Diets rich in
monounsaturated fatty acids (MUFA) are recommended for individuals with
type 2 diabetes mellitus (T2DM). The American Heart Association recommends increasing intakes of n-3
polyunsaturated fatty acids (PUFA) to reduce the risk of
vascular disease in high-risk individuals; however, the long-term effects of these bioactive
fatty acids on
glucose metabolism in
insulin resistance are controversial. The present studies were conducted to evaluate the effects of diets rich in both MUFA and
alpha linolenic acid (C18:3n-3, ALA),
eicosapentaenoic acid (C20:5n-3, EPA), or
docosahexaenoic acid (C22:6n-3, DHA), on
glycemic control and other parameters related to vascular health in a mouse model of T2DM and
insulin resistance. Male ob/ob mice (n = 15 per treatment) were fed 1 of 4
lipid-modified formula diets (LFDs) for 4 weeks: (1) MUFA control, (2) ALA blend, (3) EPA blend, and (4) DHA blend. A portion of a MUFA-rich
lipid blend in the control LFD was replaced with 11% to 14% energy as
n-3 PUFA. After 4 weeks, plasma
glucose response to a standard meal (1.5 g
carbohydrate/kg
body weight) and
insulin challenge (2 U/kg
body weight, IP) was assessed, and samples were collected for analysis of
glucose,
insulin, and
lipids. Vascular reactivity of isolated aortic rings was assessed in an identical follow-up study. The results showed that
insulin-resistant mice fed an LFD with EPA and/or DHA blends had significantly (P < .05) lower
triglycerides and
free fatty acids, but
insulin sensitivity and fasting plasma
glucose were not improved. However, mice fed with the ALA blend had significantly improved
insulin sensitivity when compared to those fed with other LFD (P < .05). Animals fed an LFD with
n-3 PUFA from marine or plant sources showed significantly improved vascular responses as compared with the MUFA-rich LFD (E(max), P < .05) and ob/ob reference mice consuming chow (E(max) and pEC(50), P < .05). In summary, long-term consumption of LFD with n-3 PUFAs improved blood
lipids and vascular function in an animal model of
insulin resistance and T2DM; however, only MUFA-rich LFD with ALA also improved both
insulin sensitivity and glycemic responses. Further studies of MUFA-rich LFD with ALA with individuals who have T2DM are warranted.