Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clearance rate of endogenous and exogenous circulating lipids during the septic or inflammatory state remains a controversial subject. Thus, we have developed rat models of gram-negative and gram-positive sepsis and of sterile inflammation to study this problem. In addition to the febrile response, these stresses induced some of the following metabolic changes in the blood: decreased total protein, albumin, and ketone body levels and increased lactate, pyruvate, alanine, cholesterol, and triacylglycerol levels. The activities of heart, diaphragm, and adipose tissue lipoprotein lipase and of hepatic lipase decreased to differing extents depending on whether the enzyme substrate was a long-chain or a medium- and long-chain triglyceride-based emulsion. However, the latter emulsion was always hydrolyzed faster than the former. This observation suggests that, during infection/inflammation, the medium- and long-chain triglyceride-based emulsion would be cleared more quickly, would induce less hypertriglyceridemia, and would thus deliver lipid energy more rapidly than a traditional long-chain triglyceride-based emulsion.
 ...
PMID:Decreased lipolytic activity in tissues during infectious and inflammatory stress. 180 2

To study the influence of a gram-positive sepsis on the metabolism of circulating lipids, fasted rats were injected with saline (control group) or with a suspension of heat-killed or live Staphylococcus aureus. 18 h later, body temperature was increased, while albuminemia and ketonemia were decreased in the group injected with heat-killed bacteria, as opposed to the control group. Passing from these groups to the group injected with live bacteria, more differences appeared: increase of triglyceridemia and free cholesterolemia; decrease of esterified cholesterol levels and especially of the in vitro activity of diaphragm, heart and adipose tissue lipoprotein lipase and of hepatic lipase. The decrease of lipolytic activities occurred whether they were measured on a fat emulsion containing long-chain or medium- and long-chain triglycerides. The fact that for the latter the activity was always higher than for the former suggests that the host infected with gram-positive bacteria would clear exogenous fat more easily in the case of medium-chain triglycerides.
 ...
PMID:Gram-positive bacterial sepsis in rat and tissue lipolytic activity on commercial parenteral fat emulsions. 211 Jan 16

The aim of this study was to evaluate the effect of a gram-negative bacteria sepsis on the activity of the enzymes lipoprotein lipase (LPL) and hepatic lipase (HL), involved in the clearance of circulating triacylglycerol-rich fat particles. Fasting rats were intravenously injected with NaCl9 g.l-1, live or heat-killed Pseudomonas aeruginosa bacteria. After 18 h the animals were killed. When compared to controls, the 2 treated groups showed an increase in body temperature, cholesterolemia, triglyceridemia and a decrease in ketonemia, proteinemia, albuminemia and in the in vitro activity of diaphragm, heart and adipose tissue LPL and of HL. The decrease in the enzyme activities occurred independent of the type of emulsion used as in vitro substrate, whether it was based on long-chain triglycerides or on medium- and long-chain triglycerides, but in any case the activity was lower with the first than with the second type of fat emulsion.
 ...
PMID:Gram-negative bacteria sepsis in the rat and tissue lipolytic activity on LCT and MCT/LCT-based commercial parenteral emulsions. 211 37

The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of [2-3H]glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from fasted control, fasted E. coli-treated, fed control, and fed E. coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli-treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats. 218 49

The effects of sepsis on lipid metabolism may be summarized as follows: The increased plasma catecholamine concentration stimulates adipose tissue FFA release. The increased FFA mobilization and plasma concentration results in an enhanced FFA uptake by the liver which promotes TGFA synthesis and output. Thus, triglyceride appearance rate also can be increased during hypermetabolic sepsis. In severe sepsis, the regulatory signals to increase FFA release from adipose tissue may be counterbalanced by blood flow limitations that inhibit FFA release, possibly due to the inadequate availability of the plasma carrier, albumin. Under such conditions, the arterial FFA concentration may be unchanged or decreased along with similar changes in the rate of peripheral FFA utilization. Triglyceride metabolism can also be altered during septic conditions in which plasma levels of cytokines are very high. Cytokines, notably TNF and IL-1, suppress synthesis of lipoprotein lipase which decreases the rate of TGFA clearance. Thus, hypertriglyceridemia can develop in the absence of elevated plasma FFA levels. The plasma concentration of cytokines necessary to inhibit LPL and how often this form of hypertriglyceridemia occurs in human sepsis are unknown at present. The sequence of events describing the influence of sepsis on carbohydrate metabolism is postulated to be the following: The presence of bacteria, or their products (eg, endotoxin) either directly or indirectly (via stimulating mononuclear phagocytes to release cytokines) activate the immune tissues. Glucose utilization by these tissues, which are predominantly glycolytic, is thereby stimulated resulting in increased lactate production. At the same time, glucose uptake by skeletal muscle and lactate release are also elevated.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Alterations in lipid and carbohydrate metabolism in sepsis. 306 39

