Jvalini Dwarkasing

Inhibition of COX-2-mediated eicosanoid production plays a major role in the anti-inflammatory effects of the endocannabinoid N-docosahexaenoylethanolamine (DHEA) in macrophages.

N‐docosahexaenoylethanolamine (DHEA) is the ethanolamine conjugate of the long‐chain polyunsaturated n‐3 fatty acid docosahexaenoic (DHA; 22: 6n‐3). Its concentration in animal tissues and human plasma increases when diets rich in fish or krill oil are consumed. DHEA displays anti‐inflammatory properties in vitro and was found to be released during an inflammatory response in mice. Here, we further examine possible targets involved in the immune‐modulating effects of DHEA.

Differences in food intake of tumour‐bearing cachectic mice are associated with hypothalamic serotonin signalling

Anorexia is a common symptom among cancer patients and contributes to malnutrition and strongly impinges on quality of life. Cancer‐induced anorexia is thought to be caused by an inability of food intake‐regulating systems in the hypothalamus to respond adequately to negative energy balance during tumour growth. Here, we show that this impaired response of food‐intake control is likely to be mediated by altered serotonin signalling and by failure in post‐transcriptional neuropeptide Y (NPY) regulation.

Hypothalamic inflammation and food intake regulation during chronic illness.

Anorexia is a common symptom in chronic illness. It contributes to malnutrition and strongly affects survival and quality of life. A common denominator of many chronic diseases is an elevated inflammatory status, which is considered to play a pivotal role in the failure of food-intake regulating systems in the hypothalamus. In this review, we summarize findings on the role of hypothalamic inflammation on food intake regulation involving hypothalamic neuropeptide Y (NPY) and pro-opiomelanocortin (POMC). Furthermore, we outline the role of serotonin in the inability of these peptide based food-intake regulating systems to respond and adapt to changes in energy metabolism during chronic disease.

Behavioural changes are a major contributing factor in the reduction of sarcopenia in caloric-restricted ageing mice

In rodent models, caloric restriction (CR) with maintenance of adequate micronutrient supply has been reported to increase lifespan and to reduce age‐induced muscle loss (sarcopenia) during ageing. In the present study, we further investigated effects of CR on the onset and severity of sarcopenia in ageing male C57BL/6 J mice. The aim of this study was to investigate whether CR induces changes in behaviour of the animals that could contribute to the pronounced health‐promoting effects of CR in rodents. In addition, we aimed to investigate in more detail the effects of CR on the onset and severity of sarcopenia.

The role of hypothalamic inflammation, the hypothalamic–pituitary–adrenal axis and serotonin in the cancer anorexia–cachexia syndrome

Purpose of review In cancer patients, the development of cachexia (muscle wasting) is frequently aggravated by anorexia (loss of appetite). Their concurrence is often referred to as anorexia–cachexia syndrome. This review focusses on the recent evidence underlining hypothalamic inflammation as key driver of these processes. Special attention is given to the involvement of hypothalamic serotonin. Recent findings The anorexia–cachexia syndrome is directly associated with higher mortality in cancer patients. Recent reports confirm its severe impact on the quality of life of patients and their families. Hypothalamic inflammation has been shown to contribute to muscle and adipose tissue loss in cancer via central hypothalamic interleukine (IL)1&bgr;-induced activation of the hypothalamic–pituitary–adrenal axis. The resulting release of glucocorticoids directly stimulates catabolic processes in these tissues via activation of the ubiquitin–proteosome pathway. Next to this, hypothalamic inflammation has been shown to reduce food intake in cancer by triggering changes in orexigenic and anorexigenic responses via upregulation of serotonin availability and stimulation of its signalling pathways in hypothalamic tissues. This combination of reduced food intake and stimulation of tissue catabolism represents a dual mechanism by which hypothalamic inflammation contributes to the development and maintenance of anorexia and cachexia in cancer. Summary Hypothalamic inflammation is a driving force in the development of the anorexia-cachexia syndrome via hypothalamic–pituitary–adrenal axis and serotonin pathway activation.