BIOACTIVE COMPONENTS FROM BLACKBERRIES TO AUGMENT DIETARY APPROACHES TO OBESITY TREATMENT OR PREVENTION: INDIRECT CALORIMETRY STUDIES IN MAN AND TISSUE

Abstract

Rodent models of diet-induced obesity lead to the discovery of an anti-obesity and anti-diabetic effect of anthocyanins in several forms. In addition to improved body composition and insulin sensitivity, molecular research suggests the activation of PPAR pathways and corrected or improved mitochondrial function by way of AMPK activation. As the obesity epidemic in the United States progresses, cost effective and practical solutions are warranted, with an emphasis on improved dietary choices. Berries are a readily available source of anthocyanins and promising results on obesity demonstrated in rodents needs to be explored in humans. A randomized, placebo-controlled, cross-over human feeding study was conducted at the Beltsville Human Nutrition Research Center. Twenty-four overweight or obese male subjects followed a 100% investigator controlled high fat diet for seven days that included 600 g of raw blackberries or an energy matched, anthocyanin free control daily. In order to assess changes in the respiratory quotient, energy expenditure, and calculated substrate oxidation, the subjects completed a 24 hour stay in a room-size indirect calorimeter at the end of each diet period. To assess changes in insulin sensitivity, the subjects also participated in a 4-hour meal-based glucose tolerance test on the morning of day seven. Significant findings include a reduction in the respiratory quotient and subsequent increases in the calculated amount of fat oxidized for energy across the 24 hour stay, as well as when calculated during shorter time intervals. Further, insulin sensitivity was increased as evidenced by a reduction in the area under the curve in response to the meal challenge as well as fasting concentrations. Future work should address dosing in longer studies. Supporting cell culture work was conducted in order to determine changes in oxygen consumption at the cellular level. Adipocytes were treated with physiologically attainable levels of cyanidin-3-glucoside and mitochondrial respiration states were characterized with high-resolution respirometry on a fatty acid substrate. Findings include a significant increase in baseline (intact) cellular respiration as well as a marginal increase in the maximum respiratory capacity of the adipocytes, without significant changes in mitochondrial density, suggesting improved function of the adipocyte with fatty acid substrates.