ABSTRACT
PURPOSE: The effect of polyphenol-rich cloudy apple juice (CloA) consumption on plasma parameters related to the obesity phenotype and potential effects of interactions between CloA and allelic variants in obesity candidate genes were assessed in obese men. METHODS: In this controlled, randomized, and parallel study, n = 68, non-smoking, non-diabetic men with a BMI ≥27 kg/m(2) received 750 mL/day CloA (802.5 mg polyphenols) or 750 mL/day control beverage (CB, isocaloric equivalent to CloA) for 4 weeks. Further, study participants were genotyped for single-nucleotide polymorphisms in PPARγ (rs1801282), UCP3 (rs1800849), IL-6 (rs1800795), FABP2 (rs1799883), INSIG2 (rs7566605), and PGC1 (rs8192678) genes. At the beginning and at the end of intervention plasma lipids, distinct adipokines and cytokines as well as anthropometric parameters were determined. RESULTS: CloA compared to CB had no significant effect on plasma lipids, plasma adipokine and cytokine levels, BMI, and waist circumference. However, CloA consumption significantly reduced percent body fat compared to CB (∆ % body fat: CloA: -1.0 ± 1.3 vs. CB: -0.2 ± 0.9, p < 0.05). The IL-6-174 G/C polymorphism showed an interaction with body fat reduction induced by CloA. Solely in C/C, but not in G/C or G/G variants, a significant reduction in body fat after 4 weeks of CloA intervention was detectable. CONCLUSION: The observed diet-gene interaction might be a first indication for the impact of individual genetic background on CloA-mediated bioactivity on obesity-associated comorbidities.
Subject(s)
Beverages , Body Composition , Diet , Genetic Markers , Malus/chemistry , Obesity/genetics , Adipokines/blood , Adipose Tissue/metabolism , Adult , Aged , Alleles , Body Mass Index , Fatty Acid-Binding Proteins/genetics , Fatty Acid-Binding Proteins/metabolism , Gene-Environment Interaction , Genotype , Humans , Interleukin-6/blood , Interleukin-6/genetics , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Ion Channels/genetics , Ion Channels/metabolism , Lipids/blood , Male , Membrane Proteins/genetics , Membrane Proteins/metabolism , Middle Aged , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Obesity/physiopathology , PPAR gamma/genetics , PPAR gamma/metabolism , Polymorphism, Single Nucleotide , Sequence Analysis, DNA , Uncoupling Protein 3 , Waist Circumference , Young AdultABSTRACT
It is estimated that 75-85% of all chronic diseases are linked to lifestyle-related and environmental factors. The development of colon cancer is positively associated with obesity and inversely associated with the intake of dietary fibre, fruit and vegetable. Apple juice is the most widely consumed fruit beverage in Germany. It contains a specific spectrum of polyphenols and other components that may reduce the risk of colon cancer. Epidemiologic studies suggest an inverse correlation between apple consumption and colon cancer risk, although the mechanisms for these observations are not clear. The present review summarizes the preventive potential of apple juices and different apple constituents on biomarkers related to colon carcinogenesis with special focus on the in vivo evidence and the cancer promoting condition of obesity. However, under the cancer promoting condition of obesity, apple juice did not show cancer-preventive bioactivity. In our experiments a cancer-preventive bioactivity of apple juice is lacking in rats under the cancer-promoting condition of obesity. To further investigate, whether this lack of efficacy observed in obese rats might be representative for obese individuals human intervention studies on high risk groups such as obese or diabetic individuals are of interest and will be conducted.
Subject(s)
Anticarcinogenic Agents/administration & dosage , Beverages , Colonic Neoplasms/prevention & control , Diet , Malus/chemistry , Obesity/physiopathology , Animals , Beverages/analysis , Fruit/chemistry , HumansABSTRACT
BACKGROUND: Obesity and energy restriction modulate the development of precancerous aberrant crypt foci (ACF) in animal models of colon cancer. AIM: Investigation of the major obesity-associated determinants for ACF-development and underlying mechanisms leading to ACF-modulation, such as changes in DNA damage or colonocytes hyperproliferation. METHODS: Lean and obese Zucker rats fed ad libitum (a.l.) or obese pair fed (p.f.) were induced with 1,2-dimethylhydrazine (DMH) for colon cancer. Multiple regression analyses were performed to identify major metabolic factors correlated with ACF number and size (aberrant crypts/ACF). DNA damage is analyzed by the comet-assay, epithelial proliferation by immunohistochemistry. RESULTS: Aberrant crypt foci number was significantly elevated in Zucker obese a.l. (205.7+/-65.4 vs. lean 9.5+/-6.3, P<0.05) and is reduced by pair feeding in Zucker obese rats (81.4+/-28.5 vs. obese a.l., P<0.05). Compared to lean the ACF size was higher in Zucker obese a.l. (2.1+/-0.3 vs. lean 1.3+/-0.2., P<0.05) but is not reduced by pair feeding (1.7+/-0.2; P>0.05). While ACF number and size were modulated by genotype and/or pair feeding the DMH-induced DNA damage and hyperproliferation in colonocytes did not differ significantly between groups. Regression analysis showed that plasma parameters associated with lipid-metabolism (triglycerides, cholesterol, malondialdehyde) significantly correlated with the ACF number and size while parameters linked to carbohydrate-metabolism (glucose, insulin) were weaker determinants. CONCLUSION: Obesity or pair feeding-associated modulation of ACF correlate with parameters related to lipid-metabolism but is not accompanied by changes in DNA damage and proliferation.
