Kupffer cell-derived prostaglandin E<sub>2</sub>is involved in alcohol-induced fat accumulation in rat liver

Enomoto, Nobuyuki; Ikejima, Kenichi; Yamashina, Shunhei; Enomoto, Akiko; Nishiura, Teruhiro; Nishimura, Tetsuro; Brenner, David A.; Schemmer, Peter; Bradford, Blair U.; Rivera, Chantal A.; Zhong, Zhi; Thurman, Ronald G.

doi:10.1152/ajpgi.2000.279.1.g100

Cited by 116 publications

(93 citation statements)

References 32 publications

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“…The concentrations of plasma PGE 2 decreased immediately after calving in both groups, however, suggesting suppression of PGE 2 production from macrophages. In other research, PGE 2 administered intravenously to rats was associated with hepatic lipidosis (Enomoto et al 2000). Therefore, a decrease in the concentration of plasma PGE 2 immediately after parturition might be beneficial to transition cows.…”

Section: Discussionmentioning

confidence: 87%

Strong relationships between mediators of the acute phase response and fatty liver in dairy cows

Ametaj¹,

Bradford²,

Bobe³

et al. 2005

Can. J. Anim. Sci.

152

126

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. 2005. Strong relationships between mediators of the acute phase response and fatty liver in dairy cows. Can. J. Anim. Sci. 85: [165][166][167][168][169][170][171][172][173][174][175]. The objective of this study was to investigate the relationship between activation of acute phase response and fatty liver in transition dairy cows. Fatty liver was induced in dairy cows by feeding 8 kg of cracked corn 1 mo before the expected day of parturition. Liver and blood samples were obtained at days -4, 3, 8, 12, 14, 22, 27, and 36 postpartum. Cows that developed fatty liver (n = 4) reached peak total lipids in the liver at day 12 postpartum with 11.4% (wet wt.) compared with 6.6% in control cows (n = 4). Cows with fatty liver had greater plasma tumor necrosis factor-alpha (TNF-α), nonesterified fatty acids (NEFA), and lower lactate concentrations than did control cows at day -4. During highest concentrations of total lipids in the liver, for at least one time-point, fatty-liver cows had greater concentrations of plasma serum amyloid A (SAA), haptoglobin, and NEFA and lower concentrations of calcitonin gene-related peptide (CGRP), prostaglandin E 2 (PGE 2 ), cortisol, and TNF-α than did control cows. Concentrations of total lipids in the liver at 12 d postpartum were correlated (a) positively with plasma TNF-α, SAA, and NEFA and negatively with plasma CGRP before calving, (b) positively with plasma SAA, haptoglobin, and NEFA and negatively with plasma PGE 2 , CGRP, total cholesterol, and glucose at days 3, 8, and 12 postpartum, and (c) negatively with concentrations of plasma glucose, lactate, and total bilirubin after day 12 postpartum. In conclusion, this study indicates that the acute phase response occurs in cows with fatty liver as well as strong relationships between mediators of immune response and fatty liver. Mots clés: Réponse phase aiguë, foie gras, vaches laitièresFatty liver is a common metabolic disorder that affects almost half of all dairy cows immediately after parturition.Despite much progress in understanding metabolic events during the development of fatty liver, the precise mechanisms of the pathology remain unclear. The conventional view is that fatty liver is characterized by excess liver triacylglycerols (TAG) arising from a negative energy balance after parturition (Bauchart et al. 1998). The negative energy balance evokes a major mobilization of non-esterified fatty acids (NEFA) from adipose tissue and increased uptake of

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Section: Discussionmentioning

confidence: 87%

Strong relationships between mediators of the acute phase response and fatty liver in dairy cows

Ametaj¹,

Bradford²,

Bobe³

et al. 2005

Can. J. Anim. Sci.

