The Multi-faceted Profile of Corticotropin-releasing Factor (CRF) Family of Neuropeptides and of their Receptors on the Paracrine/Local Regulation of the Inflammatory Response.

BACKGROUND: The corticotropin releasing factor (CRF) family of neuropeptides, CRF and the Urocortins, and their receptors are present not only within the central nervous system but also in the periphery at various locations and at the sites of inflammation where they influence its progress in a complex local / paracrine manner. OBJECTIVE AND METHODS: This review summarizes current knowledge regarding the regulation of inflammatory process by CRF family of neuropeptides and receptors with a special sight into their role in inflammatory pain and in chronic low grade inflammation that occurs in obesity. For this purpose, we searched for relevant peer-reviewed research articles using bibliographic databases. RESULTS: The CRF neuropeptides are either produced locally, by components of the inflammatory response or they may reach the inflammation sites via postganglionic sympathetic and sensory afferent nerve transport. It now appears that most immune cells taking part in the inflammatory process express CRF receptor type 1 (CRF1R) and type 2 (CRF2R) and thus represent targets of CRF neuropeptides. Indeed, mast cells, monocytes / macrophages, neutrophils and other types of immune cells express both types of the CRF receptors. In addition to their role in the pathophysiology of inflammation, CRF and its receptors also exert modulatory effects on inflammatory pain. Finally, it now appears that the CRF system is also present in adipose tissue and may play a crucial role in the development of the chronic low grade inflammation, which is characteristic of obesity. CONCLUSION: The local effects of the CRF family of neuropeptides can be either pro- or antiinflammatory depending on concentration of each type of neuropeptide present and the ratio of the local expression of their receptors CRF1R and CRF2R.

Adiponectin levels may help assess the clinical repercussions of obesity irrespective of body mass index.

OBJECTIVE: Adiponectin is the major product of adipose tissue. The aim of this study was to associate adiponectin levels with adipose tissue and metabolic indices. DESIGN: Plasma samples of 274 non-diabetic volunteers were collected to evaluate for adiponectin, inflammatory markers, insulin and lipid parameters. Body fat composition was measured by DEXA. RESULTS: As expected, adiponectin levels correlated with body mass index (BMI) and gender but a wide scattering was evident. When the population was divided into two groups per median levels of adiponectin (11.94 µg/mL), adiponectin was correlated with various metabolic indices. Persons displaying relatively high adiponectin levels [17.7(CI:14.8-21.0]µg/mL; MEDIAN (25%-75%)] exhibited lower levels of inflammatory markers (hs-CRP, plasminogen, erythrocyte sedimentation rate), circulating lipids and markers of insulin sensitivity (fasting blood glucose, insulin, HbA1c and HOMA-IR) compared to those individuals displaying low-adiponectin levels [8.9(CI:6.9-10.6)µg/mL]. The percentage of high-adiponectin individuals decreased from 69.6% in the normal-BMI group to 36.5% in the obese-BMI group. Average adiponectin levels in the high-adiponectin normal-BMI group were significantly higher compared to the high-adiponectin obese-BMI group (p=0.014). Regarding body fat, only the individuals with high adiponectin levels in either the combined population or within the obese-BMI group displayed low levels of waist-to-hip ratio. Interestingly, high-adiponectin levels within the obese-BMI group were associated with higher legs fat than trunk fat as compared to the low-adiponectin obese-BMI group. CONCLUSIONS: Our data suggest that the distribution of adiponectin above or below a cutoff level may offer additional clinical information over and above that of BMI grouping regarding inflammatory profile, insulin-sensitivity and adiposity.

Muscular effects of vitamin D in young athletes and non-athletes and in the elderly.

Muscles are major targets of vitamin D. Exposure of skeletal muscles to vitamin D induces the expression of multiple myogenic transcription factors enhancing muscle cell proliferation and differentiation. At the same time vitamin D suppresses the expression of myostatin, a negative regulator of muscle mass. Moreover, vitamin D increases the number of type II or fast twitch muscle cells and in particular that of type IIA cells, while its deficiency causes type IIA cell atrophy. Furthermore, vitamin D supplementation in young males with low vitamin D levels increases the percentage of type IIA fibers in muscles, causing an increase in muscular high power output. Vitamin D levels are strongly associated with exercise performance in athletes and physically active individuals. In the elderly and in adults below the age of 65, several studies have established a close association between vitamin D levels and neuromuscular coordination. The aim of this review is to appraise our current understanding of the significance of vitamin D on muscular performance in both older and frail individuals as well as in younger adults, athletes or non-athletes with regard to both ordinary everyday musculoskeletal tasks and peak athletic performance.

The association between obesity and fluid intelligence impairment is mediated by chronic low-grade inflammation.

Published evidence suggests that obesity impairs cognition. Development of chronic low-grade inflammation (CLGI) represents the earliest consequence of obesity. The present study investigated the association between obesity and fluid intelligence impairment and assessed the potential mediating role of CLGI and psychological (depression/anxiety symptoms), lifestyle (exercise) and physiological (metabolic dysfunction indices) factors in this association. Clinically healthy participants (n 188), grouped as per BMI, underwent cognitive (General Ability Measure for Adults), psychological (Beck Depression Inventory-II and State-Trait Anxiety Inventory) and activity (Godin leisure-time physical activity) measurements. Biochemical parameters included the following: (a) indices of CLGI (high-sensitivity C-reactive protein, erythrocyte sedimentation rate and fibrinogen); (b) insulin resistance (Homeostasis Model Assessment of Insulin Resistance index); (c) adiposity (plasma adiponectin). An inverse association between elevated BMI and fluid intelligence was observed, with obese participants displaying significantly poorer performance compared with age-matched normal-weight peers. Structural equation modelling results were consistent with a negative impact of obesity on cognition that was mediated by CLGI. The results of the present study support the hypothesis that reduced general cognitive ability is associated with obesity, an adverse effect mainly mediated by obesity-associated activation of innate immunity.

Sex steroids and personality traits in the middle luteal phase of healthy normally menstruating young professional women.

OBJECTIVE: Sex steroids affect human behavior. The aim of the present study was to determine the associations, if any, between the circulating levels of gonadal and adrenal sex steroids in the mid luteal phase (21st day of a normal menstrual cycle, MC) of young professional women and psychometric parameters as assessed by the Minnesota Multiphasic Personality Inventory (MMPI). RESULTS: Our results are as follows: (a) The metabolic product of activated adrenal and gonadal androgens, 3alpha-diolG, was modestly but significantly associated with the social introversion scale (10-SI) (r=0.36, p<0.05), independently accounting for 13% of its variation across participants (R²=0.13, F(1,45)=6.58, p=0.014). (b) Total testosterone was significantly associated with the paranoia scale (6-Pa) (r=0.27, p<0.05). Multiple regression analyses indicated that 10% of the variability in paranoia scores could be independently explained by total testosterone levels (R²=0.10, F(1,57)=6.23, p=0.016). We were unable to find any association between the circulating androgens and scores on the masculinity-femininity scale (Mf). We were also unable to document any association between the weak adrenal androgens DHEA and DHEA-S and depression in contrast to several published reports. (c) Our data suggest a marginally significant association between progesterone and scores on the 7-Pt (obsessive/compulsive/psychasthenia) scale (r=0.27, p<0.05). However, only 7% of the 7-Pt variance was explained by progesterone (R²=0.071, F(1,50)=3.81, p=0.057). CONCLUSIONS: We have found that total testosterone was associated with the paranoia score, the metabolic product of activated androgens, 3alpha-diolG, to social introversion and, finally, progesterone to obsessive-compulsive behavior.