Chronic benzylamine administration in the drinking water improves glucose tolerance, reduces body weight gain and circulating cholesterol in high-fat diet-fed mice.
Benzylamine is found in Moringa oleifera, a plant used to treat diabetes in traditional medicine. In mammals, benzylamine is metabolized by semicarbazide-sensitive amine oxidase (SSAO) to benzaldehyde and hydrogen peroxide. This latter product has insulin-mimicking action, and is involved in the effects of benzylamine on human adipocytes: stimulation of glucose transport and inhibition of lipolysis. This study examined whether chronic, oral administration of benzylamine could improve glucose tolerance and the circulating lipid profile without increasing oxidative stress in overweight and pre-diabetic mice. The benzylamine diffusion across the intestine was verified using everted gut sacs. Then, glucose handling and metabolic markers were measured in mice rendered insulin-resistant when fed a high-fat diet (HFD) and receiving or not benzylamine in their drinking water (3600micromol/(kgday)) for 17 weeks. HFD-benzylamine mice showed lower body weight gain, fasting blood glucose, total plasma cholesterol and hyperglycaemic response to glucose load when compared to HFD control. In adipocytes, insulin-induced activation of glucose transport and inhibition of lipolysis remained unchanged. In aorta, benzylamine treatment partially restored the nitrite levels that were reduced by HFD. In liver, lipid peroxidation markers were reduced. Resistin and uric acid, surrogate plasma markers of metabolic syndrome, were decreased. In spite of the putative deleterious nature of the hydrogen peroxide generated during amine oxidation, and in agreement with its in vitro insulin-like actions found on adipocytes, the SSAO-substrate benzylamine could be considered as a potential oral agent to treat metabolic syndrome.
Iffiú-Soltész
Zsuzsa
Z
INSERM, U858, Institut de Médecine Moléculaire de Rangueil, IFR 150, Toulouse, France.
Wanecq
Estelle
E
Lomba
Almudena
A
Portillo
Maria P
MP
Pellati
Federica
F
Szöko
Eva
E
Bour
Sandy
S
Woodley
John
J
Milagro
Fermin I
FI
Alfredo Martinez
J
J
Valet
Philippe
P
Carpéné
Christian
C
D017667:Adipocytes / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001596:Benzylamines / Q000008:administration & dosage* / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D006861:Hydrogen Peroxide / Q000009:adverse effects; D006943:Hyperglycemia / Q000188:drug therapy*; D066298:In Vitro Techniques; D007333:Insulin Resistance; D015227:Lipid Peroxidation / Q000187:drug effects; D008066:Lipolysis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009573:Nitrites / Q000378:metabolism; D052243:Resistin / Q000097:blood; D014527:Uric Acid / Q000097:blood; D015430:Weight Gain / Q000187:drug effects*
D001596:Benzylamines; D001786:Blood Glucose; D009573:Nitrites; D052243:Resistin; D014527:Uric Acid; D002784:Cholesterol; C030796:benzylamine; D006861:Hydrogen Peroxide