Weight Changes and Metabolic Outcomes in Calorie-Restricted Obese Mice Fed High-Fat Diets Containing Corn or Flaxseed Oil: Physiological Role of Sugar Replacement with Polyphenol-Rich Grape

Objective: Because diet components are important during dieting in obesity treatment, we examined possible beneficial effects of substituting corn oil and sugar with flaxseed oil and grape in calorie-restricted high-fat diets on weight changes as well as improvement in some metabolic markers and related gene expression.Methods: Seventy-five C57BL/6J male mice were given free access to a high-fat (36% of energy from fat) diet containing corn oil plus sugar (CO + S). After 11weeks, 15 mice were sacrificed and another 60 were divided among 4 high-fat diet groups with 30% calorie restriction (CR) for the next 12weeks. The diets contained corn oil (CO) or flaxseed oil (FO) with sugar (S) or grape (G).Results: Despite CR, a weight loss trend was observed only during the first 4weeks in all groups. CR did not significantly increase SIRT1 gene expression. Higher liver weight was observed in mice consuming FO (p < 0.05). Proliferator-activated receptor gamma (PPAR) expression decreased in FO + G-CR significantly and even with a reduction of adiposity and higher adiponectin levels, fasting blood sugar (FBS) was significantly higher than in CO + G-CR. Grape intake increased Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1) expression and decreased insulin resistance in CO + G-CR.Conclusions: Sugar replacement with polyphenol-rich grape along with CR improved glucose homeostasis, and substituting corn oil with flaxseed oil in obese mice reduced fat mass, but even with no change in adiponectin levels it could not decrease insulin resistance. However, none of the food item combinations facilitated weight reduction in the long-term CR. Therefore, regardless of the total calorie intake, different diet components and fat contents may have unexpected effects on metabolic regulation.