L-Carnitine Administration and Withdrawal Affect Plasma and Hepatic Carnitine Concentrations, Plasma Lipid and Lipoprotein Composition, and In Vitro Hepatic Lipogenesis from Labeled Mevalonate and Oleate in Normal Rabbits

Ascited hepatoma (AH41C or AH130) was transplanted to male rats Donryu, strain. Plasma cholesterol, triglyceride (TG) and non-esterified fatty acid levels were reduced with oral administration of ginseng principle fraction 3 (saponin content, ca. 1/5). Incorporation of 1-[14C]-acetate into total lipids and fatty acids in adipose tissue was increased by fraction 3 administration in both normal and tumor-bearing rats. The incorporation increased in earlier stage of tumor growth and decreased in the later one. Incorporation of 1-[14C]-acetate into total lipid, free and esterified cholesterol, TG and phospholipid in the liver was also enhanced by fraction 3 administration in both normal and tumor-bearing animals. In vitro addition of ginseng principle fraction 4 (saponin content, ca. 1/2) increased incorporation of 1-[14C]-acetate into lipid fraction is adipose tissue and liver. Incorporation of 1-[14C]-acetate into lipid fractions in ascites hepatoma cells remained unchanged with both oral administration of fraction 3 and in vitro addition of fraction 4. DNA and protein synthesis in the tumor cells was not changed with in vitro addition of fraction 4.

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Utilization of acetate-1-C14 by hepatic tissue from cold-exposed and hibernating hamsters

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1961.200.5.1043 ◽

1961 ◽

Vol 200 (5) ◽

pp. 1043-1046 ◽

Cited By ~ 22

Author(s):

Arliss Denyes ◽

Joan D. Carter

Keyword(s):

Cold Exposure ◽

Hepatic Tissue ◽

Hepatic Lipogenesis ◽

Control Value

When the hamster is exposed to cold (6 ± 1 C), there is a profound block in hepatic lipogenesis from C14-acetate within 48 hr. By 8 weeks of cold exposure this block has been repaired to 74% of the control value. During hibernation, which generally occurs after the 8th week, a block in lipogenesis is again present. By 6 hr of arousal, the degree of lipogenesis has been either slightly repaired or has returned almost to the 8-week level. Accompanying this block in lipogenesis is an increase in the production of C14O2 from C14-acetate in animals exposed to cold. In vitro addition of .02 m glucose did not stimulate lipogenesis in hepatic tissue of cold-exposed hamsters, except for a few of those animals aroused from hibernation for 6 hr. Addition of .02 m succinate in vitro did not increase lipogenesis or C14O2 production from C14-acetate. Fructose repaired the hepatic lipogenesis in all groups of cold-exposed hamsters. It was concluded that the cold-exposed and hibernating hamster has biochemical lesions involving the glucokinase reaction and some other step in the glycolytic pathways of the liver.

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Validity of the Lipid Sink as a Mechanism for the Reversal of Local Anesthetic Systemic Toxicity

Anesthesiology ◽

10.1097/aln.0b013e31828ce74d ◽

2013 ◽

Vol 118 (6) ◽

pp. 1350-1361 ◽

Cited By ~ 41

Author(s):

Ilin Kuo ◽

Belinda S. Akpa

Keyword(s):

Ex Vivo ◽

Aqueous Media ◽

Plasma Lipid ◽

Small Animal ◽

Initial Study ◽

Quantitative Agreement ◽

Systemic Toxicity ◽

Pharmacokinetic Data ◽

Tissue Content

Abstract Background: In vitro observations support the lipid sink theory of therapeutic action by confirming the capacity of lipid emulsions to successfully uptake bupivacaine from aqueous media. However, competing hypotheses and some in/ex vivo small animal studies suggest that a metabolic or positive inotropic effect underlies the dramatic effects of lipid therapy. Controlled clinical tests to establish causality and mechanism of action are an impossibility. In an effort to quantitatively probe the merits of a “sink” mechanism, a physiologically based pharmacokinetic model has been developed that considers the binding action of plasma lipid. Methods: The model includes no fitting parameters and accounts for concentration dependence of plasma protein and lipid:anesthetic binding as well as the metabolism of the lipid scavenger. Predicted pharmacokinetics were validated by comparison with data from healthy volunteers administered a nontoxic dose of bupivacaine. The model was augmented to simulate lipid therapy and extended to the case of accidental IV infusion of bupivacaine at levels known to cause systemic toxicity. Results: The model yielded quantitative agreement with available pharmacokinetic data. Simulated lipid infusion following an IV overdose was predicted to yield (1) an increase in total plasma concentration, (2) a decrease in unbound concentration, and (3) a decrease in tissue content of bupivacaine. Conclusions: Results suggest that the timescale on which tissue content is reduced varies from organ to organ, with the concentration in the heart falling by 11% within 3 min. This initial study suggests that, in isolation, the lipid sink is insufficient to guarantee a reversal of systemic toxicity.

