Diet and Systemic Inflammation (DASI)

• Fasting plasma C-reactive protein [ Time Frame: Beginning (day 1) and end (day 9) of each diet period. ] [ Designated as safety issue: No ]
  The concentration of C-reactive protein in fasting plasma will be measured by high-sensitivity assay at the beginning (day 1) and end (day 9) of each 8-day dietary period.
  
  
• Fasting plasma interleukin-6 [ Time Frame: Beginning (day 1) and end (day 9) of each diet period. ] [ Designated as safety issue: No ]
  The concentration of interleukin-6 in fasting plasma will be measured by high-sensitivity enzyme-linked immunosorbent assay at the beginning (day 1) and end (day 9) of each 8-day dietary period.
  
  

• Fasting plasma total and high-molecular weight adiponectin [ Time Frame: Beginning (day 1) and end (day 9) of each diet period. ] [ Designated as safety issue: No ]
  The concentration of total and high-molecular weight adiponectin in fasting plasma will be measured by enzyme-linked immunosorbent assay at the beginning (day 1) and end (day 9) of each 8-day dietary period.
  
  
• Mean daily calorie intake [ Time Frame: The mean daily calorie intake during each of the 8-day diet periods will be calculated. ] [ Designated as safety issue: No ]
  Mean daily calorie intake will be assessed during each of the three 8-day diet periods. All foods will be provided to the subjects in excess of what they are estimated to require, and calorie intake will be assessed by subtracting returned foods from foods administered.
  
  
• Intestinal permeability, as assessed by the 5-hour urinary lactulose/mannitol test [ Time Frame: At the end (day 9) of each diet period. ] [ Designated as safety issue: No ]
  Intestinal permeability will be assessed on day 9 of each diet period by administering a beverage containing 2 g of mannitol and 5 g of lactulose followed by collecting urine for 5 hours afterwards. Recovery of mannitol and lactulose in urine will be measured by gas chromatography, and will be indicative of the degree of intestinal permeability.
  
  
• Fasting plasma zonulin concentrations [ Time Frame: At the end (day 9) of each diet period. ] [ Designated as safety issue: No ]
  Zonulin concentrations will be measured by enzyme-linked immunosorbent assay in fasting plasma collected on day 9 of each diet period. Plasma zonulin is a marker of intestinal permeability.
  
  
• Fasting plasma lipopolysaccharide-binding protein (LBP) [ Time Frame: At the end (day 9) of each diet period. ] [ Designated as safety issue: No ]
  Lipopolysaccharide-binding protein (LBP) will be measured by enzyme-linked immunosorbent assay in fasting plasma collected on day 9 of each diet period. LBP is an acute phase protein secreted by the liver in response to endotoxin (lipopolysaccharide) exposure.
  
  
• Adipose tissue inflammation [ Time Frame: At the end (day 9) of each diet period. ] [ Designated as safety issue: No ]
  A subgroup of the study population will be enrolled into an ancillary study that will aim to assess the effects of consuming fructose- vs. high-fructose corn syrup- vs. glucose-sweetened beverages on adipose tissue inflammation. Adipose tissue inflammation will be assessed by (a) flow cytometric characterization of adipose tissue leukocytes, and (b) whole adipose tissue gene expression analysis. Abdominal subcutaneous adipose tissue samples will be obtained from subjects enrolled into the ancillary study by needle aspiration biopsy on day 9 of each 8-day dietary period.
  
  

The objective of this proposal is to investigate whether fructose-sweetened beverages trigger low-grade systemic inflammation in healthy men and women. Low-grade systemic inflammation, specifically elevated plasma concentrations of C-reactive protein (CRP), is a risk factor for cardiovascular disease (CVD). While it is known that obesity is associated with inflammation, the causes of low-grade inflammation in humans are not well understood. In a pilot study, the consumption of large amounts of fructose-, but not glucose- or aspartame-sweetened beverages potently induced low-grade inflammation in healthy, lean, young men and women in as little as 8 days. The investigators propose to extend these findings by (a) enrolling a greater number of subjects, (b) enrolling obese as well as non-obese subjects, and (c) including a beverage that is sweetened with high fructose corn syrup (HFCS). HFCS is one of the primary sugars consumed in the United States, and a major source of dietary fructose. Our primary specific aim is to assess whether the consumption of fructose- or HFCS-sweetened beverages promotes systemic low-grade inflammation, as measured by plasma concentrations of CRP and IL-6. The investigators hypothesize that plasma CRP and IL-6 concentrations will be elevated after consumption of fructose-containing beverages (fructose and HFCS) when compared to a glucose-sweetened beverage. Our secondary specific aim is to assess whether the consumption of fructose- or HFCS-sweetened beverages lowers plasma adiponectin concentrations. Specifically, the investigators hypothesize that total and high molecular weight (HMW)-adiponectin concentrations in fasting plasma will be lower after subjects have consumed the fructose- or HFCS-sweetened beverages, compared to a glucose-sweetened beverage.

The investigators will recruit 12 obese (BMI between 30 and 40 kg/m2) and 12 non-obese (BMI between 20 and 25 kg/m2) men and women who are free of chronic inflammatory or metabolic disease. In a double-blind, randomized cross-over design, each subject will complete three 8-day standardized dietary periods that will differ only in the type of sweetened beverage administered. Specifically, subjects will be asked to drink four servings of a beverage each day that is sweetened with glucose, fructose, or HFCS (55% fructose, 45% glucose). All solid food will be provided for each of the three 8-day diet periods, and will be consumed ad libitum. Following each dietary period, the investigators will collect fasting blood to measure markers of systemic inflammation and plasma concentrations of total and HMW-adiponectin. We will also assess changes in adipose tissue inflammation and intestinal permeability as potential mechanisms by which fructose-sweetened beverages may trigger systemic inflammation. This study has the potential to identify a dietary trigger of low-grade inflammation, a likely contributor to CVD and metabolic diseases. The public health impact of this project might be considerable given that the consumption of fructose in the population is pervasive, and is modifiable on an individual as well as a population level.