Long chain polyunsaturated fatty acids (LCPUFAs) and nordihydroguaiaretic acid (NDGA) modulate metabolic and inflammatory markers in a spontaneous type 2 diabetesmellitus model (Stillman Salgado rats)

DÍAZ-GEREVINI GUSTAVO; GASTON REPOSSI; ALEJANDRO DAIN; ALDO RENATO EYNARD

LIPIDS IN HEALTH AND DISEASE

BIOMED CENTRAL LTD

Año: 2016 vol. 15 p. 1 - 15

1476-511X

AbstractBackground: Diabetes mellitus (DM) is a complex disease with alterations in metabolic and inflammatory markers.Stillman Salgado rats (eSS) spontaneously develop type 2 DM by middle age showing progressive impairment ofglucose tolerance with hyperglycemia, hypertriglyceridemia and hyperinsulinemia. We analyzed the effects ofsupplementation of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) with or without nordihydroguaiaretic acid(NDGA) added, an antioxidant and lipoxygenase inhibitor, on metabolic and inflammatory parameters in eSS rats toevaluate whether they can delay development and/or prevent progression of DM.Methods: After weaning, eSS rats received, intraperitoneally, once a month ω-3 (EPA 35% and DHA 40%?6.25mg/Kg) or ω-6(90% arachidonic acid- 6. 25 mg/Kg) for twelvemonths. Two additional groups of rats received 1.9 mg/kg NDGA added to ω-3and ω-6 fatty acids. Blood samples were collected at day 40, and at the end of the 6thmonth and 12thmonth of age todetermine plasma triglycerides (TGs), total plasma fatty acids (FA), A1C hemoglobin (HbA1C), C-reactive protein (CRP), gammaglutamyl transpeptidase (GGT), lipo and hydro peroxides, nitrites and IL-6 (in plasma and liver, kidney, and pancreas) andunderwent oral glucose tolerance test (OGTT) as well. Wistar and eSS rats that received saline solution were used as controls.Results: Plasma lipids profile, TG, fasting and post-prandial blood glucose levels, and glycosylated HbA1C showed significantimprovements in ω-3 and ω-3 + NDGA treated animals compared to eSS control group. ω-3 and ω-3 + NDGA groups showedan inverse correlation with fasting blood glucose and showed lower plasma levels of GGT, TG, and CRP. eSS rats treated with ω-3 LCPUFAs showed reduced level of inflammatory and oxidative indices in plasma and liver, kidney and pancreas tissues incomparison with eSS control (non-treated) and ω-6 treated groups.Conclusions: eSS rats are a useful model to study type 2 DM pathophysiology and related inflammatory indices. ω-3 +NDGA supplementation, at the doses tested, ameliorated inflammatory, metabolic and oxidative stress markers studied.