Role of Nonesterified Fatty Acids in Necrotizing Pancreatitis: An In Vivo Experimental Study in Rats

We have previously shown that secreted phospholipases A2(sPLA2s) from animal venoms inhibit thein vitrodevelopment ofPlasmodium falciparum, the agent of malaria. In addition, the inflammatory-type human group IIA (hGIIA) sPLA2circulates at high levels in the serum of malaria patients. However, the role of the different human sPLA2s in host defense againstP. falciparumhas not been investigated. We show here that 4 out of 10 human sPLA2s, namely, hGX, hGIIF, hGIII, and hGV, exhibit potentin vitroanti-Plasmodiumproperties with half-maximal inhibitory concentrations (IC50s) of 2.9 ± 2.4, 10.7 ± 2.1, 16.5 ± 9.7, and 94.2 ± 41.9 nM, respectively. Other human sPLA2s, including hGIIA, are inactive. The inhibition is dependent on sPLA2catalytic activity and primarily due to hydrolysis of plasma lipoproteins from the parasite culture. Accordingly, purified lipoproteins that have been prehydrolyzed by hGX, hGIIF, hGIII, and hGV are more toxic toP. falciparumthan native lipoproteins. However, the total enzymatic activities of human sPLA2s on purified lipoproteins or plasma did not reflect their inhibitory activities onP. falciparum. For instance, hGIIF is 9-fold more toxic than hGV but releases a lower quantity of nonesterified fatty acids (NEFAs). Lipidomic analyses of released NEFAs from lipoproteins demonstrate that sPLA2s with anti-Plasmodiumproperties are those that release polyunsaturated fatty acids (PUFAs), with hGIIF being the most selective enzyme. NEFAs purified from lipoproteins hydrolyzed by hGIIF were more potent at inhibitingP. falciparumthan those from hGV, and PUFA-enriched liposomes hydrolyzed by sPLA2s were highly toxic, demonstrating the critical role of PUFAs. The selectivity of sPLA2s toward low- and high-density (LDL and HDL, respectively) lipoproteins and their ability to directly attack parasitized erythrocytes further explain their anti-Plasmodiumactivity. Together, our findings indicate that 4 human sPLA2s are active againstP. falciparumin vitroand pave the way to future investigations on theirin vivocontribution in malaria pathophysiology.

Download Full-text

Role of alpha-1 acid glycoprotein, albumin, and nonesterified fatty acids in serum binding of apazone and warfarin

Clinical Pharmacology & Therapeutics ◽

10.1038/clpt.1986.119 ◽

1986 ◽

Vol 39 (6) ◽

pp. 683-689 ◽

Cited By ~ 21

Author(s):

Saïk Urien ◽

Edith Albengres ◽

Jean-Louis Pinquier ◽

Jean-Paul Tillement

Keyword(s):

Fatty Acids ◽

Nonesterified Fatty Acids ◽

Acid Glycoprotein

Download Full-text

An experimental study of the role of vulnerability related perceptions in spider fear: Comparing an imaginal and in vivo encounter

Journal of Anxiety Disorders ◽

10.1016/j.janxdis.2007.03.003 ◽

2008 ◽

Vol 22 (2) ◽

pp. 222-232 ◽

Cited By ~ 4

Author(s):

Jason M. Armfield

Keyword(s):

Experimental Study ◽

Spider Fear

Download Full-text

Evidence that amylin stimulates lipolysis in vivo: a possible mediator of induced insulin resistance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2001.280.4.e562 ◽

2001 ◽

Vol 280 (4) ◽

pp. E562-E569 ◽

Cited By ~ 13

Author(s):

Ji-Ming Ye ◽

Megan Lim-Fraser ◽

Gregory J. Cooney ◽

Garth J. S. Cooper ◽

Miguel A. Iglesias ◽

...

