Project Number: 5306-51530-016-03
Project Type: Trust

Start Date: Oct 01, 2007
End Date: Sep 30, 2009

Objective:
The marked rise in the incidence of overweight and obesity in the U.S. has been associated with increasing prevalence of cardiovascular and metabolic diseases, and obesity has been correlated with poor nutriture including low dairy consumption. Excess adiposity often coincides with co-morbidities like dyslipidemia, reduced insulin sensitivity, increased blood pressure and cardiovascular disease, and chronic inflammation in white adipose tissue (WAT) and at other sites. Increased dietary Ca intake in genetically-modified obese animals has been reported to reduce body fat and diminish inflammation and reactive oxygen species (ROS) in WAT. A role for the Ca-regulating factor calcitriol (increased when Ca intake is low) in driving oxidative stress and pro-inflammatory molecule release has been proposed. We hypothesize that increases in Ca intake in diet-induced obese (DIO) mice will thus limit tissue oxidative stress, improve inflammatory profiles in WAT and body-wide, normalize blood lipid profiles, and improve blood sugar regulation. Based on data from the literature, we propose that these beneficial effects will be augmented when Ca is provided within a dairy matrix, and will manifest through mechanisms involving changes in the operation of fat cell mitochondria (the energy-producing component of cells). Our overall objective is to test these concepts in proof-of-principle studies using animal models, with the ultimate goal of translating our findings to clinical and population settings.

Approach:
In Objective 1, we will comprehensively assess metabolic and inflammatory outcomes in DIO mice fed low vs. high levels of Ca, with the aim to test whether inclusion of dietary Ca during the fattening period reduces body fat accumulation and attenuates obesity-related inflammation typically observed in this model (¿prevention model¿). We will determine treatment-related changes in: (1) immune system gene expression and inflammation-related molecule changes in WAT, blood, and other tissues, (2) insulin action and blood sugar control, (3) oxidation state and molecular characterization of blood lipids, (4) vitamin D profile, and (5) body composition (adiposity) and liver fat accumulation. We will also test whether Ca-related changes are more pronounced in mice fed high Ca in food containing nonfat dried milk. In Objective 2, the hypothesis that dietary Ca can reduce obesity-related inflammation and metabolic sequelae when introduced in the context of existing obesity. Again, the idea that Ca is more effective in this regard when delivered in a milk matrix will be evaluated. Documents Trust with Dairy Management, Inc. Log 33532.