MH-76, a Novel Non-Quinazoline α

adipocytokines adipose tissue fructose-fed rats inflammation insulin resistance metabolic syndrome obesity α1-adrenoceptors antagonist

Journal

Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453

Informations de publication

Date de publication:
18 May 2021
Historique:
received: 29 03 2021
revised: 09 05 2021
accepted: 12 05 2021
entrez: 2 6 2021
pubmed: 3 6 2021
medline: 3 6 2021
Statut: epublish

Résumé

Quinazoline α 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. 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. 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.

Sections du résumé

BACKGROUND BACKGROUND
Quinazoline α
METHODS 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 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 CONCLUSIONS
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.

Identifiants

pubmed: 34069933
pii: ph14050477
doi: 10.3390/ph14050477
pmc: PMC8157569
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : National Science Centre
ID : DEC-2014/15/D/NZ7/01807

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Auteurs

Monika Kubacka (M)

Department of Pharmacodynamics, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland.

Szczepan Mogilski (S)

Department of Pharmacodynamics, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland.

Monika Zadrożna (M)

Department of Cytobiology, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland.

Barbara Nowak (B)

Department of Cytobiology, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland.

Małgorzata Szafarz (M)

Department of Pharmacokinetics and Physical Pharmacy, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland.

Bartosz Pomierny (B)

Department of Biochemical Toxicology, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland.

Henryk Marona (H)

Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland.

Anna Waszkielewicz (A)

Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland.

Wojciech Jawień (W)

Department of Pharmaceutical Biophysics, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland.

Jacek Sapa (J)

Department of Pharmacodynamics, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland.

Marek Bednarski (M)

Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University, Medical College, 9 Medyczna Street, 30-688 Kraków, Poland.

Joanna Knutelska (J)

Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University, Medical College, 9 Medyczna Street, 30-688 Kraków, Poland.

Magdalena Kotańska (M)

Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University, Medical College, 9 Medyczna Street, 30-688 Kraków, Poland.

Classifications MeSH