scholarly journals MH-76, a Novel Non-Quinazoline α1-Adrenoceptor Antagonist, but Not Prazosin Reduces Inflammation and Improves Insulin Signaling in Adipose Tissue of Fructose-Fed Rats

2021 ◽  
Vol 14 (5) ◽  
pp. 477
Author(s):  
Monika Kubacka ◽  
Szczepan Mogilski ◽  
Monika Zadrożna ◽  
Barbara Nowak ◽  
Małgorzata Szafarz ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Signaling ◽  
Inflammatory Cells ◽  
Lipid Lowering ◽  
Adrenoceptor Antagonist ◽  
First Line Therapy ◽  
Distribution Studies ◽  
Immunohistochemical Studies ◽  
Endothelial Integrity ◽  
Apoptosis And Necrosis

Background: Quinazoline α1-adrenoceptors antagonists have been shown to exert moderately favorable effects on the metabolic profile in hypertensive patients. However, based on AntiHypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) results, they are no longer recommended as a first line therapy of hypertension. Recent studies have shown that quinazoline-based α1-adrenoceptors antagonists (prazosin, doxazosin) induce the apoptosis and necrosis, which may be responsible for ALLHAT outcomes; however, these effects were proven to be independent of α1-adrenoceptor blockade and were associated with the presence of quinazoline moiety. MH-76 (1-[3-(2,6-dimethylphenoxy)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride)) is a non-quinazoline α1-adrenoceptor antagonist which, in fructose-fed rats, exerted antihypertensive effect, and, contrary to prazosin, reduced insulin resistance and abdominal adiposity. In this study we aimed to further investigate and compare the effects of MH-76 and prazosin on inflammation in adipose tissue of fructose-fed rats. Methods: Abdominal adipose tissue was collected from four groups of fructose-fed rats (Control, Fructose, Fructose + MH-76 and Fructose + Prazosin) and subjected to biochemical, histopathological and immunohistochemical studies. Moreover, selected tissue distribution studies were performed. Results: Treatment with MH-76 but not with prazosin improved endothelial integrity, reduced adipose tissue inflammation and infiltration by immune cells, resulting in lowering leptin, MCP-1, IL-6, TNF-α and PAI-1 levels. In adipose tissue from Fructose + MH-76 animals, a higher amount of eosinophils accompanied with higher IL-4 concentration was observed. Treatment with MH-76 but not with prazosin markedly reduced phosphorylation of IRS-1 at Ser307. Conclusion: MH-76 may improve insulin signaling in adipose tissue by reducing the pro-inflammatory cytokine production and inhibiting the inflammatory cells recruitment. In contrast, in adipose tissue from animals treated with prazosin, the inflammatory effect was clearly enhanced.

scholarly journals Methionine and Arginine Supply Alters Abundance of Amino Acid, Insulin Signaling, and Glutathione Metabolism-Related Proteins in Bovine Subcutaneous Adipose Explants Challenged with N-Acetyl-d-sphingosine

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2114
Author(s):  
Yusheng Liang ◽  
Nana Ma ◽  
Danielle N. Coleman ◽  
Fang Liu ◽  
Yu Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Amino Acid ◽  
Insulin Signaling ◽  
Elongation Factor ◽  
In Vivo Studies ◽  
Glutathione Metabolism ◽  
Protein Abundance ◽  
Related Proteins ◽  
Subcutaneous Adipose

The objective was to perform a proof-of-principle study to evaluate the effects of methionine (Met) and arginine (Arg) supply on protein abundance of amino acid, insulin signaling, and glutathione metabolism-related proteins in subcutaneous adipose tissue (SAT) explants under ceramide (Ce) challenge. SAT from four lactating Holstein cows was incubated with one of the following media: ideal profile of amino acid as the control (IPAA; Lys:Met 2.9:1, Lys:Arg 2:1), increased Met (incMet; Lys:Met 2.5:1), increased Arg (incArg; Lys:Arg 1:1), or incMet plus incArg (Lys:Met 2.5:1 Lys:Arg 1:1) with or without 100 μM exogenous cell-permeable Ce (N-Acetyl-d-sphingosine). Ceramide stimulation downregulated the overall abundance of phosphorylated (p) protein kinase B (AKT), p-mechanistic target of rapamycin (mTOR), and p-eukaryotic elongation factor 2 (eEF2). Without Ce stimulation, increased Met, Arg, or Met + Arg resulted in lower p-mTOR. Compared with control SAT stimulated with Ce, increased Met, Arg, or Met + Arg resulted in greater activation of mTOR (p-mTOR/total mTOR) and AKT (p-AKT/total AKT), with a more pronounced response due to Arg. The greatest protein abundance of glutathione S-transferase Mu 1 (GSTM1) was detected in response to increased Met supply during Ce stimulation. Ceramide stimulation decreased the overall protein abundance of the Na-coupled neutral amino acid transporter SLC38A1 and branched-chain alpha-ketoacid dehydrogenase kinase (BCKDK). However, compared with controls, increased Met or Arg supply attenuated the downregulation of BCKDK induced by Ce. Circulating ceramides might affect amino acid, insulin signaling, and glutathione metabolism in dairy cow adipose tissue. Further in vivo studies are needed to confirm the role of rumen-protected amino acids in regulating bovine adipose function.

