Dietary cholecalciferol and calcium levels in a western-style defined rodent diet alter energy metabolism and inflammatory responses in mice

Male and female C57Bl6 mice were fed a control AIN76A diet, a new Western-style diet (NWD1) reflecting dietary patterns linked to elevated colon cancer incidence (higher fat, lower cholecalciferol, calcium, methyl donors, fiber), or NWD1 with elevated cholecalciferol and calcium (NWD2) from weaning. After 24 wk, serum 25-hydroxyvitamin D [25(OH)D] decreased by >80% in the NWD1 group compared with controls, but with no alteration in serum calcium or bone mineral density. The decreased serum 25(OH)D was prevented in the NWD2 group. After 32 wk, the NWD1 group compared with controls reduced overall energy expenditure by 15% without altering food consumption or physical activity and induced glucose intolerance, phenotypes associated with metabolic syndrome. These responses were unexpectedly exacerbated in the NWD2 group, further shifting mice toward greater fatty acid storage rather than oxidation compared with both control and NWD1 groups, but there was no change in physical activity, causing significant weight gain due to increased fat mass. The NWD1 group also exhibited inflammatory responses compared with controls, including macrophageassociated crown-like structures in epididymal adipose tissue and increased serum concentrations of the proinflammatory cytokine IL-1β, and of its targets, MCP-1 and Rantes, which were prevented or greatly mitigated in the NWD2 group. However, there was also elevated lipid storage in the liver and steatosis not seen in the control and NWD1 groups. Thus, elevating cholecalciferol and calcium in aWestern-style diet can reduce inflammation associated with risk for colon tumor development, but interaction of nutrients in this diet can compromise liver function when fed long term.