Keyword(s):

Insulin Resistance ◽

Repeated Measures ◽

Plasma Nefa ◽

Nonesterified Fatty Acids ◽

Similar Tendency ◽

Basal Plasma ◽

Triglyceride Content ◽

Infusion Period

The present study investigated the role of amylin in lipid metabolism and its possible implications for insulin resistance. In 5- to 7-h-fasted conscious rats, infusion of rat amylin (5 nmol/h for 4 h) elevated plasma glucose, lactate, and insulin ( P <0.05 vs. control, repeated-measures ANOVA) with peak values occurring within 60 min. Despite the insulin rise, plasma nonesterified fatty acids (NEFA) and glycerol were also elevated ( P < 0.001 vs. control), and these elevations (80% above basal) were sustained over the 4-h infusion period. Although unaltered in plasma, triglyceride content in liver was increased by 28% ( P < 0.001) with a similar tendency in muscle (18%, P = 0.1). Infusion of the rat amylin antagonist amylin-(8–37) (125 nmol/h) induced opposite basal plasma changes to amylin, i.e., lowered plasma NEFA, glycerol, glucose, and insulin levels (all P < 0.05 vs. control); additionally, amylin-(8–37) blocked amylin-induced elevations of these parameters ( P < 0.01). Treatment with acipimox (10 mg/kg), an anti-lipolytic agent, before or after amylin infusion blocked amylin's effects on plasma NEFA, glycerol, and insulin but not on glucose and lactate. We conclude that amylin could exert a lipolytic-like action in vivo that is blocked by and is opposite to effects of its antagonist amylin-(8–37). Further studies are warranted to examine the physiological implications of lipid mobilization for amylin-induced insulin resistance.

Download Full-text

Obesity increases free thyroxine proportionally to nonesterified fatty acid concentrations in adult neutered female cats

Journal of Endocrinology ◽

10.1677/joe-07-0064 ◽

2007 ◽

Vol 194 (2) ◽

pp. 267-273 ◽

Cited By ~ 28

Author(s):

D C Ferguson ◽

Z Caffall ◽

M Hoenig

Keyword(s):

Fatty Acids ◽

Nonesterified Fatty Acid ◽

Nonesterified Fatty Acids ◽

Before And After ◽

Pituitary Thyroid Axis ◽

Total Thyroxine ◽

Obesity Indices ◽

The Impact

The obese cat is a model for the study of the progression toward type 2 diabetes. In this study, the impact of obesity on the hypothalamic–pituitary–thyroid axis was examined in 21 domestic shorthair cats before and after the development of obesity, which significantly increased body mass index (BMI), % body fat (BF), and girth (P<0.0001 for all). Serum total thyroxine (TT4), tri-iodothyronine, free T4 (FT4) by direct dialysis, nonesterified fatty acids (NEFA), and leptin were measured, and FT4 fraction (FFT4) was calculated. Serum thyrotropin (TSH) concentrations were measured in nine animals by validating a heterologous canine TSH assay with recombinant feline TSH as a standard. FT4, FFT4, NEFAs, and leptin were significantly higher in obese cats. FT4 had the strongest positive correlation with obesity indices BF, BMI, girth, NEFA, and leptin. Fatty acids oleate and palmitate were shown to inhibit T4 binding to pooled cat serum in vitro, suggesting the possibility that this mechanism was also relevant in vivo. Serum TT4 and TSH did not rise significantly. The implications for thyroid hormone (TH) action are not yet clear, but fatty acids have been proposed to inhibit the cellular uptake of TH and/or pituitary TH receptor binding, leading to TH resistance. Increased leptin may also alter sensitivity to negative feedback of TH. In conclusion, feline obesity is associated with a significant increase in FT4 within the normal range; future investigation into the cellular thyroid status will be necessary to establish cause and effect in this obesity model.