scholarly journals Xylo-Oligosaccharides in Prevention of Hepatic Steatosis and Adipose Tissue Inflammation: Associating Taxonomic and Metabolomic Patterns in Fecal Microbiomes with Biclustering

2021 ◽  
Vol 18 (8) ◽  
pp. 4049
Author(s):  
Jukka Hintikka ◽  
Sanna Lensu ◽  
Elina Mäkinen ◽  
Sira Karvinen ◽  
Marjaana Honkanen ◽  
...  
Keyword(s):  
Amino Acids ◽  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
Insulin Signaling ◽  
Aromatic Amino Acids ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Beneficial Effects ◽  
Male Wistar Rats ◽  
Branched Chain

We have shown that prebiotic xylo-oligosaccharides (XOS) increased beneficial gut microbiota (GM) and prevented high fat diet-induced hepatic steatosis, but the mechanisms associated with these effects are not clear. We studied whether XOS affects adipose tissue inflammation and insulin signaling, and whether the GM and fecal metabolome explain associated patterns. XOS was supplemented or not with high (HFD) or low (LFD) fat diet for 12 weeks in male Wistar rats (n = 10/group). Previously analyzed GM and fecal metabolites were biclustered to reduce data dimensionality and identify interpretable groups of co-occurring genera and metabolites. Based on our findings, biclustering provides a useful algorithmic method for capturing such joint signatures. On the HFD, XOS-supplemented rats showed lower number of adipose tissue crown-like structures, increased phosphorylation of AKT in liver and adipose tissue as well as lower expression of hepatic miRNAs. XOS-supplemented rats had more fecal glycine and less hypoxanthine, isovalerate, branched chain amino acids and aromatic amino acids. Several bacterial genera were associated with the metabolic signatures. In conclusion, the beneficial effects of XOS on hepatic steatosis involved decreased adipose tissue inflammation and likely improved insulin signaling, which were further associated with fecal metabolites and GM.

Insulin signaling in adipose tissue of patients with primary aldosteronism

2011 ◽  
Vol 34 (2) ◽  
pp. 86-89
Author(s):  
R. Urbanet ◽  
C. Pilon ◽  
F. Giorgino ◽  
R. Vettor ◽  
F. Fallo
Keyword(s):  
Adipose Tissue ◽  
Insulin Signaling ◽  
Primary Aldosteronism

Plasma Lipid-lowering and Lipogenesis-stimulating Actions of Ginseng Saponins in Tumor-bearing Rats

1983 ◽  
Vol 11 (01n04) ◽  
pp. 88-95 ◽  
Author(s):  
Masahiro Yamamoto ◽  
Akira Kumagai ◽  
Yuichi Yamamura
Keyword(s):  
Adipose Tissue ◽  
Oral Administration ◽  
Plasma Cholesterol ◽  
Lipid Fraction ◽  
Plasma Lipid ◽  
Male Rats ◽  
Lipid Lowering ◽  
Tumor Bearing ◽  
Saponin Content

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.

Lipid Lowering Therapy and Stabilization of Atherosclerotic Plaques

1999 ◽  
Vol 82 (S 01) ◽  
pp. 60-61 ◽  
Author(s):  
Dirk Müller-Wieland ◽  
Wilhelm Krone
Keyword(s):  
Thrombus Formation ◽  
Inflammatory Cells ◽  
Cardiovascular Complications ◽  
Lipid Lowering ◽  
Atherosclerotic Plaques ◽  
Lipid Lowering Therapy ◽  
New Paradigm ◽  
Clinical Prognosis ◽  
Fibrous Cap ◽  
Lowering Therapy

SummaryLipid-lowering therapy leads to a great reduction of cardiovascular complications, but has almost no effect on the degree of stenosis of coronary arteries. These and other studies have lead to a new paradigm of coronary artery disease, i. e. clinical prognosis is not only determined by the extent of a single stenosis, but mainly by the number and structure of atherosclerotic plaques. Rupture of an instable or vulnerable plaque, characterized by a large lipid-rich central core, inflammatory cells, and a thin fibrous cap, causes sudden thrombus formation and thereby acute coronary syndromes. There is accumulating evidence that cholesterol lowering can result in plaque stabilization and improvement of endothelial dysfunction.

scholarly journals The role of miR‐146a‐5p on insulin signaling and inflammation in adipose tissue of longliving Ames dwarf mice.

