The effects of adrenal corticosteroids on subsequent adrenocorticotropin secretion are complex. Acutely (within hours), glucocorticoids (GCs) directly inhibit further activity in the hypothalamopituitary-adrenal axis, but the chronic actions (across days) of these steroids on brain are directly excitatory. Chronically high concentrations of GCs act in three ways that are functionally congruent. (i) GCs increase the expression of corticotropin-releasing factor (CRF) mRNA in the central nucleus of the amygdala, a critical node in the emotional brain. CRF enables recruitment of a chronic stress-response network. (ii) GCs increase the salience of pleasurable or compulsive activities (ingesting sucrose, fat, and drugs, or wheel-running). This motivates ingestion of ''comfort food.'' (iii) GCs act systemically to increase abdominal fat depots. This allows an increased signal of abdominal energy stores to inhibit catecholamines in the brainstem and CRF expression in hypothalamic neurons regulating adrenocorticotropin. Chronic stress, together with high GC concentrations, usually decreases body weight gain in rats; by contrast, in stressed or depressed humans chronic stress induces either increased comfort food intake and body weight gain or decreased intake and body weight loss. Comfort food ingestion that produces abdominal obesity, decreases CRF mRNA in the hypothalamus of rats. Depressed people who overeat have decreased cerebrospinal CRF, catecholamine concentrations, and hypothalamo-pituitary-adrenal activity. We propose that people eat comfort food in an attempt to reduce the activity in the chronic stress-response network with its attendant anxiety. These mechanisms, determined in rats, may explain some of the epidemic of obesity occurring in our society.corticotropin-releasing factor ͉ glucocorticoids ͉ high fat ͉ sucrose ͉ motivation O ur understanding of regulation of function in the hypothalamo-pituitary-adrenal (HPA) axis has changed profoundly in the last decades. The discovery of functions of the distributed cell groups of corticotropin-releasing factor (CRF) neurons, the motor neurons for activation of the pituitary and adrenal, as well as the tight interrelationships between calories, body weight, energy stores, and the HPA axis have occasioned revisions in our thinking. The upshot is a new working model, the output of which is modifiable through manipulation of caloric input (Fig. 1). The long-term consequences of such output modification in chronically stressed individuals may include deleterious weight gain, abdominal obesity, type II diabetes, increased cardiovascular morbidity, and mortality. We arrived at this model through interpretation of the results from studies on manipulation of energy balance, central CRF, and the effects of acute and chronic stress and glucocorticoid (GC) treatment in intact and adrenalectomized rats. GC Effects on HPA Function: Acute and ChronicCanonical GC-feedback inhibition of subsequent adrenocorticotropin (ACTH) secretion is easily demonstrated acutely, within the fi...

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ObjectiveTo determine whether adding mindfulness‐based eating and stress management practices to a diet‐exercise program improves weight loss and metabolic syndrome components.MethodsIn this study 194 adults with obesity were randomized to a 5.5‐month program with or without mindfulness training and identical diet‐exercise guidelines. Intention‐to‐treat analyses with multiple imputation were used for missing data. The primary outcome was 18‐month weight change.ResultsEstimated effects comparing the mindfulness to control arm favored the mindfulness arm in (a) weight loss at 12 months, −1.9 kg (95% CI: −4.5, 0.8; P = 0.17), and 18 months, −1.7 kg (95% CI: −4.7, 1.2; P = 0.24), though not statistically significant; (b) changes in fasting glucose at 12 months, −3.1 mg/dl (95% CI: −6.3, 0.1; P = 0.06), and 18 months, −4.1 mg/dl (95% CI: −7.3, −0.9; P = 0.01); and (c) changes in triglyceride/HDL ratio at 12 months, −0.57 (95% CI: −0.95, −0.18; P = 0.004), and 18 months, −0.36 (95% CI: −0.74, 0.03; P = 0.07). Estimates for other metabolic risk factors were not statistically significant, including waist circumference, blood pressure, and C‐reactive protein.ConclusionsMindfulness enhancements to a diet‐exercise program did not show substantial weight loss benefit but may promote long‐term improvement in some aspects of metabolic health in obesity that requires further study.