GAPS FACTS
 
 
 Home

 Science

 Probiotic

 Intro Diet

 Success Rate

 Facts vs Hype

 Dr. NCM

 Detoxification

 SCD is already proven while GAPS is still in the experimental stage. Click here for proof


Fat Malabsorption and LPS

LPS disrupts fat absorption and can cause fat malabsorption because it decreases bile flow and bile acid secretion.
( Bile is secreted by the liver to aid in the digestion of fats). LPS also decreases lipoprotein lipase levels in different parts of the body which creates fat malabsorption because the enzyme lipoprotein lipase plays a central role in lipid metabolism.

This article shows that LPS decreased the bile flow and the bile acid secretion of cats.

View this article
1: Korean J Hepatobiliary Pancreat Surg. 2000 Oct;4(2):27-33. Korean.

The Effect of Escherichia coli Lipopolysaccharide on the Flow of Bile in the Cat.

Choi JW, Jung YS, Park JW, Jin H, Lim SW.

Department of Surgery, College of Medicine, Chungbuk National University. Department of Anesthesiology, College of Medicine, Chungbuk National University. Postgraduate Department Yanbian University.

Pathophysiological conditions such as sepsis and hepatitis are frequently associated with cholestasis. Cholestasis in patients with sepsis has been attributed to the effects of endotoxin(lipopholysaccharides, LPS) and LPS-induced cytokines(TNF-a, IL-6, IL-1, etc.). LPS and cytokines reduced bile acid uptake in cultured hepatocyte. Perfusion of LPS decrease the bile flow in the isolated liver. Bile flow is increased by intravenous infusion of secretin, but it's effect remains unclear in sepsis. The aim, of this study is to elucidate the effect of LPS on the bile flow and bile composition and to test the effect of secretin on the bile flow. The animals used in this study were Korean wild cats. Under the general anesthesia, the incision was made on the midline. Common bile duct was cannulated with polyethylene tube after cholecystectomy. Bile was collected every five minutes and its volume was measured. E. coli LPS(1 mg/kg), secretin(0.1mg/kg) and H3-taurocholic acid(0.2uCi/kg) were infused via mesenteric vein. Bile was collected every 5 minutes, and the volume and its composition were analyzed. Radio-activity of the bile was quantified by Packard 1600 TR liquid scintillation analyzer. LPS of E.coli (1mg/kg) had a little effect on the blood pressure. LPS decreased the bile flow by 37% compared with the control group. Maximal impairment of the bile secretion appeared 15 minites after LPS infusion, and then secreted stablely thereafter. Secretin increased the bile flow in the normal control group. It, however, did not make any change in the bile flow after LPS infusion. LPS also reduced H3-taurocholate secretion(maximum 56%), and peak level was delayed about 10 minites compared with control group. In the composition of the bile, LPS decreased the secretion of bile acids significantly compared with the control group. Conclusively, LPS decreased the bile flow and the bile acid secretion. Secretin did not stimulate the bile flow in the LPS group. It also reduced the bile acids secretion compared with the control group. These findings will contribute to the understanding and treatment of the cholestasis and impairment of the liver function of sepsis. The findings, of reduced bile acids secretion in the LPS group may explain the pathogenesis of intrahepatic gallstone partly.


The enzyme lipoprotein lipase (LPL) plays a central role in lipid metabolism. The next articles show how LPS decreases lipoprotein lipase levels in different parts of the body thus creating fat malabsorption.


View this article in PubMed
Infect Immun. 1995 March; 63(3): 858?864.

Lipopolysaccharide regulation of lipoprotein lipase expression in murine macrophages.

M R Hill, K Kelly, X Wu, F Wanker, H Bass, C Morgan, C Wang, and J M Gimble Department of Radiation Technology, University of Oklahoma Health Sciences Center, Oklahoma City 73104.