152

126

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“…127 In this regard, PGE 2 also inhibits liver lipolysis, b-oxidation, and very low density lipoprotein synthesis further contributing to obesity, 128 yet the EP receptor is unknown. This lipid-accumulating effect of PGE 2 on hepatocyte lipid metabolism has been recognized for quite some time [129][130][131][132][133][134] ; however, it has also been demonstrated that PGE 2 derived from nonparenchymal liver cells attenuates insulin responses in the hepatocyte. 124 COX-2 derived PGE 2 also inhibits pancreatic insulin secretion, and COX-2 inhibitors and EP 3 antagonists improved b-cell function in mice, resulting in enhanced insulin release and glucose tolerance after a glucose challenge.…”

Section: Pge 2 In Other Aspects Of the Metabolic Syndromementioning

confidence: 99%

PGE2, Kidney Disease, and Cardiovascular Risk

Nasrallah

Hassouneh

Hébert

2016

Journal of the American Society of Nephrology

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An important measure of cardiovascular health is obtained by evaluating the global cardiovascular risk, which comprises a number of factors, including hypertension and type 2 diabetes, the leading causes of illness and death in the world, as well as the metabolic syndrome. Altered immunity, inflammation, and oxidative stress underlie many of the changes associated with cardiovascular disease, diabetes, and the metabolic syndrome, and recent efforts have begun to elucidate the contribution of PGE 2 in these events. This review summarizes the role of PGE 2 in kidney disease outcomes that accelerate cardiovascular disease, highlights the role of cyclooxygenase-2/microsomal PGE synthase 1/PGE 2 signaling in hypertension and diabetes, and outlines the contribution of PGE 2 to other aspects of the metabolic syndrome, particularly abdominal adiposity, dyslipidemia, and atherogenesis. A clearer understanding of the role of PGE 2 could lead to new avenues to improve therapeutic options and disease management strategies. 27: 666-676, 201627: 666-676, . doi: 10.1681 Accelerated cardiovascular disease is the leading cause of mortality in patients with kidney disease. 1,2 This implies that kidney disease has a major effect on global cardiovascular risk, affecting fluid (volume, BP), electrolyte, and acid base balance, among many other cardiovascular risk factors. In fact, renal transplantation ameliorates cardiovascular risk, improves quality of life, and reduces mortality. 2 PGs are important homeostatic regulators of kidney function. PGE 2 is the major product of cyclooxygenase (COX)-2 and microsomal PGE synthase 1 (mPGES1), and both of these enzymes are elevated in renal diseases. [3][4][5][6][7][8][9][10] PGE 2 binds four EP receptors (EP 1-4 ) to activate G protein signaling responses. Figure 1 illustrates the COX pathway leading to PGE 2 , as well as its target receptors. These receptors are often coexpressed in cells and usually have opposing effects (protective and harmful). PGE 2 acting on EP can alter vascular tone and influence renal blood flow and hemodynamics. 11-15 PGE 2 also stimulates the macula densa to activate the renin-angiotensin-aldosterone system, a key mediator of kidney injury. [16][17][18][19] Inflammatory, immune, and oxidative stress responses are influenced by PGE 2 , which are reported to alter growth, fibrosis, and apoptosis in renal cells. 20-26 PGE 2 also contributes to disturbances in collecting duct salt and water transport in polyuric diseases, 19,[27][28][29] and b cell defects in sodium and potassium handling associated with type I distal renal tubule acidosis. 30 PGE 2 /EP 4 also compensates for the loss of vasopressin V2 receptors in mouse diabetes insipidus. 28 Although attempts to block PGE 2 using COX-2 or mPGES1 inhibitors have failed, selective inhibition of EP receptors may prove to be quite useful in controlling the deleterious effects of COX-2/mPGES1/PGE 2 , while leaving the protective responses intact. EP 1 mediates many of the pathologic effects of PGE 2 in kidne...