Download Full-text

The role of macrophages in osseointegration of dental implants: An experimental study in vivo

Journal of Biomedical Materials Research Part A ◽

10.1002/jbm.a.36978 ◽

2020 ◽

Vol 108 (11) ◽

pp. 2206-2216

Author(s):

Xin Wang ◽

Yu Li ◽

Yuan Feng ◽

Haode Cheng ◽

Dehua Li

Keyword(s):

Experimental Study ◽

Dental Implants

Download Full-text

Heart-type fatty acid-binding protein reciprocally regulates glucose and fatty acid utilization during exercise

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00287.2004 ◽

2005 ◽

Vol 288 (2) ◽

pp. E292-E297 ◽

Cited By ~ 16

Author(s):

Jane Shearer ◽

Patrick T. Fueger ◽

Jeffrey N. Rottman ◽

Deanna P. Bracy ◽

Bert Binas ◽

...

Keyword(s):

Fatty Acid ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Whole Body ◽

Metabolic Clearance ◽

Fatty Acid Binding ◽

Nonesterified Fatty Acids ◽

Acid Binding Protein

The role of heart-type cytosolic fatty acid-binding protein (H-FABP) in mediating whole body and muscle-specific long-chain fatty acid (LCFA) and glucose utilization was examined using exercise as a phenotyping tool. Catheters were chronically implanted in a carotid artery and jugular vein of wild-type (WT, n = 8), heterozygous (H-FABP+/−, n = 8), and null (H-FABP−/−, n = 7) chow-fed C57BL/6J mice, and mice were allowed to recover for 7 days. After a 5-h fast, conscious, unrestrained mice were studied during 30 min of treadmill exercise (0.6 mph). A bolus of [125I]-15-( p-iodophenyl)-3- R, S-methylpentadecanoic acid and 2-deoxy-[3H]glucose was administered to obtain rates of whole body metabolic clearance (MCR) and indexes of muscle LCFA (Rf) and glucose (Rg) utilization. Fasting, nonesterified fatty acids (mM) were elevated in H-FABP−/− mice (2.2 ± 0.9 vs. 1.3 ± 0.1 and 1.3 ± 0.2 for WT and H-FABP+/−). During exercise, blood glucose (mM) increased in WT (11.7 ± 0.8) and H-FABP+/− (12.6 ± 0.9) mice, whereas H-FABP−/− mice developed overt hypoglycemia (4.8 ± 0.8). Examination of tissue-specific and whole body glucose and LCFA utilization demonstrated a dependency on H-FABP with exercise in all tissues examined. Reductions in H-FABP led to decreasing exercise-stimulated Rf and increasing Rg with the most pronounced effects in heart and soleus muscle. Similar results were seen for MCR with decreasing LCFA and increasing glucose clearance with declining levels of H-FABP. These results show that, in vivo, H-FABP has reciprocal effects on glucose and LCFA utilization and whole body fuel homeostasis when metabolic demands are elevated by exercise.

Download Full-text

The peroxisomal transporter ABCD3 plays a major role in dicarboxylic fatty acid metabolism

10.1101/2021.07.26.452046 ◽

2021 ◽

Author(s):

Pablo Ranea-Robles ◽

Hongjie Chen ◽

Brandon Stauffer ◽

Chunli Yu ◽

Dipankar Bhattacharya ◽

...

Keyword(s):

