRNA expression of neuropeptides linked to energy balance is altered by STZ-diabetes and HV, we examined the role(s) of insulin and the common hepatic and gastroduodenal branches of the vagus nerve and hepatic afferent fibres in the regulation of these neuropeptides in rats with high, steady-state corticosterone levels.

Lesions of the medial prefrontal cortex enhance the early phase of psychogenic fever to unexpected sucrose concentration reductions, promote recovery from negative contrast and enhance spontaneous recovery of sucrose-entrained anticipatory activity.

Two groups of rats, one bearing bilateral excitotoxic lesions of the medial prefrontal cortex (mPFC) and one sham-lesioned group, were run in a successive negative contrast paradigm. Both groups had telemeters implanted to monitor core temperature and activity. After ad libitum baseline and food restriction to 85% body weights, rats received a sucrose solution once daily for 5 min and 30 s at 10:30 h.

The gastroduodenal branch of the common hepatic vagus regulates voluntary lard intake, fat deposition, and plasma metabolites in streptozotocin-diabetic rats.

The common hepatic branch of the vagus nerve negatively regulates lard intake in rats with streptozotocin (STZ)-induced, insulin-dependent diabetes. However, this branch consists of two subbranches: the hepatic branch proper, which serves the liver, and the gastroduodenal branch, which serves the distal stomach, pancreas, and duodenum. The aim of this study was to determine whether the gastroduodenal branch specifically regulates voluntary lard intake.

Mapping brain c-Fos immunoreactivity after insulin-induced voluntary lard intake: insulin- and lard-associated patterns.

In addition to the inhibitory role of central insulin on food intake, insulin also acts to promote lard intake. We investigated the neural pathways involved in this facet of insulin action. Insulin or saline was infused into either the superior mesenteric or right external jugular veins of streptozotocin-diabetic rodents with elevated steady-state circulating corticosterone concentrations.

Temperature and activity responses to sucrose concentration reductions occur on the 1st but not the 2nd day of concentration shifts, and are blocked by low, constant glucocorticoids.

Previous findings (N. Pecoraro, J. Chou-Green, & M.

Afferent signalling through the common hepatic branch of the vagus inhibits voluntary lard intake and modifies plasma metabolite levels in rats.

The common hepatic branch of the vagus nerve is a two-way highway of communication between the brain and the liver, duodenum, stomach and pancreas that regulates many aspects of food intake and metabolism. In this study, we utilized the afferent-specific neurotoxin capsaicin to examine if common hepatic vagal sensory afferents regulate lard intake. Rats implanted with a corticosterone pellet were made diabetic using streptozotocin (STZ) and a subset received steady-state exogenous insulin replacement into the superior mesenteric vein.

Glucocorticoids and insulin both modulate caloric intake through actions on the brain.

Glucocorticoids act primarily in a feed-forward fashion on brain to activate CNS pathways that implement wanting appropriate to physiological needs. Thus, depending on the available conditions, elevated glucocorticoids may augment the behavioural want to run, fight or feed. Although glucocorticoids stimulate intake of chow, fat and sucrose, insulin appears to sculpt calorie-associated desires toward foods high in fat, acting through hepatic branch afferents of the vagus nerve.

Glucocorticoids, the etiology of obesity and the metabolic syndrome.

In mammals, glucocorticoid actions appear to have evolved to maintain and enhance energy stores to be used for life-saving gluconeogenesis. They act on the brain to stimulate search behaviors, palatable feeding and emotionally relevant memories, and they act on the body to mobilize stored peripheral energy and direct it to central depots that serve the substrate needs of the liver. Our work in rats shows that searching and intake of palatable foods (sucrose, saccharin and lard) are stimulated by corticosterone in a dose-related fashion.

Hepatic branch vagotomy, like insulin replacement, promotes voluntary lard intake in streptozotocin-diabetic rats.

Although high insulin concentrations reduce food intake, low insulin concentrations promote lard intake over chow, possibly via an insulin-derived, liver-mediated signal. To investigate the role of the hepatic vagus in voluntary lard intake, streptozotocin-diabetic rats with insulin or vehicle replaced into either the superior mesenteric or jugular veins received a hepatic branch vagotomy (HV) or a sham operation. All rats received a pellet of corticosterone that clamped the circulating steroid at moderately high concentrations to enhance lard intake.

Causes of obesity: looking beyond the hypothalamus.

The brain takes a primary position in the organism. We present the novel view that the brain gives priority to controlling its own adenosine triphosphate (ATP) concentration. It fulfils this tenet by orchestrating metabolism in the organism.

From Malthus to motive: how the HPA axis engineers the phenotype, yoking needs to wants.

The hypothalamo-pituitary-adrenal (HPA) axis is the critical mediator of the vertebrate stress response system, responding to environmental stressors by maintaining internal homeostasis and coupling the needs of the body to the wants of the mind. The HPA axis has numerous complex drivers and highly flexible operating characterisitics. Major drivers include two circadian drivers, two extra-hypothalamic networks controlling top-down (psychogenic) and bottom-up (systemic) threats, and two intra-hypothalamic networks coordinating behavioral, autonomic, and neuroendocrine outflows.