Aldo R. Eynard

Overweight and obesity: a review of their relationship to metabolic syndrome, cardiovascular disease, and cancer in South America

Socioeconomic and demographic transformations are occurring very rapidly in some areas of the world, especially in South America, and are accompanied by changes in lifestyle, dietary patterns, and the epidemiological profile of prevalent diseases. This review examines whether obesity and overweight are related to metabolic syndrome, cardiovascular disease, and cancer in South America. Research carried out in more than 6,000 cases and controls was evaluated, along with most of the available publications related to South America. In South America, obesity and risk factors for cardiovascular disease are related mainly to aging, ethnicity effects, and preventable risky lifestyle conditions. Most of the studies that found an association between cancer and obesity are from the Southern Cone, the geographic area most affected by this pathology. Overall, the prevalence of metabolic syndrome was highest in Chile, followed in decreasing order by Colombia, Peru, Argentina, and Ecuador, with differences noted between urban and rural areas or between urban and periurban areas. Obesity and cancer may be preventable, at least in part, by healthy behavior; hence, exercise, weight control, and healthy dietary habits are important to reduce the risk of these major chronic diseases.

Beneficial action of resveratrol: How and why?

Flavonoid resveratrol modulates the transcription factor NF-κB; inhibits the cytochrome P450 isoenzyme CYP1 A1; suppresses the expression and activity of cyclooxygenase enzymes; and modulates Fas/Fas-ligand-mediated apoptosis, p53, mammalian target of rapamycin, and cyclins and various phosphodiesterases. This increases the cytosolic cAMP that activates Epac1/CaMKKβ/AMPK/SIRT1/PGC-1α pathway, which in turn facilitates increased oxidation of fatty acids, mitochondrial biogenesis, mitochondrial respiration, and gluconeogenesis. Resveratrol triggers apoptosis of activated T cells and suppresses tumor necrosis factor-α, interluekin-17 (IL-17), and other proinflammatory molecules, and thus is of benefit in autoimmune diseases. In addition, resveratrol inhibits expression of hypoxia-inducible factor-1α and vascular endothelial growth factor, explaining its effective action against cancer. Brain-derived neurotrophic factor (BDNF) that is involved in the pathogenesis of obesity, type 2 diabetes mellitus, and metabolic syndrome is also altered in depression, schizophrenia, bipolar disorder, and autism. We noted that BDNF protects against cytotoxic actions of alloxan, streptozotocin, and benzo(a)pyrene. Resveratrol prevents bisphenol A-induced autism, type 2 diabetes mellitus, and metabolic syndrome, suggesting that it may augment BDNF synthesis and action. We also observed that BDNF levels are low in type 2 diabetes mellitus and that BDNF enhances production of antiinflammatory lipid, lipoxin A4, whose levels are low in diabetes mellitus. Thus, resveratrol may augment production of lipoxin A4. Resveratrol alters gut microbiota and influences stem cell proliferation and differentiation. These pleiotropic actions of resveratrol may explain the multitude of its actions and benefits.

Alcohol, methylxanthine-containing beverages, and colorectal cancer in Córdoba, Argentina.

The relationship between social class indicators, body mass index (BMI), selected life-style habits (alcohol, coffee, maté and tea drinking) and colorectal cancer was investigated in a case-control study conducted between 1993 and 1997 in Córdoba, Argentina, a relatively high mortality area for colorectal cancer. Cases were 190 patients below age 80 years with incident, histologically confirmed colorectal adenocarcinomas, and controls were 393 patients admitted to hospital for a wide spectrum of acute, non-neoplastic disorders. Higher social class, based on occupation of the head of the household, was significantly associated with colorectal cancer risk: the odds ratios (OR) and 95% confidence intervals (95% CI) were 1.9 (1.2-2.9) for intermediate and 2.0 (1.2-3.4) for the highest as compared to the lowest social class individuals. When compared with subjects whose BMI was<25 kg/m2, the OR was 1.1 (0.7-1.6) for those with BMI 25 to 29 kg/m2, and 1.3 (0.7-2.3) for those ≥ 30. In comparison with alcohol abstainers, the OR was 2.8 (1.6-5.1) for drinkers, and there was a significant trend in risk with dose. The association was observed with wine (the most common alcoholic beverage in Argentina), as well as for beer and spirits. The consumption of coffee, mate and tea was not significantly related to colorectal cancer, but the ORs were below unity (0.9 (0.7-1.3) for coffee, 0.9 (0.6-1.5) for mate and 0.8 (0.6-1.2) for tea drinkers). The relationship between social class, alcohol drinking and colorectal cancer were consistent across strata of sex and age. This study confirms that colorectal cancer has positive social class correlates. The association with alcohol drinking is apparently stronger than previously reported, and may be due to the role of chance and/or peculiar correlates of alcohol drinking in this Argentinean population

