***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Neuroendocrine abnormalities , such as activation of the hypothalamic-pituitary-adrenal ( HPA ) axis , are associated with obesity ; however , few large-scale population -based studies have examined HPA axis and markers of obesity . We examined the cross-sectional association of the cortisol awakening response ( CAR ) and diurnal salivary cortisol curve with  obesity . The Multi-Ethnic Study of Atherosclerosis ( MESA ) Stress Study includes 1,002 White , Hispanic , and Black men and women ( mean age 65±9.8 years ) who collected up to 18 salivary cortisol sample s over 3 days . Cortisol profiles were modeled using regression spline models that incorporated r and om parameters for subject-specific effects . Cortisol curve measures included awakening cortisol , CAR ( awakening to 30 minutes post-awakening ) , early decline ( 30 minutes to 2 hours post-awakening ) , late decline ( 2 hours post-awakening to bedtime ) , and the corresponding areas under the curve ( AUC ) . Body-mass-index ( BMI ) and waist circumference ( WC ) were used to estimate adiposity . For the entire cohort , both BMI and WC were negatively correlated with awakening cortisol ( p<0.05 ) , AUC during awakening rise and early decline and positively correlated to the early decline slope ( p<0.05 ) after adjustments for age , race/ethnicity , gender , diabetes status , socioeconomic status , beta blockers , steroids , hormone replacement therapy and smoking status . No heterogeneities of effects were observed by gender , age , and race/ethnicity . Higher BMI and WC are associated with neuroendocrine dysregulation , which is present in a large population sample , and only partially explained by other covariates 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 st and ard laboratory stressor to examine HPA response to acute stress and underwent diurnal saliva sampling for basal cortisol and response to dexamethasone administration . Based on perceived stress scores , women were divided into extreme quartiles of low versus high stress categories . We found as hypothesized that the high stress group had significantly greater BMI and sagittal diameter , and reported greater emotional eating . In response to acute lab stressor , the high stress group showed a blunted cortisol response , lower diurnal cortisol levels , and greater suppression in response to dexamethasone . These cross-sectional findings support the animal model , which suggests that long-term adaptation to chronic stress in the face of dense calories result in greater visceral fat accumulation ( via ingestion of calorie-dense food ) , which in turn modulates HPA axis response , result ing in lower cortisol levels 11beta-Hydroxysteroid dehydrogenase type 1 ( 11HSD1 ) regenerates cortisol from cortisone within adipose tissue and liver . 11HSD1 inhibitors may enhance insulin sensitivity in type 2 diabetes and be most efficacious in obesity when 11HSD1 is increased in subcutaneous adipose biopsies . We examined the regeneration of cortisol in vivo in obesity , and the effects of the 11HSD1 inhibitor carbenoxolone . We compared six lean and six obese men and performed a r and omized , placebo-controlled crossover study of  carbenoxolone in obese men . The obese men had no difference in their whole-body rate of regenerating cortisol ( measured with 9,11,12,12-[(2)H(4)]cortisol tracer ) , but had more rapid conversion of [(3)H]cortisone to [(3)H]cortisol in abdominal subcutaneous adipose tissue ( measured with microdialysis ) . During insulin infusion , adipose 11HSD1 activity fell markedly in lean but not in obese men . Carbenoxolone inhibited whole-body cortisol regeneration , but did not significantly inhibit adipose 11HSD1 and had no effects on insulin sensitivity ( measured by [(2)H(2)]glucose infusion with or without hyperinsulinemia ) . Thus , in vivo cortisol generation is increased selectively within adipose tissue in obesity , perhaps reflecting resistance to insulin-mediated downregulation of 11HSD1 . However , obese men are less susceptible than lean men to the insulin-sensitizing effects of carbenoxolone . To be useful in obese patients , 11HSD1 inhibitors will need to inhibit the enzyme more effectively in adipose tissue Free cortisol measured in saliva has been shown to have the same diurnal rhythm as serum cortisol , one that typically declines rapidly throughout the waking day . A recent study showed that over 15 % of a sample of community individuals who were monitored over two days did not show the typical diurnal rhythm . The present