Peptidoglycan fragments decrease food intake and body weight gain in rats

Abstract

We hypothesized that peptidoglycan (PG) fragments decrease appetite in rats. Male Lewis rats (150 g; n 2 7) received intraperitoneal (i.p.) injections of purified soluble PG fragments that had been treated with polymyxin B-agarose to remove residual endotoxin. Food consumption and body weight gain were determined at intervals after injection. Single i.p. injections of macromolecular extensively O-acetylated PG (S-O-PG) and non-O-acetylated PG fragments (24 to 240 ,ug/kg) reduced food intake and body weight gain in a dosedependent fashion during the first 12 h after injection. Low-molecular-weight disaccharide peptide monomers with nonreducing 1,6-anhydro-N-acetylmuramic acid ends and muramyl dipeptide (MDP; 1.6 mg/kg) were also appetite and weight gain suppressants, albeit at least 10-fold less potent than SO -PG; however, muramidasederived monomers and peptide cross-linked dimers with reducing muramic acid ends were inactive. Appetite suppression was not limited to the Lewis rat strain since another strain, F344, exhibited similar decreases in food intake after injection of SO -PG or MDP. Oral administration of MDP or SO -PG, at concentrations 3 and 20 times higher, respectively, than those that were active i.p., failed to elicit a hypophagic response. We conclude that soluble PG fragments are potent suppressants of food consumption and body weight gain in rats and that, although macromolecular PG is more potent than low-molecular-weight fragments, neither O-acetylation nor glycosidic linkage of PG fragments is required for activity. We speculate that PG fragments may contribute to loss of appetite during bacterial illness.

Synergistic effects of NOD1 or NOD2 and TLR4 activation on mouse sickness behavior in relation to immune and brain activity markers

“…However, this argument is relativized by the finding that a higher dose of MDP (3 mg/kg) given to double-housed mice outside the LabMaster system failed to cause weight loss within 1 day after treatment. This observation is in keeping with studies in rats in which MDP failed to reduce body weight ( Cloutier et al, 2012; Engeland et al, 2003 ) although weight gain may be decreased ( Biberstine and Rosenthal, 1994 ). FK565 (0.001 mg/kg) reduced food intake by trend when given to single-housed mice, whereas no appreciable weight loss was observed 21 h after injection of a higher dose of FK565 (0.003 mg/kg) in double-housed animals.…”

“…Food intake in the LabMaster system remained likewise unaltered by MDP. MDP has been reported to reduce food intake at 1.6 mg/kg in rats, while a dose of 0.6 mg/kg was ineffective ( Biberstine and Rosenthal, 1994; Fosset et al, 2003; Langhans et al, 1990 ). Thus, the dose of 1 mg/kg MDP used here might have been too low to affect ingestion.…”

Tolerance to appetite suppression induced by peptidoglycan

“…Rat appetite model. Food consumption and body weight gain of rats were determined as described previously (3). Overnight food consumption was measured during the 12-h period beginning at the time of injection, approximately 1900 h. Rats were divided into experimental and control groups of typically nine or more per group and injected i.p.…”

“…All of the reagents were suspended in saline. S-O-PG was treated with polymyxin B-agarose to reduce endotoxin contamination as described previously (3). We determined previously (3) that contaminating LPS did not account for the hypophagic qualities of PG preparations.…”

Detection of peptidoglycan in human plasma using the silkworm larvae plasma test

“…PG is a component accounting for about 70% and 20% of the Gram‐positive and Gram‐negative bacterial cell wall, respectively. It has been demonstrated that various biological activities were induced by PG [4–6], including the induction of a variety of cytokines [7,8] and shock under experimental conditions [9,10]. It has been demonstrated that endotoxin and PG share a common binding site on human peripheral mononuclear cells [11], suggesting that the components of Gram‐positive bacteria play an important role in the pathogenesis of mixed infection with Gram‐positive and Gram‐negative bacteria by enhancing many biological activities of endotoxin [12,13].…”