CRP is produced by the liver in response to factors released from macrophages and adipocytes. High circulating CRP concentrations are therefore an indicator of inflammation and/or injury. We examined the effects of dietary fructose on plasma CRP concentrations in a nonhuman primate model of diet-induced metabolic syndrome. Adult male rhesus macaques 12±3 years of age, weighing 16.2±1.9 kg (n=29) maintained on chow (LabDiet 5047) ad libitum were provided with flavored fructose beverages containing 75g of fructose (300 kcal/day). Fasting plasma samples were collected at baseline and after 1 and 3 months. Indices of glucose homeostasis (insulin, glucose, HOMA-IR), adiposity/metabolic homeostasis (leptin, adiponectin) and lipid metabolism (TG, cholesterol, LDL-C, HDL-C, VLDL-C, ApoA1, ApoB, ApoC3 and ApoE) were analyzed. Fructose consumption induced weight gain +1.5±0.2 kg, and insulin resistance, accompanied by increases of plasma leptin, decreased adiponectin, hypertriglyceridemia and increases of ApoC3 and ApoE. Plasma CRP increased from 1.9±0.2 mg/l to 2.9±0.3 mg/l (%∆ = 81±13%) and 2.9±0.3 mg/l (%∆ = +91±14%; both p<0.001) at 1 and 3 months respectively. Bivariate correlation analysis of log-transformed data compared fructose-induced changes (Δ) of CRP with Δ’s of body weight and metabolic indices. After 1 month of fructose consumption, strong positive associations were identified between ΔCRP and ΔApoE (r=0.62, p<0.001), ΔApoC3 (r=0.56, p=0.002), and negatively with Δadiponectin (r=-0.49, p=0.007). After 3 months of fructose exposure, the strong associations between ΔCRP and ΔApoE (r=0.49, p=0.007) and significant relationships with ΔApoC3 (r=0.45, p=0.015) and Δadiponectin (r=-0.39, p=0.038) remained. These results support an important link between fructose diet-induced inflammation with changes of the anti-inflammatory adipocyte hormone (adiponectin) and dysregulated hepatic lipoprotein metabolism.
P.J. Havel: Research Support; Self; Arrowhead Research, Bristol-Myers Squibb Company, Magnamosis Inc. J.L. Graham: Research Support; Self; Arrowhead Research, Bristol-Myers Squibb Company, Magnamosis Inc. K.L. Stanhope: None. A. Butler: None.
National Institutes of Health