Fatty Acids ◽

De Novo ◽

Ketone Bodies ◽

De Novo Lipogenesis ◽

Lipid Homeostasis ◽

Hepatic Cholesterol Synthesis ◽

Specific Subset

Peroxisomes metabolize a specific subset of fatty acids, which include dicarboxylic fatty acids (DCAs) generated by ω-oxidation. Data obtained in vitro suggest that the peroxisomal transporter ABCD3 (also known as PMP70) mediates the transport of DCAs into the peroxisome, but in vivo evidence to support this role is lacking. In this study, we studied an Abcd3 KO mouse model generated by CRISPR-Cas9 technology using targeted and untargeted metabolomics, histology, immunoblotting, and stable isotope tracing technology. We show that ABCD3 functions in DCA metabolism and uncover a novel role for this peroxisomal transporter in lipid metabolic homeostasis. The Abcd3 KO mouse presents with lipodystrophy, increased circulating free fatty acids, decreased ketone bodies, enhanced hepatic cholesterol synthesis and decreased hepatic de novo lipogenesis. Moreover, our study suggests that DCAs are metabolized by mitochondrial β-oxidation when ABCD3 is not functional, reflecting the importance of the metabolic compartmentalization and communication between peroxisomes and mitochondria. In summary, this study provides data on the role of the peroxisomal transporter ABCD3 in hepatic lipid homeostasis and DCA metabolism, and the consequences of peroxisomal dysfunction for the liver.

Download Full-text

Role of adipokines and nonesterified fatty acids in the development of insulin resistance

Problems of Endocrinology ◽

10.14341/probl200955313-16 ◽

2009 ◽

Vol 55 (3) ◽

pp. 13-16 ◽

Cited By ~ 1

Author(s):

D. A. Tanyanskiy ◽

E M. Firova ◽

L. V. Shatilina ◽

A. D. Denisenko

Keyword(s):

Insulin Resistance ◽

Fatty Acids ◽

Body Weight ◽

Adipose Tissue ◽

Regression Analysis ◽

Linear Regression Analysis ◽

Biologically Active ◽

Homa Index ◽

Nonesterified Fatty Acids

The purpose of the study was to reveal a possible role of adipokines, biologically active adipose tissue proteins (leptin and adiponectin) and nonesterified fatty acids in generating insulin resistance (IR). One hundred and fifty-seven patients (90 females and 67 males) aged 57.5±9.2 years were enrolled in the study. According to the HOMA index for IR, the patients were divided into 3 equal groups. The examinees with a high HOMA index were found to have elevated levels of fatty acids, leptin and decreased concentrations of adiponectin. At the same time according to the linear regression analysis, all these indices are its independent determinants. However, analysis of the data in the groups of patients with different body weight revealed that the increased concentrations of fatty acids and leptin may play a role in the development of IR in subjects with obesity while the higher level of fatty acids and lower adiponectin may be involved in patients without noticeable obesity. Thus, it may be assumed that leptin, adiponectin and nonesterified fatty acids may affect the development of IR; however, their contribution depends on the degree of adiposity.

Download Full-text

Plasmalogens: targets for oxidants and major lipophilic antioxidants

Biochemical Society Transactions ◽

10.1042/bst0320147 ◽

2004 ◽

Vol 32 (1) ◽

pp. 147-150 ◽

Cited By ~ 108

Author(s):

B. Engelmann

Keyword(s):

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Lipid Oxidation ◽

De Novo ◽

Peroxyl Radicals ◽

Plasma Lipoproteins ◽

Future Work

Cellular membranes and plasma lipoproteins are less efficiently protected against oxidative stress than the various aqueous compartments of mammalian organisms. Here, previous results on the role of plasmalogens in lipid oxidation are evaluated on the basis of criteria required for an antioxidant. The plasmalogen-specific enol ether double bond is targeted by a vast variety of oxidants, including peroxyl radicals, metal ions, singlet oxygen and halogenating species. Oxidation of the vinyl ether markedly prevents the oxidation of highly polyunsaturated fatty acids, and products of plasmalogen degradation do not propagate lipid oxidation. This protection is also demonstrated intramolecularly, thus ascertaining the function of plasmalogens as a major storage pool for polyunsaturated fatty acids. Although cells rapidly incorporate and synthesize plasmalogens de novo, their plasmalogen contents can be deliberately increased by supplementation with precursors. Thus plasmalogens terminate lipid-oxidation processes, are present in adequate locations at sufficient concentrations, and are rapidly regenerated, classifying them as efficient antioxidants in vitro. Future work should address the in vivo role of plasmalogens in lipid oxidation and the biological function of plasmalogen interactions with oxidants.

Download Full-text