study specifically tested the hypothesis that there is significant between-subject variation ( individual differences ) in diurnal rhythms using multi-level , r and om regression models . Analyses of participants from four studies were conducted ; studies varied in terms of the number of saliva sample s taken per day , the number of days studied , and participants ' demographic and health status . Significant individual differences of diurnal cycle in each of the four sample s were found . In at least 10 % of each sample no significant diurnal cycles was detected ; however , the overall mean level of cortisol of those with flat cycles differed among the sample s. These results suggest that some people do not have the expected diurnal rhythm of cortisol secretion . It is not clear what the determinants of this finding are or if there are any health consequences of having a flat cycle There is now evidence of a hypersensitive hypothalamo-pituitary-adrenal ( HPA ) axis in subjects with an elevated waist/hip circumference ratio ( WHR ) , an indicator of the central ization of body fat stores . The activity of the HPA axis is regulated by central glucocorticoid receptors , whose activity can be tested by the administration of exogenous glucocorticoids , which normally inhibit cortisol secretion . In this study , dexamethasone ( dex ) was administered in r and om order in doses of 0.05 , 0.125 , 0.25 and 0.5 mg at 10 p.m. with measurements of serum cortisol in the morning ( 8 a.m. ) of this and the following day . The test was performed on 22 apparently healthy men , 40 to 60 years of age , recruited from laboratory personnel , outpatient clinics or advertisements in a newspaper . Eight had a body mass index ( BMI ) ( kg/m2 ) of < 25 and 14 of > 25 . Twelve men had a waist hip ratio ( WHR ) of < 1.0 and 10 men had a WHR of > 1.0 . Cortisol values at baseline were correlated inversely with WHR and were usually lower in men with a high ( > 1.0 ) rather than a low than low ( < 1.0 ) WHR after dex inhibition . There was apparently no inhibition by dex at 0.05 and 0.125 mg on average in men with a WHR of > 1.0 . In addition , the inhibition at 0.5 mg dex correlated negatively with the WHR and was significantly lower ( p < 0.05 ) in men with a WHR of > 1.0 than in men with a WHR of < 1.0 . None of these differences or relationships was found to be dependent on BMI . It is concluded that men with an elevated WHR experience a decrease in the inhibition of cortisol secretion by dex . It is suggested that this could explain or contribute to the elevated sensitivity of their HPA axis . Furthermore , lower morning cortisol concentrations suggest a change in diurnal secretion patterns Increased hypothalamo-pituitary-adrenal axis drive has been reported in obese subjects but with paradoxically low or normal levels of plasma cortisol . Our current study was design ed to investigate whether glucocorticoid feedback was altered in obesity , both under basal and stressed conditions . Plasma ACTH and cortisol concentrations in male control or obese subjects ( age range 20 - 50 yr ) were measured at frequent intervals over 24 h during infusion of saline or hydrocortisone at two physiological doses ( 7.5 and 15 mg/d ) design ed to occupy predominantly mineralocorticoid rather than glucocorticoid receptors . The same subjects then underwent insulin-induced hypoglycemia either in the morning or the evening . Obese subjects had significantly higher basal ACTH and lower cortisol concentrations throughout the 24 h infusion period , compared with controls ( P < 0.05 , two-way ANOVA followed by Newman-Keuls posthoc analysis ) . Basal plasma ACTH was decreased in obese groups given low- or high-dose hydrocortisone during the day ( P < 0.05 ) but not during the night , unlike controls who responded to hydrocortisone both during the day and at night ( P < 0.05 ) . Obese subjects also showed resistance to steroid-induced inhibition of the ACTH response to hypoglycemia , compared with controls ( P < 0.05 ) . These data clearly show that obesity is associated with a relative insensitivity to glucocorticoid feedback , which is most marked during the night , and suggest that this condition is characterized by a decreased mineralocorticoid receptor response to circulating corticosteroids Introduction Similarities in the symptomatic expressions of excess adiposity and hypercortisolaemic conditions suggest that elevated glucocorticoid exposure may influence the pathogenesis of obesity . Circulating cortisol levels are not typically elevated in obese subjects , but data