Beneficial effects of a plant-fish oil, slow carbohydrate diet on cardio-metabolic health exceed the correcting effects of metformin-pioglitazone in diabetic pigs fed a fast-food diet

PLOS ONE(2021)

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摘要
Background Lifestyle influences endocrine, metabolic and cardiovascular homeostasis. This study investigated the impact of diet and oral anti-diabetic medication on cardio-metabolic health in human-sized diabetic pigs. Methods After a growing pre-phase from similar to 30 to similar to 69 kg during which domestic pigs were fed either a low fat, low sucrose diet (group A) or a fast food-type diet elevated in lard (15%) and sucrose (40%) (group B), the pigs were subdivided in 5 groups (n = 7-8 pigs per group). Group 1, normal pigs from group A on a low fat, low sugar (L) pig diet and group 2, normal pigs from group B on a high lard (25%), sucrose-fructose (40%), cholesterol (1%) fast food-type (F) diet. Diabetes (D) was induced in group B pigs by streptozotocin and group 3 received the F diet (DF), group 4 received the F diet with Anti-diabetic medication metformin (2 g.day(-1) )pioglitazone (40 mg.day(-1)) (DFA) and group 5 switched to a Plant-Fish oil (25%), Slowly digestible starch (40%) diet (DPFS). The F and PFS diets were identical for fat, carbohydrate and protein content but only differed in fat and carbohydrate composition. The 5 pig groups were followed up for 7 weeks until reaching similar to 120 kg. Results In normal pigs, the F diet predisposed to several abnormalities related to metabolic syndrome. Diabetes amplified the inflammatory and cardiometabolic abnormalities of the F but both oral FA medication and the PFS diet partially corrected these abnormalities (mean +/- SEM) as follows: Fasting plasma TNF-alpha (pg.ml(-1)) and NEFA (mmol.l(-1)) concentrations were high (p<0.02) in DF (193 +/- 55 and 0.79 +/- 0.16), intermediate in DFA (136 +/- 40 and 0.57 +/- 012) and low in DPFS pigs (107 +/- 31 and 0.48 +/- 0.19). Meal intolerance (response over fasting) for glucose and triglycerides (area under the curve, mmol.h(-1)) and for lactate (3-h postprandial, mmol.l(-1)) was high (p<0.03) in DF (489 +/- 131, 8.6 +/- 4.8 and 2.2 +/- 0.6), intermediate in DFA (276 +/- 145, 1.4 +/- 1.1 and 1.6 +/- 0.4) and low in DPFS (184 +/- 62, 0.7 +/- 1.8 and 0.1 +/- 0.1). Insulin-mediated glucose disposal (mg.kg(-1).min(-1)) showed a numerical trend (p = NS): low in DF (6.9 +/- 2.2), intermediate in DFA (8.2 +/- 1.3) and high in DPFS pigs (10.4 +/- 2.7). Liver weight (g. kg(-1) body weight) and liver triglyceride concentration (g.kg(-1) liver) were high (p<0.001) in DF (23.8 +/- 2.0 and 69 +/- 14), intermediate in DFA (21.1 +/- 2.0 and 49 +/- 15) and low in DPFS pigs (16.4 +/- 0.7 and 13 +/- 2.0). Aorta fatty streaks were high (p<0.01) in DF (16.4 +/- 5.7%), intermediate in DFA (7.4 +/- 4.5%) and low in DPFS pigs (0.05 +/- 0.02%). Conclusion This translational study using pigs with induced type 2 diabetes provides evidence that a change in nutritional life style from fast food to a plant-fish oil, slowly digestible starch diet can be more effective than sole anti-diabetic medication.
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