Alterations of Plasma Ghrelin Levels in Rats with Lipopolysaccharide-Induced Wasting Syndrome and Effects of Ghrelin Treatment on the Syndrome

Abstract

Ghrelin not only strongly stimulates GH secretion, but is also involved in energy homeostasis by stimulating food intake and promoting adiposity through a GH-independent mechanism. These effects of ghrelin may play an important role in the pathophysiology of inflammatory wasting syndrome, in which both the somatotropic axis and energy balance are altered. In this study we investigated plasma ghrelin concentrations after lipopolysaccharide (LPS) administration to rats, a model of the wasting syndrome and critical illness. In addition, the therapeutic potential of the antiwasting effects of ghrelin was explored using LPS-injected rats. A single LPS injection suppressed plasma ghrelin levels 6 and 12 h later. Maximal reduction was observed 12 h after LPS injection, in a dose-dependent manner. In contrast, plasma ghrelin levels were elevated after repeated LPS injections on d 2 and 5. Peripheral administration of ghrelin twice daily (10 nmol/rat) for 5 d increased body weight gain in repeated LPS-injected rats. Furthermore, both adipose tissue weight and plasma leptin concentrations were increased after ghrelin administration in these rats. In conclusion, plasma ghrelin levels are altered in LPS-injected rats, and ghrelin treatment may provide a new therapeutic approach to the wasting syndrome and critical illness.

Prostacyclin signaling regulates circulating ghrelin during acute inflammation

“…Thus, an acute decrease in circulating ghrelin would be expected to produce hypophagia by increasing the net melanocortinergic tone in the hypothalamus. Our data, as well as that of others, indicate that circulating ghrelin levels are acutely decreased in the setting of LPS-or cytokine-induced inflammation (Basa et al 2003, Hataya et al 2003, Wang et al 2006. Thus, previous observations that acute anorexia brought about by the administration of LPS or IL-1b is attenuated in models of impaired melanocortin signaling may provide further evidence that the melanocortin system lies downstream of the ghrelin signal to feeding centers in the brain (Lawrence & Rothwell 2001, Marks et al 2001, Joppa et al 2005.…”

“…In contrast to the upregulation of ghrelin with acute and prolonged fasting, decreases in food intake brought about by acute lipopolysaccharide (LPS)-induced inflammation do not result in increased circulating ghrelin in rodents (Basa et al 2003, Hataya et al 2003. LPS is a purified product found in the cell wall of gram-negative bacteria that reliably produces anorexia in experimental animals (Murray & Murray 1979, Baile et al 1981 due to its ability to produce acute inflammation and potently stimulate the release of numerous cytokines.…”

Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells

“…We demonstrate that ghrelin infusions in LPS-challenged mice lead to a significant inhibition of proinflammatory cytokines IL-1α and IL-β, IL-6, and TNF-α in circulation as well as in liver, spleen, lungs, and mesenteric lymph nodes. In addition, LPS-induced endotoxemia results in inhibition of ghrelin secretion (47), and ghrelin infusion increases body weight in septic animals (48). Considering the data presented herein, it seems plausible that inhibition of ghrelin secretion after LPS challenge might exacerbate the ongoing inflammatory insult and promote development of a catabolic state.…”

Translational Research on the Clinical Applications of Ghrelin

“…In an animal model of excessive inflammation, septic shock, and wasting syndrome, repeated ghrelin treatment (twice daily for five days) increased food intake and body weight [36]. Although no clinical trial has been attempted in patients with sepsis, these findings suggest the therapeutic potential of the anti-wasting effects of ghrelin.…”