Hypertriglyceridemia observed in animals after bacterial endotoxin administration and some forms of sepsis can result from increased hepatic triacylglycerol (TG) output or decreased TG clearance by extrahepatic tissues. To differentiate between these two possibilities, TG and free fatty acid (FFA) kinetics were determined in control and endotoxin-injected (0.1-0.5 mg/100 g) rats 18 h after treatment. Plasma TG and FFA kinetics were assessed by a constant intravenous infusion with [9,10-3H]palmitate-labeled very low-density lipoprotein and [1-14C]palmitate bound to albumin, respectively. In addition, lipoprotein lipase (LPL) activity was determined in heart, skeletal muscle, and adipose tissue as well as in postheparin plasma of functionally hepatectomized, adrenalectomized, and gonadectomized rats. Plasma FFA acid concentrations were slightly increased in endotoxin-treated rats but their turnover did not differ from control. Endotoxin-treated rats had a threefold increase in plasma TG concentrations and decreased heart, skeletal muscle, and post-heparin plasma LPL activity. Plasma TG turnover was decreased, indicating that hypertriglyceridemia was not due to an increased TG output by the liver. Instead, the endotoxin-induced increase in plasma TG concentration was a consequence of the 80% reduction in TG metabolic clearance rate. Thus, suppression of LPL activity in endotoxic animals impairs TG clearance resulting in hypertriglyceridemia. Furthermore, endotoxin administration reduced the delivery of TG-FFA to extrahepatic tissues because hepatic synthesis and secretion of TG from plasma FFA was decreased and LPL activity was suppressed.
 ...
PMID:Triacylglycerol kinetics in endotoxic rats with suppressed lipoprotein lipase activity. 360 34

The rats were used for the study of the effects of sepsis on the utilization of exogenous fat emulsion. The studies were carried out by measuring the rate and the pattern of clearance of intravenously-administered 14C-Intralipid from the plasma, liver, spleen, kidney, and muscle of control and septic rats. Plasma clearance of the exogenous fat measured for 14C at 30, 60, 90, 120, 360 min (n = 5) after intravenous injection revealed that the clearance was retarded by sepsis. In the liver, the initial 14C uptake was much greater in the septic rats than those in the control group (34.8 +/- 3.6% vs 14.4 +/- 1.6%, p less than 0.01). Six hr after injection, as high as 19.6 +/- 2.4% of the injected dose was detected in the liver of the septic rats, but the control rats had only 4.4 +/- 0.8%. In spleen, kidney, and muscle, however, both the 14C uptake and the rate of its clearance were greater for the control rats than those of the septic group. The increase in the amount of liver uptake of the exogenous fat by the septic rat and the retained large amount of the fat may account for the decreased plasma clearance and the decrease in its subsequent utilization by other organs and tissues. Significant increase in liver contents of total lipid and triglyceride with a decrease in nonesterified fatty acid (NEFA) at the end of a 6-hr period in septic rats suggest that accumulation of fat in the liver may be a result of impaired triglyceride hydrolysis, possibly due to suppressed lipoprotein lipase activity.
 ...
PMID:Utilization of Intralipid in septic rats: effects of sepsis on the clearance of exogenous fat emulsion from various organs. 376 23