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“…Furthermore, Kupffer cell-derived PGE2 has been implicated in alcohol-induced steatosis in rat liver ( 40 ). Despite their importance to hepatic lipid metabolism, little is known about the factors regulating PG production.…”

Section: Cd36 Deletion Alters Vldl Secretion and Pg Levels In Ob/ob Lmentioning

confidence: 99%

CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice

Nassir

Adewole

Brunt

et al. 2013

Journal of Lipid Research

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This article is available online at http://www.jlr.org novo FA synthesis or de novo lipogenesis (DNL), decreased FA oxidation, and reduced secretion of VLDLs ( 1, 2 ).CD36 is a class B scavenger receptor that plays an important role in several pathways of FA utilization. The protein is expressed in many cell types, including lingual taste bud cells, enterocytes, adipocytes, myocytes, and immune cells. On taste bud cells, CD36 is important for FA recognition and fat perception ( 3, 4 ). In skeletal muscle, heart, and adipose tissue, CD36 facilitates tissue FA uptake and utilization ( 5, 6 ). In the small intestine, it is important for chylomicron secretion ( 7 ) and for FA-induced release of secretin and cholecystokinin ( 8 ). In the liver, CD36 is expressed on endothelial, parenchymal, and Kupffer cells ( 9 ). Basal expression of liver CD36 is low but increases in experimental models of hepatic steatosis, such as genetic obesity and highfat feeding ( 10, 11 ) or following activation of the prosteatotic transcription factors liver X receptor (LXR), pregnane X receptor (PXR), and aryl hydrocarbon receptor (AHR) by xenobiotics, bacteria, or cytokines ( 12 ). Mice fed a highfat diet have increased liver CD36 expression associated with enhanced hepatic FA uptake and TG accumulation, and these are prevented by CD36 deletion ( 11 ). Interestingly, however, the prosteatotic effects of a high-fructose diet, which enhances DNL and TG accumulation in the liver ( 13 ), are exacerbated by CD36 deletion ( 14 ).In humans with nonalcoholic fatty liver disease (NAFLD), hepatic CD36 positively correlates with liver fat content ( 15 ), but its relationship to output of VLDL suggests that its impact on hepatic FA metabolism might not be limited to enhancing FA fl ux and TG accumulation. NAFLD is Abstract Recent findings described the role of CD36-mediated signaling in regulating cellular calcium and the release of various bioactive molecules, including the prostaglandins, neurotransmitters, cholecystokinin, and secretin. Here we document the role of CD36 in the secretion of hepatic VLDL. CD36 deletion resulted in 60% suppression of VLDL output in vivo, and VLDL secretion was reduced in vitro using incubated liver slices. The effect of CD36 deletion was mediated by enhancing formation of hepatic prostaglandins D2, F2, and E2. Treatment of CD36-defi cient slices with inhibitors of cyclooxygenases reversed the reduction in triglyceride secretion. We also examined the effect of CD36 deletion on the obesity-associated spontaneous steatosis of the ob/ob mouse that is driven by enhanced de novo lipogenesis. Homozygous ob/ob mice lacking CD36 ( ob-CD36 ؊ / ؊ ) were generated and studied for hepatic triglyceride accumulation and VLDL secretion. Livers of ob/ob mice were steatotic as expected and had 5-fold more CD36 on Kupffer cells and hepatocytes. CD36 deletion exacerbated the steatosis by impairing hepatic triglyceride and apoB secretion through increasing prostaglandin levels. These fi ndings suggest an unappreciated role of CD36 in reg...

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Kupffer cell-derived prostaglandin E₂is involved in alcohol-induced fat accumulation in rat liver

Cited by 116 publications

References 32 publications

Strong relationships between mediators of the acute phase response and fatty liver in dairy cows

Strong relationships between mediators of the acute phase response and fatty liver in dairy cows

PGE2, Kidney Disease, and Cardiovascular Risk

CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice

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Kupffer cell-derived prostaglandin E2is involved in alcohol-induced fat accumulation in rat liver

Cited by 116 publications

References 32 publications

Strong relationships between mediators of the acute phase response and fatty liver in dairy cows

Strong relationships between mediators of the acute phase response and fatty liver in dairy cows

PGE2, Kidney Disease, and Cardiovascular Risk

CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice

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Kupffer cell-derived prostaglandin E₂is involved in alcohol-induced fat accumulation in rat liver