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Human CETP lacks lipopolysaccharide transfer activity, but worsens inflammation and sepsis outcomes in mice

The Journal of Lipid Research ◽

10.1194/jlr.ra120000704 ◽

2020 ◽

pp. jlr.RA120000704

Author(s):

Aloïs Dusuel ◽

Valérie Deckert ◽

Jean-Paul PAIS DE BARROS ◽

Kevin Van Dongen ◽

Hélène Choubley ◽

...

Keyword(s):

Cecal Ligation ◽

Plasma Lipid ◽

Plasma Lipoproteins ◽

Protective Effects ◽

Lipid Transfer ◽

Transfer Property ◽

Transfer Activity ◽

Lps Binding

Bacterial lipopolysaccharides (LPSs or endotoxins) can bind most proteins of the lipid transfer/LPS-binding protein (LT/LBP) family in host organisms. The LPS-bound LT/LBP proteins then trigger either an LPS-induced proinflammatory cascade or LPS binding to lipoproteins that are involved in endotoxin inactivation and detoxification. Cholesteryl ester transfer protein (CETP) is an LT/LBP member, but its impact on LPS metabolism and sepsis outcome is unclear. Here, we performed fluorescent LPS transfer assays to assess the ability of CETP to bind and transfer LPS. The effects of intravenous (iv) infusion of purified LPS or polymicrobial infection (cecal ligation and puncture [CLP]) were compared in transgenic mice expressing human CETP and wild-type mice naturally having no CETP activity. CETP displayed no LPS transfer activity in vitro, but it tended to reduce biliary excretion of LPS in vivo. The CETP expression in mice was associated with significantly lower basal plasma lipid levels and with higher mortality rates in both models of endotoxemia and sepsis. Furthermore, CETPTg plasma modified cytokine production of macrophages in vitro. In conclusion, despite having no direct LPS binding and transfer property, human CETP worsens sepsis outcomes in mice by altering the protective effects of plasma lipoproteins against endotoxemia, inflammation, and infection.

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Comparative Phytochemical, Antioxidant, and Hemostatic Studies of Extract and Four Fractions from Paulownia Clone in Vitro 112 Leaves in Human Plasma

Molecules ◽

10.3390/molecules25194371 ◽

2020 ◽

Vol 25 (19) ◽

pp. 4371

Author(s):

Weronika Adach ◽

Jerzy Żuchowski ◽

Barbara Moniuszko-Szajwaj ◽

Malgorzata Szumacher-Strabel ◽

Anna Stochmal ◽

...

Keyword(s):

Oxidative Stress ◽

Phenolic Compounds ◽

Human Plasma ◽

Antioxidant Properties ◽

Plasma Lipid ◽

Inhibitory Effect ◽

Climate Conditions ◽

Positive Effects ◽

Chemical Content

Background: The Paulownia Clone in Vitro 112, known as oxytree or oxygen tree, is a hybrid clone of the species Paulownia elongata and Paulownia fortunei (Paulowniaceae). The oxytree is a fast-growing hybrid cultivar that can adapt to wide variations in edaphic and climate conditions. In this work, Paulownia Clone in Vitro 112 leaves were separated into an extract and four fractions (A–D) differing in chemical content in order to investigate their chemical content using LC-MS analysis. The extract and fractions were also evaluated for their anticoagulant and antioxidant properties in a human plasma in vitro. Results: The Paulownia leaf extract contained mainly phenolic compounds (e.g., verbascoside), small amounts of iridoids (e.g., aucubin or 7-hydroxytometoside) and triterpenoids (e.g., maslinic acid) were also detected. Our results indicate that the extract and fractions have different effects on oxidative stress in human plasma treated with H2O2/Fe in vitro, which could be attributed to differences in their chemical content. For example, the extract and all the fractions, at the two highest concentrations of 10 and 50 µg/mL, significantly inhibited the plasma lipid peroxidation induced by H2O2/Fe. Fractions C and D, at all tested concentrations (1–50 µg/mL) were also found to protect plasma proteins against H2O2/Fe-induced carbonylation. The positive effects of fraction C and D were dependent on the dose. Conclusions: The extract and all four fractions, but particularly fractions C and D, which are rich in phenolic compounds, are novel sources of antioxidants, with an inhibitory effect on oxidative stress in human plasma in vitro. Additionally, the antioxidant potential of fraction D may be associated with triterpenoids.

