| Full text | |
| Author(s): |
Flatow, Elizabeth A.
[1]
;
Komegae, Evilin N.
[1]
;
Fonseca, Monique T.
[1]
;
Brito, Camila F.
[1]
;
Musteata, Florin M.
[2]
;
Antunes-Rodrigues, Jose
[3]
;
Steiner, Alexandre A.
[1]
Total Authors: 7
|
| Affiliation: | [1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil
[2] Albany Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Albany, NY - USA
[3] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Physiol, Ribeirao Preto - Brazil
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY; v. 313, n. 5, p. R572-R582, NOV 2017. |
| Web of Science Citations: | 5 |
| Abstract | |
To elucidate the role of leptin in acute systemic inflammation, we investigated how its infusion at low, physiologically relevant doses affects the responses to bacterial lipopolysaccharide (LPS) in rats subjected to 24 h of food deprivation. Leptin was infused subcutaneously (0-20 mu g.kg(-1).h(-1)) or intracere-broventricularly (0-1 mu g.kg(-1).h(-1)). Using hypothermia and hypotension as biomarkers of systemic inflammation, we identified the phase extending from 90 to 240 min post-LPS as the most susceptible to modulation by leptin. In this phase, leptin suppressed the rise in plasma TNF-alpha and accelerated the recoveries from hypothermia and hypotension. Suppression of TNF-alpha was not accompanied by changes in other cytokines or prostaglandins. Leptin suppressed TNF-alpha when infused peripherally but not when infused into the brain. Importantly, the leptin dose that suppressed TNF-alpha corresponded to the lowest dose that limited food consumption; this dose elevated plasma leptin within the physiological range (to 5.9 ng/ml). We then conducted in vitro experiments to investigate whether an action of leptin on macrophages could parallel our in vivo observations. The results revealed that, when sensitized by food deprivation, LPS-stimulated peritoneal macrophages can be inhibited by leptin at concentrations that are lower than those reported to promote cytokine release. It is concluded that physiological levels of leptin do not exert a proinflammatory effect but rather an anti-inflammatory effect involving selective suppression of TNF-alpha via an action outside the brain. The mechanism of this effect might involve a previously unrecognized, suppressive action of leptin on macrophage subpopulations sensitized by food deprivation, but future studies are warranted. (AU) | |
| FAPESP's process: | 16/04921-1 - Arterial tonus in septic shock: a new facet to an old problem. |
| Grantee: | Alexandre Alarcon Steiner |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 13/09799-1 - Energy balance and body fluid homeostasis control: from cells to the physiological systems |
| Grantee: | José Antunes Rodrigues |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 14/03719-9 - Role of leptin in regulation of systemic inflammation |
| Grantee: | Evilin Naname Komegae |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 12/03831-8 - Linking energy balance to systemic inflammation: role of leptin |
| Grantee: | Alexandre Alarcon Steiner |
| Support Opportunities: | Research Grants - Young Investigators Grants |