role of leptin and tumor necrosis factor- (tnf-) in mechanisms of anorexia during endotoxin infection in mice | ||
| Bulletin of Egyptian Society for Physiological Sciences | ||
| Article 13, Volume 29, Issue 1, June 2009, Pages 149-170 PDF (309.59 K) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/besps.2009.36335 | ||
| Authors | ||
| Mona El Karn* 1; Mohamed Badary2 | ||
| 1Medical Physiology Department, Faculty of Medicine, Assiut University | ||
| 2Microbiology Department, Faculty of Medicine, Assiut University | ||
| Abstract | ||
| Background: Anorexia and loss of body weight are hallmark of infection. The actual mechanisms by which infection induces anorexia are still unknown. Several proinflammatory cytokines, most notably tumor necrotic factor- (TNF-), known to initiate and modulate the host response to infection have been shown to induce anorexia and weight loss in healthy animals. Leptin is a protein hormone produced by adipose tissue. It is considered to be a satiety factor as it decreases food intake and increases energy expenditure. Administration of bacterial endotoxin (LPS) or TNF- induced increase in serum leptin levels, and leptin has been shown to act in an endocrine fashion to decrease food intake and body weight. This suggests that leptin may be one of the mechanisms by which anorexia is induced during infection. The present study aimed to investigate the effect of endotoxin (LPS) and TNF-, on food intake, body weight and serum leptin levels in mice. Also, to explain the different possible mechanisms which can cause anorexia during infection and if leptin is involved in these mechanisms. Methods: The study included 36 adult female mice which were divided into 6 groups, 6 mice each. Group I: “control group”, received single intraperitoneal (i.p) injection of normal saline. Group II, III, IV and V: “LPS treated groups”, received a single i.p. injection of different doses of LPS, (0.1g, 1g, 10g and 100g/100g. body weight respectively). Group VI: “TNF- treated group”, injected i.p. with TNF- in a dose of 17g/100g BW. Food intake and body weight were measured over the next 18, 42, 66 and 90 h for animals of control and LPS treated groups. Food intake by TNF- injected group was measured 18 h after injection. Blood sample from each mouse of all studied animal groups was collected 18 h after different injections, then serum leptin level was assessed using mouse leptin ELISA kits. Results: The study showed a significant (p is<0.001), dose dependent decrease in food intake and body weight 18 h after injection in all LPS injected groups (except for group II which showed a non significant decrease) when compared with that of control group. Gradual recovery of food intake and body weight gaining over the next 3 days occurred in low doses treated groups (groups II & III), while as mice treated with large doses, (group VI & V), showed no food intake nor weight gain over the subsequent 42 h. Thereafter, group IV began to increase their food intake and body weight till the end of the study, whereas group V remained anorectic and losing weight till the end of the study. TNF- injected group showed a significant decrease in food intake, ( p is<0.001) as compared to the control one, that decrease in food intake after TNF- injection is nearly similar to that induced by LPS injection even in high doses injected groups (groups III & IV). Serum leptin levels showed significant increase 18 h after LPS and TNF- injection in all injected groups in a dose related manner, compared to that of the control group. The highest dose of LPS injection to group V “100 g / 100 g BW” showed increased serum leptin levels nearly 4 folds to that level of control group. The increase in serum leptin levels after TNF- injection, did not reach the same levels of increase as after LPS injections specially for the high doses of LPS “groups IV and V”. Conclusion: The present study showed that both of LPS and TNF- can induce anorexia and increased leptin level. The decrease in food intake is inversely proportional to the increase in serum leptin. These data suggest a role for leptin in anorexia during LPS infection. Also, the study revealed some possible mechanisms for anorexia during infection through the cooperation between immune activation mediators (cytokines) and some hormonal changes which can induce different host’s immune and metabolic response during infection. As anorexia plays a critical role in chronic inflammatory diseases, it is possible that development of leptin antagonists may play a useful role in decreasing anorexia and wasting of chronic infections such as AIDS. | ||
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