Effect of ω-3 and ω-9 fatty acid rich oils on lipoxygenases and cyclooxygenases enzymes and on the growth of a mammary adenocarcinoma model

BackgroundNutritional factors play a major role in cancer initiation and development. Dietary polyunsaturated fatty acids (PUFAs) have the ability to induce modifications in the activity of lipoxygenase (LOX) and cyclooxygenase (COX) enzymes that affect tumour growth. We studied the effect of two diets enriched in 6% Walnut and Peanut oils that are rich in ω-3 and ω9 PUFAs respectively on a murine mammary gland adenocarcinoma as compared with the control (C) that received commercial diet.ResultsPeanut oil enriched diet induced an increase in membrane arachidonic acid (AA) content and the cyclooxygenase enzyme derived 12-HHT (p < 0.05) and simultaneously showed decrease in 12-LOX, 15-LOX-2, 15-LOX-1 and PGE activities (p < 0.05) that corresponded to higher apoptosis and lower mitosis seen in this group (p < 0.05). Furthermore, Peanut oil group showed lower T-cell infiltration (p < 0.05), number of metastasis (p < 0.05) and tumour volume (p < 0.05) and longer survival rate compared to other groups.ConclusionsThe results of the present study showed that Peanut oil-enriched diet protects against mammary cancer development by modulating tumour membrane fatty acids composition and LOX and COX enzyme activities.

Artificial sweetener consumption and urinary tract tumors in Cordoba, Argentina

OBJECTIVE To determine the role of the habitual use of the most common artificial sweeteners (AS) in the development of urinary tract tumors (UTT) in Argentina. METHODS Case-control study of 197 patients with histologically confirmed UTT of transitional varieties, and 397 controls with acute, non-neoplastic, and non-urinary tract diseases, admitted to the same hospitals in Córdoba (Argentina) between 1999 and 2006. All subjects were interviewed about their use of AS and their exposure to other known or suspected risk factors for UTT. RESULTS Fifty-one UTT patients (26%) and 87 controls (22%) used AS. The risk of UTT was significantly increased in long-term (> or =10 years) AS users compared with none-AS users. The OR (95% CI) for long-term consumers was 2.18 (1.22-3.89) and for short-term users was 1.10 (0.61-2.00) after adjustment for age, gender, BMI, social status. and years of tobacco use. CONCLUSION Regular use of AS for 10 years or more was positively associated with UTT.

Cancer incidence pattern in Cordoba, Argentina.

Cancer is the second cause of death in Argentina; nevertheless the distribution of the cancer incidence rates throughout the country is unknown. This study was conducted to describe cancer incidence patterns in Córdoba Province. Incidence data were supplied by the Government Córdoba Cancer Registry. Demographic information (age, sex, and place of residence) and diagnosis, certified by a pathologist, about all incident cases from June 2003 to May 2005 by type and 5-year age groups were obtained. Comparison of the incidence rate of cancer in various counties was performed by using standardized incidence rates (SIR) per 100 000 inhabitants using the world standard population. Estimated SIRs were used to build up incidence maps. Two indicators were created: sex ratio and site-specific ratio. Mixed Poisson models were fitted. Taken as a whole for all counties, SIR was 121.42 and 141.57 for men and women, respectively. The most common sites in men were prostate (13.62), lung (10.12), colon (7.53), and bladder (7.03); in women were breast (22.51) and colon (3.31). The highest and lowest rates were in urban and rural areas, respectively. Cancer registry has a pivotal role in cancer control. Such information is the primary resource of information not only for epidemiological research on cancer determinants but also for planning and evaluating health services for the policies of prevention, diagnosis and treatment of the disease.

