Hypothalamic integration of immune function and metabolism

Guijarro, Ana; Laviano, Alessandro; Meguid, Michael M.

doi:10.1016/s0079-6123(06)53022-5

Cited by 74 publications

(63 citation statements)

References 229 publications

(239 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In any event, our present results are compatible with a suppressed kisspeptin tone, originating from the ARC, at the acute phase of inflammation, which may be mechanistically relevant for the state of hypogonadotropic (low LH) hypogonadism (low T) observed at this period. As expected, on the basis of previous studies (2,9,24), our regimen of LPS administration resulted in a transient suppression of daily food intake and a concomitant reduction of body weight. LPS-induced anorexia is thought to be mediated mainly by different proinflammatory cytokines, which act on the hypothalamic networks controlling appetite (2).…”

Section: Discussionsupporting

confidence: 87%

Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects

Castellano

Bentsen

Martín‐Romero

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Tena-Sempere M. Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects. Am J Physiol Endocrinol Metab 299: E54 -E61, 2010. First published April 20, 2010 doi:10.1152/ajpendo.00081.2010.-Severe inflammatory challenges are frequently coupled to decreased food intake and disruption of reproductive function, the latter via deregulation of different signaling pathways that impinge onto GnRH neurons. Recently, the hypothalamic Kiss1 system, a major gatekeeper of GnRH function, was suggested as potential target for transmitting immune-mediated repression of the gonadotropic axis during acute inflammation, and yet key facets of such a phenomenon remain ill defined. Using lipopolysaccharide S (LPS)-treated male rats as model of inflammation, we document herein the pattern of hypothalamic kisspeptin immunoreactivity (IR) and hormonal responses to kisspeptin during the acute inflammatory phase. LPS injections induced a dramatic but transient drop of serum LH and testosterone levels. Suppression of gonadotropic function was associated with a significant decrease in kisspeptin-IR in the arcuate nucleus (ARC) that was not observed under conditions of metabolic stress induced by 48-h fasting. In addition, absolute responses to kisspeptin-10 (Kp-10), in terms of LH and testosterone secretion, were significantly attenuated in LPS-treated males that also displayed a decrease in food intake and body weight. Yet pair-fed males did not show similar alterations in LH and testosterone secretory responses to Kp-10, whose magnitude was preserved, if not augmented, during food restriction. In summary, our data document the impact of acute inflammation on kisspeptin content at the ARC as key center for the neuroendocrine control of reproduction. Our results also suggest that suppressed gonadotropic function following inflammatory challenges might involve a reduction in absolute responsiveness to kisspeptin that is independent of the anorectic effects of inflammation.Kiss1/kisspeptins; gonadotropin-releasing hormone; gonadotropins; lipopolysaccharide S IMMUNE/INFLAMMATORY CHALLENGES, such as those associated with severe bacterial infections, are commonly coupled with transient suppression of dispensable functions for individual survival, such as reproduction. Among a plethora of biological responses, administration of lipopolysaccharide S (LPS), a glycolipid of gram-negative bacteria, has been shown to disrupt puberty onset and gonadotropic function through deregulation of an array of signaling pathways, including different proinflammatory cytokines (IL-1, IL-6, TNF␣), growth factors, neurotransmitters (catecholamines, ␥-aminobutyric acid), and neuropeptides (corticotropin-releasing factor, arginine vasopressin, opioids) (1,10,16,28,33,35,37,39). However, although compelling evidence suggests that the above factors are variably involved in the suppression of the gonadotropinreleasing hormone (GnRH)/LH system by bacterial endotoxin (37,...

show abstract

Section: Discussionsupporting

confidence: 87%

Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects

Castellano

Bentsen

Martín‐Romero

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…This study provides molecular evidence that sleep deprivation suppresses IL-1-dependent pathways that trigger inflammation in the periphery and hypothalamus, an important area in the brain that regulates the acute phase response to infection (Blatteis, 1988;Guijarro et al, 2006).…”

Section: Discussionmentioning

confidence: 80%

Sleep deprivation attenuates endotoxin-induced cytokine gene expression independent of day length and circulating cortisol in male Siberian hamsters (Phodopus sungorus)

