Abstract
Bacterial endotoxin lipopolysaccharide (LPS)-induced sepsis is a critical medical condition, characterized by a severe systemic inflammation and rapid loss of muscle mass. Preventive and therapeutic strategies for this complex disease are still lacking. Here, we evaluated the effect of omega-3 (n-3) polyunsaturated fatty acid (PUFA) intervention on LPS-challenged mice with respect to inflammation, body weight and the expression of Toll-like receptor 4 (TLR4) pathway components. LPS administration induced a dramatic loss of body weight within two days. Treatment with n-3 PUFA not only stopped loss of body weight but also gradually reversed it back to baseline levels within one week. Accordingly, the animals treated with n-3 PUFA exhibited markedly lower levels of inflammatory cytokines or markers in plasma and tissues, as well as down-regulation of TLR4 pathway components compared to animals without n-3 PUFA treatment or those treated with omega-6 PUFA. Our data demonstrate that n-3 PUFA intervention can suppress LPS-induced inflammation and weight loss via, at least in part, down-regulation of pro-inflammatory targets of the TLR4 signaling pathway, and highlight the therapeutic potential of n-3 PUFA in the management of sepsis.
Highlights
Sepsis is a potentially life-threatening complication of an infection, characterized by a systemic inflammatory response syndrome and rapid loss of muscle mass and myofibrillar protein content, or muscle atrophy [1,2]
Supplementation of the LPS-challenged mice with fish oil containing 63% EPA and DHA stopped BW drop and even raised it gradually, resulting in a significant difference in BW on Day 8 between the animals treated with FO (LPS + FO) and those without supplementation (LPS) or with corn oil
Consistent with these observations, we found that FO intervention resulted in decreased tissue levels of tumor necrosis factor-α (TNF-α), IL-1β, and IL-6 and decreased plasma alanine transaminase (ALT) and aspartate transaminase (AST)
Summary
Sepsis is a potentially life-threatening complication of an infection, characterized by a systemic inflammatory response syndrome and rapid loss of muscle mass and myofibrillar protein content, or muscle atrophy [1,2]. Nutritional modulation aimed at suppressing the release of pro-inflammatory cytokines and preventing weight loss may be of potential benefit in attenuating muscle atrophy and inflammation during sepsis. Omega-3 PUFA have been shown to improve muscle protein synthesis [7,8], and alleviate muscle atrophy in cancer [9] and sepsis [10]. These data suggest that n-3 PUFA represent potentially novel therapeutic agents for critically ill and severely injured patients who commonly present with inflammation and weight loss problems. Whether FO intervention is effective in suppressing LPS-induced inflammation and weight loss requires further investigation. The beneficial role of n-3 PUFA is thought to be associated with their inhibitory effects on overproduction of pro-inflammatory cytokines [4,5,6], the specific signaling pathways are unclear
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