Conjugated linoleic acid (CLA) versus saturated fats/cholesterol: their proportion in fatty and lean meats may affect the risk of developing colon cancer

In spite of the considerable amount of experimental, clinical and epidemiological research about the consumption of red meat, total fats, saturated/unsaturated fatty acids and cholesterol with regard to the risk of developing colorectal cancer (CRC), the issue remains controversial. The general belief is a reduction of red meat intake, and subsequent nutritional advice usually strongly recommends this. Paradoxically, beef together with whole milk and dairy derivatives, are almost the only sources for conjugated linoleic acid (CLAs) family. Furthermore CLAs are the only natural fatty acids accepted by the National Academy of Sciences of USA as exhibiting consistent antitumor properties at levels as low as 0.25 – 1.0 per cent of total fats. Beside CLA, other polyunsaturated fatty acids (PUFA) belonging to the essential fatty acid (EFA) n-3 family, whose main source are fish and seafood, are generally believed to be antipromoters for several cancers. The purpose of this work is to critically analyze the epidemiological and experimental evidence by tentatively assuming that the reciprocal proportions of saturated fats (SA) plus cholesterol (CH) versus CLAs levels in fatty or lean beef may play an antagonistic role underlying the contradictory effects reported for red meats consumption and CRC risk. Recent results about meat intake and risk for CRC in Argentina have shown an unexpected dual behaviour related to the type of meats. Fatty meat derivatives, such as cold cuts and sausages, mainly prepared from fatty beef (up to 37% fat) were associated with higher risk, whereas high consumption of lean beef (< 15% fat) behaved as a protective dietary habit. CLA is located in the interstitial, non-visible, fat evenly distributed along muscle fibres as well as in subcutaneous depots. Visible fat may be easily discarded during the meal, whereas interstitial fats will be eaten. The remaining intramuscular fat in lean meats range from 25 to 50 g/Kg (2.5 to 5%). The proportion of CLA/SA+CH for lean beef eaters is 0.09 and the fatty mets 0.007 (g/100 g). As a consequence, the beneficial effects of minor amounts of CLA may be relatively enhanced in lean meat compared to fatty meat sub-products which contain a substantial amount of saturated fatty acids and cholesterol, as in cold cuts and cow viscera.

Basic aspects of tumor cell fatty acid-regulated signaling and transcription factors

This article reviews the current knowledge and experimental research about the mechanisms by which fatty acids and their derivatives control specific gene expression involved during carcinogenesis. Changes in dietary fatty acids, specifically the polyunsaturated fatty acids of the ω-3 and ω-6 families and some derived eicosanoids from lipoxygenases, cyclooxygenases, and cytochrome P-450, seem to control the activity of transcription factor families involved in cancer cell proliferation or cell death. Their regulation may be carried out either through direct binding to DNA as peroxisome proliferator-activated receptors or via modulation in an indirect manner of signaling pathway molecules (e.g., protein kinase C) and other transcription factors (nuclear factor kappa B and sterol regulatory element binding protein). Knowledge of the mechanisms by which fatty acids control specific gene expression may identify important risk factors for cancer and provide insight into the development of new therapeutic strategies for a better management of whole body lipid metabolism.

Association between E-cadherin expression by human colon, bladder and breast cancer cells and the 13-HODE:15-HETE ratio. A possible role of their metastatic potential ☆

The relationship between 15(S)-HETE and 13(S)-HODE from different human tumor cells exposed to n-6 and n-3 essential fatty acids (EFAs) and E-cadherin expression was studied. Colon cancer cells (HRT-18) exposed to gamma linoleic acid (18:3n-6, GLA) and eicosapentaenoic (20:5n-3, EPA) (50microM) showed an increased expression of E-cadherin. Breast cancer (MCF-7) exposed to EPA showed an increment whereas GLA had no effect on E-cadherin expression. No expression of E-cadherin was observed for urothelial cancer (T-24) after GLA or EPA treatment. Significant levels of 15(S)-HETE and 13(S)-HODE were detected after GLA or EPA treatment for all tumor lines. E-cadherin expression was inversely proportional to the 13(S)-HODE:15(S)-HETE ratio when cells were pretreated with GLA or EPA. Nevertheless, the liberation of these metabolites seems to be independent of the E-cadherin expression. The increase in the13(S)-HODE:15(S)-HETE correlates to a decrease in the expression of E-cadherin. Both factors may play a role in metastasis development.

Quercetin enhances pretumorous lesions in the NMU model of rat pancreatic carcinogenesis

The effect of dietary quercetin (Q) was evaluated in rats treated with nitrosomethylurea (NMU). Pancreatic nodules and focal acinar cell hyperplasias were observed in groups treated with NMU (87%) and Q-NMU (100%). Although rats with dysplastic foci (27%) were found in the NMU-treated group, Q-NMU treatment resulted in a significantly higher number of rats with dysplastic foci (73%). Furthermore, carcinomas in situ (12%) and one microcarcinoma (4%) were found in these animals. Mitosis was significantly increased and apoptosis was diminished in focal acinar cell hyperplasias of the Q-NMU group. Our present results support a promoting and progressing effect of quercetin in the NMU model of rat pancreatic carcinogenesis.