from large prospect i ve sample s are rare . We undertook an analysis to determine both cross‐sectional and longitudinal associations between body composition and serum cortisol concentrations in a r and omly chosen group of 999 community‐dwelling men , aged 40–79 years The aim of these analyses was to develop and describe easily implementable , yet information rich , approaches for analysis of the temporal profile of cortisol in human population s. A typical waking profile of cortisol in a sample of women aged 15 - 44 was parameterized by a piecewise linear regression model , implemented as a mixed model to accommo date repeated observations among individuals . The model was extended to distinguish characteristic cortisol profiles of obese women from those of non-obese women .  Sharp inflection points for the diurnal profile of cortisol were noted at 30 and 75 min past awakening . Obese women showed a slight tendency to have a less sharply rising and declining response to awakening than non-obese women Objective To investigate the relationships of blood pressure with carbohydrate metabolism , sympathetic activity and cortisol at different levels of body mass index in middle-aged men . Methods Cross-sectional data concerning men studied in the Paris Prospect i ve Study I were analysed . The cohort included 6424 subjects aged 40 - 53 years at entry , who were not being treated for hypertension or diabetes and had no overt heart disease . The parameters analysed were  glucose , insulin and free fatty acids levels , all assessed during fasting by the subject and 2h after a 75 g glucose load , resting heart rate and morning plasma cortisol levels Results Subjects with systolic blood pressure > 160mmHg had significantly higher glucose concentrations at any body mass index level whereas the difference in insulin levels between the subjects with and without high systolic blood pressure increased with body mass index . Heart rate , free fatty acids level and cortisol level were significantly higher in men with high systolic blood pressure . However , these parameters showed significant decreasing trends with body mass index . In normotensives , no such trends were observed . When analysing data according to diastolic blood pressure , the limit being 95mmHg , similar results were obtained for glucose and insulin levels , but no trend in heart rate , free fatty acids level and cortisol level with the body mass index level was statistically significant . Conclusions Mean glucose concentrations are higher in hypertensive men at all body mass index levels , whereas relative hyperinsulinaemia is present only in the more corpulent hypertensives . Heart rate , free fatty acids level and morning plasma cortisol level are elevated in hypertensive subjects at any body mass index level , but particularly in the lean ones with high systolic blood pressure Salivary Cortisol concentration was found to be directly proportional to the serum unbound Cortisol concentration both in normal men and women and in women with elevated cortisol-binding globulin ( CBG ) . The correlation was excellent in dynamic tests of adrenal function ( dexamethasone suppression , ACTH stimulation ) , in normals and patients with adrenal insufficiency , in tests of circadian variation and r and omly collected sample s. Women in the third trimester of normal pregnancy exhibited elevated salivary Cortisol throughout the day . The relationship between salivary and serum total Cortisol concentration was markedly non-linear with a more rapid increase in salivary concentration once the serum CBG was saturated . The rate of equilibrium of Cortisol between blood and saliva was very fast , being much less than 5 minutes . These data , combined with a simple , stress-free , non-invasive collection procedure , lead us to suggest that salivary Cortisol is a more appropriate measure for the clinical assessment of adrenocortical function than is serum Cortisol There is increasing evidence that the abdominal 
    Output:
    
RESULTS A general pattern of findings emerged where greater abdominal fat is associated with greater responsivity of the HPA axis , reflected in morning awakening and acute stress reactivity , but some studies did show underresponsiveness .
When examined in adipocytes , there is a clear upregulation of cortisol output ( due to greater expression of 11β-HSD1 ) , but in hepatic tissue this cortisol is downregulated .
Overall obesity ( BMI ) appears to also be related to a hyperresponsive HPA axis in many but not all studies , such as when acute reactivity is examined .