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Allancer Divino De Carvalho Nunes ◽  
Lin Yu ◽  
Collin Lahde ◽  
Sarah Noureddine ◽  
Tatiana Saccon ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Signaling ◽  
Ames Dwarf Mice ◽  
Ames Dwarf ◽  
Dwarf Mice

scholarly journals Inflammatory cells in perivascular adipose tissue and the integrity of the tunica media in atherosclerotic coronary arteries

2019 ◽  
Author(s):  
Ruda Zorc-Pleskovič ◽  
Marjeta Zorc ◽  
Dušan Šuput ◽  
Aleksandra Milutinović
Keyword(s):  
Adipose Tissue ◽  
Coronary Arteries ◽  
Obstructive Coronary Artery Disease ◽  
Inflammatory Cells ◽  
Elastic Membrane ◽  
Inflammatory Infiltration ◽  
Perivascular Adipose Tissue ◽  
Tunica Media ◽  
External Elastic Membrane ◽  
The Media

Obstructive coronary artery disease (CAD) is characterized by inflammation within the atherosclerotic coronary arteries. Infiltration of inflammatory cells into muscular media can lead to remodeling and weakening of the arterial wall. We examined the relationship between inflammatory infiltration in perivascular adipose tissue (PVAT), state of the external elastic membrane, and the intensity of inflammatory infiltration in the tunica media of coronary arteries obtained by endarterectomy from symptomatic patients with diffuse CAD. We analyzed endarterectomy sequesters from 22 coronary arteries that contained the intima, media, a part of the adventitia, and PVAT in at least one part of the sequester. The coronary arteries were divided into two groups according to the presence or absence of inflammatory infiltration in PVAT. Staining with hematoxylin-eosin and by the Movat's method showed atherosclerotic changes in the intima and media. Immunohistochemistry (anti-leukocyte common antigen [LCA] antibody) was used for the detection of leukocytes. We found a significant positive correlation between inflammatory infiltration in PVAT and preservation of the external elastic membrane of coronary arteries. Furthermore, we found a significant negative correlation between inflammatory infiltration in PVAT and the intensity of inflammatory infiltration in the media. It seems that the integrity of the external elastic membrane and the proinflammatory properties of PVAT restrain inflammatory cells within PVAT. Both effects may prevent the migration of inflammatory cells into the media and delay the development of CAD.

scholarly journals Epicardial adipose tissue volume and coronary calcification among people living with diabetes: a cross-sectional study

2020 ◽  
Author(s):  
Emmanuel Cosson ◽  
Minh Tuan Nguyen ◽  
Imen Rezgani ◽  
Sopio Tatulashvili ◽  
Meriem Sal ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Epicardial Adipose Tissue ◽  
Multivariable Analysis ◽  
Hdl Cholesterol ◽  
Macrovascular Disease ◽  
Coronary Calcification ◽  
Lipid Lowering ◽  
Smoking History ◽  
Cross Sectional ◽  
Patients With Diabetes

Abstract Background Epicardial adipose tissue (EAT) has anatomic and functional proximity to the heart and is considered a novel diagnostic marker and therapeutic target in cardiometabolic diseases. The aim of this study was to evaluate whether EAT volume was associated with coronary artery calcification (CAC) in people living with diabetes, independently of confounding factors.Methods We included all consecutive patients with diabetes whose EAT volume and CAC score were measured using computed tomography between January 1, 2019 and September 30, 2020 in the Department of Diabetology-Endocrinology-Nutrition at Avicenne Hospital, France. Determinants of EAT volume and a CAC score ≥ 100 Agatston units (AU) were evaluated.Results The study population comprised 409 patients (218 men). Mean (± standard deviation) age was 57 ± 12 years, and 318, 56 and 35, had type 2 (T2D), type 1 (T1D), or another type of diabetes, respectively. Mean body mass index (BMI) was 29 ± 6 kg/m², mean AET volume 93 ± 38 cm3. EAT volume was positively correlated with age, BMI, pack-year smoking history and triglyceridaemia, but negatively correlated with HDL-cholesterol level. Furthermore, it was lower in people with retinopathy, but higher in men, in Caucasian people, in patients on antihypertensive and lipid-lowering medication, in people with nephropathy, and finally in individuals with a CAC ≥ 100 AU (CAC < 100 vs CAC ≥ 100: 89 ± 35 vs 109 ± 41 cm3, respectively, p < 0.05). In addition to EAT volume, other determinants of CAC ≥ 100 AU (n = 89, 22%) were age, T2D, ethnicity, antihypertensive and lipid-lowering medication, cumulative tobacco consumption, retinopathy, macular edema and macrovascular disease. Multivariable analysis considering all these determinants as well as gender and BMI, showed that EAT volume was independently associated with CAC ≥ 100 AU (per 10 cm3 increase: OR 1.11 [1.02–1.20]).Conclusions EAT volume was independently associated with CAC. As it may play a role in coronary atherosclerosis in patients with diabetes, reducing EAT volume through physical exercise, improved diet and pharmaceutical interventions may improve future cardiovascular risk outcomes in this population.

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