Ashley

Walton

Haim

et al. 2013

Journal of Experimental Biology

View full text Add to dashboard Cite

SUMMARYSleep is restorative, whereas reduced sleep leads to negative health outcomes, such as increased susceptibility to disease. Sleep deprivation tends to attenuate inflammatory responses triggered by infection or exposure to endotoxin, such as bacterial lipopolysaccharide (LPS). Previous studies have demonstrated that Siberian hamsters (Phodopus sungorus), photoperiodic rodents, attenuate LPS-induced fever, sickness behavior and upstream pro-inflammatory gene expression when adapted to short day lengths. Here, we tested whether manipulation of photoperiod alters the suppressive effects of sleep deprivation upon cytokine gene expression after LPS challenge. Male Siberian hamsters were adapted to long (16h:8h light:dark) or short (8h:16h light:dark) photoperiods for >10weeks, and were deprived of sleep for 24h using the multiple platform method or remained in their home cage. Hamsters received an intraperitoneal injection of LPS or saline (control) 18h after starting the protocol, and were killed 6h later. LPS increased liver and hypothalamic interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF) gene expression compared with vehicle. Among LPS-challenged hamsters, sleep deprivation reduced IL-1 mRNA levels in liver and hypothalamus, but not TNF. IL-1 attenuation was independent of circulating baseline cortisol, which did not increase after sleep deprivation. Conversely, photoperiod altered baseline cortisol, but not pro-inflammatory gene expression in sleep-deprived hamsters. These results suggest that neither photoperiod nor glucocorticoids influence the suppressive effect of sleep deprivation upon LPSinduced inflammation.

show abstract

“…The role of the hypothalamus in integrating immune function and metabolism is well recognized (26). Therefore, it should be considered as a key anatomical area, adapting behavior and peripheral metabolism to perceived challenges.…”

Section: Autonomic Nervous Systemmentioning

confidence: 99%

Neural control of the anorexia-cachexia syndrome

Laviano¹,

Inui²,

Marks³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

111

View full text Add to dashboard Cite

cachexia syndrome is a debilitating clinical condition characterizing the course of chronic diseases, which heavily impacts on patients' morbidity and quality of life, ultimately accelerating death. The pathogenesis is multifactorial and reflects the complexity and redundancy of the mechanisms controlling energy homeostasis under physiological conditions. Accumulating evidence indicates that, during disease, disturbances of the hypothalamic pathways controlling energy homeostasis occur, leading to profound metabolic changes in peripheral tissues. In particular, the hypothalamic melanocortin system does not respond appropriately to peripheral inputs, and its activity is diverted largely toward the promotion of catabolic stimuli (i.e., reduced energy intake, increased energy expenditure, possibly increased muscle proteolysis, and adipose tissue loss). Hypothalamic proinflammatory cytokines and serotonin, among other factors, are key in triggering hypothalamic resistance. These catabolic effects represent the central response to peripheral challenges (i.e., growing tumor, renal, cardiac failure, disrupted hepatic metabolism) that are likely sensed by the brain through the vagus nerve. Also, disease-induced changes in fatty acid oxidation within hypothalamic neurons may contribute to the dysfunction of the hypothalamic melanocortin system. Ultimately, sympathetic outflow mediates, at least in part, the metabolic changes in peripheral tissues. Other factors are likely involved in the pathogenesis of the anorexia-cachexia syndrome, and their role is currently being elucidated. However, available evidence shows that the constellation of symptoms characterizing this syndrome should be considered, at least in part, as different phenotypes of common neurochemical/metabolic alterations in the presence of a chronic inflammatory state. melanocortin; cytokines; serotonin; malonyl-coenzyme A; vagus nerve; sympathetic output THE ANOREXIA-CACHEXIA SYNDROME is a debilitating condition characterizing the clinical journey of patients suffering from chronic diseases including cancer, chronic obstructive pulmonary disease, tuberculosis, chronic heart failure, and end-stage renal insufficiency (64). As an experimental model, it represents a reliable and unique tool for the investigation of the mechanisms regulating energy intake and homeostasis. Beyond its relevance to human physiology, this syndrome impacts on clinical practice since it is highly prevalent and negatively influences patients' morbidity, mortality (66), and quality of life (57).The anorexia-cachexia syndrome is clinically characterized by a number of signs and symptoms interfering with energy intake (i.e., reduced appetite, early satiety, changes in taste/ smell) and affecting nutritional status (i.e., increased metabolic rate, weight loss, hormonal alterations, muscle and adipose tissue wasting, functional impairment, fatigue). At the biochemical and molecular levels, the main features of the anorexia-cachexia syndrome are the profound alterations of brain neurochemis...

show abstract

Hypothalamic integration of immune function and metabolism

Cited by 74 publications

References 229 publications

Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects

Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects

Sleep deprivation attenuates endotoxin-induced cytokine gene expression independent of day length and circulating cortisol in male Siberian hamsters (Phodopus sungorus)

Neural control of the anorexia-cachexia syndrome

Contact Info

Product

Resources

About