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

Abstract

BackgroundDiabetes 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 of glucose tolerance with hyperglycemia, hypertriglyceridemia and hyperinsulinemia. We analyzed the effects of supplementation 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 to evaluate whether they can delay development and/or prevent progression of DM.MethodsAfter weaning, eSS rats received, intraperitoneally, once a month ω-3 (EPA 35% and DHA 40%–6.25 mg/Kg) or ω-6 (90% arachidonic acid- 6. 25 mg/Kg) for twelve months. Two additional groups of rats received 1.9 mg/kg NDGA added to ω-3 and ω-6 fatty acids. Blood samples were collected at day 40, and at the end of the 6th month and 12th month of age to determine plasma triglycerides (TGs), total plasma fatty acids (FA), A1C hemoglobin (HbA1C), C-reactive protein (CRP), gamma glutamyl transpeptidase (GGT), lipo and hydro peroxides, nitrites and IL-6 (in plasma and liver, kidney, and pancreas) and underwent oral glucose tolerance test (OGTT) as well. Wistar and eSS rats that received saline solution were used as controls.ResultsPlasma lipids profile, TG, fasting and post-prandial blood glucose levels, and glycosylated HbA1C showed significant improvements in ω-3 and ω-3 + NDGA treated animals compared to eSS control group. ω-3 and ω-3 + NDGA groups showed an 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 in comparison with eSS control (non-treated) and ω-6 treated groups.ConclusionseSS 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.

Diabetic encephalopathy: beneficial effects of supplementation with fatty acids ω3 and nordihydroguaiaretic acid in a spontaneous diabetes rat model

“…On the other hand, those animals administered with ω3 exhibited lower values of this ratio, similar to non-diabetic Wistar rats, which showed further decrease when NDGA was added. These findings suggest that low doses of fish oil when given for a long period of time produce desirable effects on PUFAs homeostasis as previously proposed [3, 23].…”

Addition of Palm Oil in Diet of Dairy Ewes Reduces Saturates Fatty Acid and Increases Unsaturated Fatty Acids in Milk

“…PUFA are associated reduction in systemic inflammation [23], protection against atherosclerosis [19], prevention of peripheral artery disease [14], and reduction of steatohepatitis [29]. Alpha linolenic acid (C18:3 -3), popularly known as omega 3, is associated with prevention and treatment of cardiovascular diseases [16], as well as the reduction of inflammation and oxidative stress caused by diabetes mellitus [13]. Thus, the reduction of PUFA levels in milk may have deleterious effects on human consumers.…”

Associations between alcohol intake and diabetic retinopathy risk: a systematic review and meta-analysis

“…Globally, diabetes mellitus (DM) has been rapidly increasing and is estimated to have affected about 422 million people and caused 1.6 million deaths in 2014 [1]. Diabetic patients experience progressive changes in their metabolic and inflammatory indices and several inflammatory markers [2][3][4]. Microvascular abnormalities and eye-related complications are most common in DM patients [5,6].…”