CLA-supplemented diet accelerates experimental colorectal cancer by inducing TGF-ß-producing macrophages and T cells.

Conjugated linoleic acid (CLA) has been shown to activate the nuclear receptor PPAR-γ and modulate metabolic and immune functions. Despite the worldwide use of CLA dietary supplementation, strong scientific evidence for its proposed beneficial actions are missing. We found that CLA-supplemented diet reduced mucosal damage and inflammatory infiltrate in the dextran sodium sulfate (DSS)-induced colitis model. Conditional deletion of PPAR-γ in macrophages from mice supplemented with CLA diet resulted in loss of this protective effect of CLA, suggesting a PPAR-γ-dependent mechanism mediated by macrophages. However, CLA supplementation significantly worsened colorectal tumor formation induced by azoxymethane and DSS by inducing macrophage and T-cell-producing TGF-ß via PPAR-γ activation. Accordingly, either macrophage-specific deletion of PPAR-γ or in vivo neutralization of latency-associated peptide (LAP, a membrane-bound TGF-ß)-expressing cells abrogated the protumorigenic effect of CLA. Thus, the anti-inflammatory properties of CLA are associated with prevention of colitis but also with development of colorectal cancer.

Combined swimming and soybean intake reduce early atherosclerotic lesions and serum oxidative stress in mice.

AIM: Physical exercise and soybean intake reduced oxidative stress and atherosclerosis. However, the associated effects of both interventions have not been yet investigated. Thus, we aimed to evaluate the combined effects of swimming and soybean intake on lipid profile, oxidative stress and atherogenesis. METHODS: Ten-week-old male Low-Density Lipoprotein Receptor Knockout mice were divided into 4 groups (N.=8 for each group): control diet without swimming; control diet with swimming; soybean rich diet without swimming and soybean rich diet with swimming. Diets were based on American Institute of Nutrition 93 Growth. The diet of soybean groups was made by soybean extract contained isoflavones. The animals in the exercise groups underwent a 6-week swimming program five times per week. Plasma lipid profile was determined using enzymatic kits. Oxidative stress was measured by thiobarbituric acid reactive substances, hydroperoxide and the lipid oxidation resistance determinations. Atherosclerotic lesions were calculated by morphometry. RESULTS: Soybean intake increased high density lipoprotein cholesterol. Moreover, soybean and exercise individually reduced hepatic oxidative stress and atherogenesis in aortic valve. No additional effect was seen in soybean+exercise group. However, the association of soybean and exercise reduced the percentage of lesion area in arch, thoracic and abdominal aorta and increased serum antioxidant potential. CONCLUSION: Soybean intake and swimming are beneficial in reducing atherosclerosis besides improving lipid profile and reducing lipid peroxidation. The association of soybean and swimming aggregates beneficial effects in serum antioxidant potential and in aorta lesion.

Reciprocal interference of experimental dyslipidemia and food allergy in the evolution of both diseases.

Background. Food allergies have been shown to reduce serum triacylglycerol, glucose, cholesterol, and free fatty acid levels in mice. In turn, dyslipidemias, especially dyslipidemias presenting with low levels of HDL cholesterol, are important risk factors for the development of atherosclerosis. However, the consequences of food allergies on dyslipidemia and atherosclerosis have not been fully investigated. Methods. Food allergy was induced using an egg white solution (EWS) in ovalbumin- (OVA-) sensitized C57BL/6 and low-density lipoprotein receptor knockout mice (LDLr(-/-)) for 5 weeks and was confirmed by the high production of anti-OVA IgE and IgG1 antibodies in both mouse strains. Results. The allergic C57BL/6 mice exhibited EWS aversion that was associated with less visceral fat and high levels of anti-Ova IgE antibodies after 5 weeks of EWS intake compared to controls. However, LDLr(-/-) allergic mice showed reduced anti-Ova IgE levels that were similar to the nonsensitized group. The LDLr(-/-) allergic mice also demonstrated a reversal of food aversion and sustained visceral fat after 5 weeks of allergy. Although HDL cholesterol levels were reduced in both sensitized mouse strains, lipid deposition in thoracic and abdominal aorta as well as area and composition of atherosclerotic plaques as unaffected by chronic ingestion of EWS. Conclusion. LDLr(-/-) mice develop an attenuated food allergy, as they showed a reversal of food aversion and lower IgE production after 5 weeks of induced allergy. The development of atherosclerosis, in turn, was not accelerated in the allergic LDLr(-/-) group despite the more atherogenic lipid profile.