The role of the macrophage system in shock pathogenesis now embraces both classic endocytic functions as well as the more recently discovered function of the macrophages as a multifaceted secretory apparatus. Among the major macrophage secretory products are the monokines, regulatory proteins that mediate via both local or paracrine and systemic or endocrine mechanisms, the nonspecific host defense and metabolic responses to inflammation and sepsis. Evidence is reviewed for a monokine involvement in the alterations of protein, fat, and carbohydrate metabolism in sepsis and/or endotoxicosis, viz., enhanced muscle proteolysis, enhanced hepatic acute phase protein synthesis, depressed lipogenesis and lipoprotein lipase function, enhanced peripheral glucose oxidation, and depression of hepatic gluconeogenesis. Monokines are also related to the disturbed endocrine mechanisms of sepsis, viz., enhanced insulin secretion and depressed adrenal steroidogenesis. It is suggested that the macrophage system mediates via secretion of monokines an integrated fuel substrate and hormonal adjustment to sepsis, which on the one hand may provide optimal metabolic homeostasis for systemic host defense, but on the other hand, if allowed to act unchecked, may contribute to the metabolic dyshomeostasis of septic shock.
 ...
PMID:Monokines and the metabolic pathophysiology of septic shock. 388 Dec 89

Hypertriglyceridemia, commonly observed in septic patients, may result from a decreased ability of tissues to remove plasma triacylglycerol due to depressed lipoprotein lipase activity. While endotoxin administration results in substantial decreases in muscle lipoprotein lipase activity, enzyme activity is increased in animals subjected to other forms of stress and trauma. The present study was initiated to compare changes in plasma triacylglycerol concentrations and tissue lipoprotein lipase activities in rats challenged with endotoxin or live Escherichia coli (iv or ip) or rats subjected to polymicrobial peritoneal sepsis. Sixteen hours post-treatment plasma triacylglycerol levels were increased 200 to 300% in endotoxin- and E. coli-treated rats but did not differ from control animals subjected to peritoneal sepsis. At the same time, endotoxin administration resulted in significant decreases in heart (71-80%), soleus muscle (52-74%), and adipose tissue (21-32%) lipoprotein lipase activity regardless of the route injected. Intravenous E. coli also lead to a decrease in the three tissues examined while ip administration of E. coli reduced muscle and adipose tissue but not heart lipoprotein lipase activity. In contrast to endotoxemic and E. coli bacteremic rats, polymicrobial peritonitis resulted in significant increases in heart (46-89%) and skeletal muscle (18-39%) lipoprotein lipase activity. Thus, hypertriglyceridemia is not necessarily a consequence of sepsis but occurred in endotoxemic and bacteremic states when muscle and adipose tissue lipoprotein lipase activities were reduced. These findings support the postulate that sepsis-induced hypertriglyceridemia is likely to be associated with a decreased ability of lipoprotein lipase-containing tissues to clear circulating triacylglycerol.
 ...
PMID:Hypertriglyceridemia and its relation to tissue lipoprotein lipase activity in endotoxemic, Escherichia coli bacteremic, and polymicrobial septic rats. 638 77

Hypertriglyceridemia commonly accompanies clinical sepsis and may be caused by increased hepatic production or decreased clearance of triglyceride from the bloodstream. In contrast, enhanced lipid clearing capacity is usually seen after uncomplicated trauma. The purpose of the study was to determine the role of lipoprotein lipase (LPL) in effecting the above changes. Enzyme activity was assayed in skeletal muscle and adipose tissue biopsy samples from 11 normal subjects and from 17 injured and 11 infected surgical patients. Normal subjects after 4 days of 5% dextrose infusion (D5) showed a significant decrease in adipose tissue LPL activity but no change in skeletal muscle activity. Trauma patients after several days of D5 had higher activity in adipose tissue and higher plasma insulin levels than diet-matched control subjects but showed no change in skeletal muscle activity. Infected patients with high plasma triglyceride levels had significantly decreased LPL activity in both tissues. A linear relationship was found between insulin concentration and adipose tissue LPL activity in normal subjects. We conclude that: (1) low tissue LPL activity in sepsis may result in diminished lipid clearance and contribute to hypertriglyceridemia, (2) after trauma, changes in tissue LPL activity as well as other factors such as altered hemodynamics play a role in determining in vivo lipid clearance, and (3) adipose tissue LPL activity is related to the plasma insulin concentration in normal subjects.
 ...
PMID:Lipoprotein lipase activity in surgical patients: influence of trauma and infection. 702 Jan 40


1 2 3 Next >>