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In vitro hepatic lipogenesis in the hen and chick

Comparative Biochemistry and Physiology ◽

10.1016/0010-406x(69)91357-7 ◽

1969 ◽

Vol 28 (1) ◽

pp. 431-435 ◽

Cited By ~ 50

Author(s):

Gilbert A. Leveille

Keyword(s):

Hepatic Lipogenesis

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Physical inactivity amplifies the sensitivity of skeletal muscle to the lipid-induced downregulation of lipoprotein lipase activity

Journal of Applied Physiology ◽

10.1152/japplphysiol.00925.2005 ◽

2006 ◽

Vol 100 (1) ◽

pp. 249-257 ◽

Cited By ~ 94

Author(s):

Theodore W. Zderic ◽

Marc T. Hamilton

Keyword(s):

Skeletal Muscle ◽

Lipoprotein Lipase ◽

Physical Inactivity ◽

Plasma Lipids ◽

Plasma Lipid ◽

The Metabolic Syndrome ◽

Tnf Α ◽

Ordinary Light ◽

Oxide Synthase

Physical inactivity is a risk factor for lipoprotein disorders and the metabolic syndrome. Physical inactivity has a powerful effect on suppressing lipoprotein lipase (LPL) activity in skeletal muscle, the rate-limiting enzyme for hydrolysis of triglyceride (TG)-rich lipoproteins. We tested the ability of several compounds to prevent the decrease in LPL. The present study minimized standing and ordinary light nonexercise movements in rats to compare the effects of inactivity and nonexercise activity thermogenesis (NEAT) on LPL activity. The key new insight was that the typically quick decrease in LPL activity of oxidative muscle caused by physical inactivity was prevented by nicotinic acid (NA), whereas inhibitors of TNF-α, inducible nitric oxide synthase, and NF-κB had no such effect. NA was administered at a dose known to acutely impede the appearance of plasma TG from the liver and free fatty acids from adipose tissue, and it was effective at intentionally lowering plasma lipid concentrations to the same level in active and inactive groups. As measured from heparin-releasable LPL activity, LPL in the microvasculature of the most oxidative muscles was ∼90% lower in the inactive group compared with controls, and this suppression was completely blocked by NA. In contrast to inactivity, NA did not raise muscle LPL in ambulatory controls, whereas a large exogenous fat delivery did decrease LPL activity. In vitro control studies revealed that NA did not have a direct effect on skeletal muscle LPL activity. In conclusion, physical inactivity amplifies the ability of plasma lipids to suppress muscle LPL activity. The light ambulatory contractions responsible for NEAT are sufficient for mitigating these deleterious effects.

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Tributyrin attenuates obesity-associated inflammation and insulin resistance in high-fat-fed mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00053.2012 ◽

2012 ◽

Vol 303 (2) ◽

pp. E272-E282 ◽

Cited By ~ 77

Author(s):

Marco Aurélio Ramirez Vinolo ◽

Hosana G. Rodrigues ◽

William T. Festuccia ◽

Amanda R. Crisma ◽

Vitor S. Alves ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Plasma Lipid ◽

Peritoneal Macrophages ◽

High Fat ◽

Beneficial Effects ◽

Treatment And Prevention ◽

Inflammatory Status

The aim of this study was to investigate whether treatment with tributyrin (Tb; a butyrate prodrug) results in protection against diet-induced obesity and associated insulin resistance. C57BL/6 male mice fed a standard chow or high-fat diet were treated with Tb (2 g/kg body wt, 10 wk) and evaluated for glucose homeostasis, plasma lipid profile, and inflammatory status. Tb protected mice against obesity and obesity-associated insulin resistance and dyslipidemia without food consumption being affected. Tb attenuated the production of TNFα and IL-1β by peritoneal macrophages and their expression in adipose tissue. Furthermore, in the adipose tissue, Tb reduced the expression of MCP-1 and infiltration by leukocytes and restored the production of adiponectin. These effects were associated with a partial reversion of hepatic steatosis, reduction in liver and skeletal muscle content of phosphorylated JNK, and an improvement in muscle insulin-stimulated glucose uptake and Akt signaling. Although part of the beneficial effects of Tb are likely to be secondary to the reduction in body weight, we also found direct protective actions of butyrate reducing TNFα production after LPS injection and in vitro by LPS- or palmitic acid-stimulated macrophages and attenuating lipolysis in vitro and in vivo. The results, reported herein, suggest that Tb may be useful for the treatment and prevention of obesity-related metabolic disorders.

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