The enzyme lipoprotein lipase is expressed in a number of cell types and plays a central role in lipid metabolism. Multiple factors regulate its expression in a tissue-specific manner. In murine macrophages, lipopolysaccharide inhibits lipoprotein lipase enzyme activity. The current work examines this process in the established J774 macrophage line and primary peritoneal macrophages from endotoxin-sensitive (C3HeB/Fej) and endotoxin-resistant (C3H/Hej) murine strains. Lipopolysaccharide inhibition of macrophage lipoprotein lipase occurred at the enzyme and mRNA levels in a time- and concentration-dependent manner. Cells from endotoxin-resistant animals maintained their expression of lipoprotein lipase following treatment with lipopolysaccharide. Results of gel retention assays showed that lipopolysaccharide treatment of the J774 macrophages altered the level of nuclear proteins recognizing and binding the lipoprotein lipase promoter DNA. Nuclear extracts from resting J774 cells contained proteins which bound specifically to the octamer motif and to the CAAT box within the lipoprotein lipase promoter. Exposure of the J774 cells to lipopolysaccharide for 16 h increased the level of protein-octamer DNA complexes. Similar responses were obtained in endotoxin-sensitive, but not endotoxin-resistant, primary macrophages following in vitro treatment with lipopolysaccharide. This finding suggests that transcriptional events may contribute to the lipopolysaccharide regulation of macrophage lipoprotein lipase expression.


View this article in PubMed
1: J Lipid Res. 1988 Oct;29(10):1379-85.

Bacterial lipopolysaccharide reduces macrophage lipoprotein lipase levels: an effect that is independent of tumor necrosis factor.

White JR, Chait A, Klebanoff SJ, Deeb S, Brunzell JD.

Department of Medicine, University of Washington, Seattle 98195.

Human monocyte-derived macrophages secrete lipoprotein lipase (LPL) in culture. The regulation of human macrophage LPL production is poorly understood. Since bacterial lipopolysaccharide (LPS) alters production of several macrophage secretory products, its effect on human monocyte-derived macrophage LPL was tested. LPS treatment produced a dramatic dose-dependent decrease in LPL activity in macrophage-conditioned media. At 100 ng/ml LPS, medium LPL activity dropped by 60%. The effect of LPS on macrophage LPL activity was rapid, was blocked by polymixin B, and was not due to cytotoxicity. LPS lowers (by about 60%) the steady state level of LPL mRNA, suggesting that its effect is exerted at the level of mRNA metabolism. Since LPS stimulates macrophage production of cachectin/tumor necrosis factor (TNF), a potent inhibitor of LPL production by the 3T3-L1 adipocyte-like cell line, it was determined whether TNF reduces macrophage LPL levels. Treatment of human macrophages with up to 1000 U/ml of recombinant human TNF had no effect on macrophage LPL activity. When TNF was added in combination with LPS, no additional effect on LPL activity was observed over that seen with LPS alone. Furthermore, the LPS effect was not blocked by a monoclonal anti-TNF antibody. Thus, bacterial LPS potently decreases macrophage LPL activity and mass independent of an autocrine effect of TNF.

. PMID: 3235920 [PubMed - indexed for MEDLINE]


View this article in PubMed
1: Biosci Biotechnol Biochem. 1996 Mar;60(3):528-9.

Responses of serum lipids and adipose tissue lipases to lipopolysaccharide administration in normal and hepatoma-bearing rats.

Kawasaki M, Yagasaki K, Miura Y, Funabiki R.

Department of Applied Biological Science, Tokyo Noko University, Japan.

The effects of in vivo lipopolysaccharide administration on serum lipid metabolism were studied in normal and hepatoma-bearing rats. Changes in serum lipid levels and adipose tissue lipase (lipoprotein lipase and hormone-sensitive lipase) activities following injection of lipopolysaccharide into normal rats resembled those in hepatoma-bearing rats. These results suggest the presence of some common factor(s) involved in the incidence of abnormal lipid metabolism upon lipopolysaccharide injection and hepatoma transplantation.

PMID: 8901118 [PubMed - indexed for MEDLINE]