Fátima Pérez de Heredia

Obesity, inflammation and the immune system.

Obesity shares with most chronic diseases the presence of an inflammatory component, which accounts for the development of metabolic disease and other associated health alterations. This inflammatory state is reflected in increased circulating levels of pro-inflammatory proteins, and it occurs not only in adults but also in adolescents and children. The chronic inflammatory response has its origin in the links existing between the adipose tissue and the immune system. Obesity, like other states of malnutrition, is known to impair the immune function, altering leucocyte counts as well as cell-mediated immune responses. In addition, evidence has arisen that an altered immune function contributes to the pathogenesis of obesity. This review attempts to briefly comment on the various plausible explanations that have been proposed for the phenomenon: (1) the obesity-associated increase in the production of leptin (pro-inflammatory) and the reduction in adiponectin (anti-inflammatory) seem to affect the activation of immune cells; (2) NEFA can induce inflammation through various mechanisms (such as modulation of adipokine production or activation of Toll-like receptors); (3) nutrient excess and adipocyte expansion trigger endoplasmic reticulum stress; and (4) hypoxia occurring in hypertrophied adipose tissue stimulates the expression of inflammatory genes and activates immune cells. Interestingly, data suggest a greater impact of visceral adipose tissue and central obesity, rather than total body fat, on the inflammatory process. In summary, there is a positive feedback loop between local inflammation in adipose tissue and altered immune response in obesity, both contributing to the development of related metabolic complications.

Adiponectin, the controversial hormone

OBJECTIVE To discuss present knowledge about adiponectin hormone. DESIGN Review of existing literature. SETTING AND RESULTS Adiponectin is one of the most interesting cytokines associated with obesity, although its physiological role remains to be fully clarified. Adiponectin is a 247-amino acid protein that contains four differentiable domains. Contrary to most adipose-related cytokines, adiponectin levels are surprisingly lower in obese than in lean humans. Women have been found to have significantly higher adiponectin plasma concentrations than men. Further research is needed in order to identify new polymorphisms which contribute to explain the potential role of adiponectin in obesity and related pathologies. Considering the anti-inflammatory properties of adiponectin and the fact that it is negatively associated with adiposity, this cytokine could be one of the links between obesity and inflammation. The main mechanisms of action of adiponectin are directed to a protective role against atherogenic and insulin resistance processes. Research has revealed interesting new functions far beyond metabolism, such as immunity, cancer and bone formation. Contrary to all adipose-related proteins, adiponectin decreases with obesity. Most of the contradictory data surrounding adiponectin are related to plasma values and their relationship with body fat, gender differences and insulin resistance. There are important confounding results regarding the mechanisms of action and functions of adiponectin, especially in relation to insulin resistance and inflammation.

Functional foods and nutraceuticals as therapeutic tools for the treatment of diet-related diseases

In Western societies, the incidence of diet-related diseases is progressively increasing due to greater availability of hypercaloric food and a sedentary lifestyle. Obesity, diabetes, atherosclerosis, and neurodegeneration are major diet-related pathologies that share a common pathogenic denominator of low-grade inflammation. Functional foods and nutraceuticals may represent a novel therapeutic approach to prevent or attenuate diet-related disease in view of their ability to exert anti-inflammatory responses. In particular, activation of intestinal T regulatory cells and homeostatic regulation of the gut microbiota have the potential to reduce low-grade inflammation in diet-related diseases. In this review, clinical applications of polyphenol-rich functional foods and nutraceuticals in postprandial inflammation, obesity, and ageing will be discussed. We have placed special emphasis on polyphenols since they are broadly distributed in plants.

Age-related changes in fatty acids from different adipose depots in rat and their association with adiposity and insulin

OBJECTIVE We studied age-related changes in fatty acids (FAs) from serum and adipose tissue in rats by comparing different adipose regions and analyzed their relations to adiposity and insulin function. METHODS Female weaned rats were fed on a high-fat diet until 6, 14, and 20 mo of age (n = 12, n = 6, n = 10, respectively). Body weight, adiposity, serum insulin, serum glucose, and homeostatic model assessment index were measured. FA compositions from serum and interscapular brown, periovarian, mesenteric, and subcutaneous tissues were determined by gas chromatography. RESULTS Body weight and adiposity increased with age; visceral depots grew by hypertrophy, whereas subcutaneous depots grew by hyperplasia and in a higher ratio. Initially, the mesenteric tissue showed greater saturated and trans-FA contents, whereas brown tissue had higher polyunsaturated FA (PUFA) proportions. Aging resulted in a lower saturation degree in adipose tissue, attenuating earlier differences among depots. There was an elevation in omega-6 PUFAs with age, mainly because of C18:2omega-6, whereas omega-3 long-chain PUFAs, C20:5omega-3 and C22:6omega-3, tended to decrease in serum and adipose tissue. Adiposity was associated positively with monounsaturated FAs and inversely with PUFAs; insulin-related variables correlated negatively with serum omega-6 PUFA but positively with serum monounsaturated FAs and subcutaneous depot trans-FAs. CONCLUSION The mesenteric tissue showed the least favorable FA profile compared with the other depots, but differences among adipose regions diminished with age. In rats fed a high-fat diet, aging resulted in a lower saturation degree, with increased values in the cardiometabolic risk factor omega-6/omega-3 ratio in serum and adipose tissue.

Self-reported sleep duration, white blood cell counts and cytokine profiles in European adolescents: the HELENA study

BACKGROUND Sleep patterns face important changes during adolescence. This can have implications for the immune system, which is regulated by the sleep-wake cycle; however, most studies relating sleep and immune system have been conducted on adults. OBJECTIVE To study the relationships between sleep duration, immune cell counts, and cytokines in European adolescents participating in the HELENA Cross-Sectional Study. METHODS Adolescents (12.5-17.5 years; n = 933; 53.9% girls) were grouped according to self-reported sleep duration into <8, 8-8.9 and ≥9 h/night. Blood samples were collected in the morning after an overnight fast to analyze counts of white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils, the lymphocyte subsets CD3(+), CD4(+), CD8(+), CD45RA(+), CD45RO(+), CD3(-)CD16(+)56(+) and CD19(+), and concentrations of cortisol, CRP, IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α and IFN-γ. Pro-/anti-inflammatory and Th1/Th2 cytokine ratios were calculated. Immune parameters were correlated to sleep duration and compared between the three groups. RESULTS Sleep duration was negatively associated with cortisol levels and WBC, neutrophil, monocyte, CD4(+) and CD4(+)CD45RO(+) counts; in girls it is also negatively associated with IL-5 and IL-6 levels. The 8-8.9 h/night group presented the highest IL-4 values and the lowest pro-/anti-inflammatory and Th1/Th2 cytokine ratios. CONCLUSION A sleep duration of 8-8.9 h/night was associated with a healthier immune profile in our adolescents.

Effect of dehydroepiandrosterone on protein and fat digestibility, body protein and muscular composition in high-fat-diet-fed old rats

The main objective of the present study was to examine the effects of dehydroepiandrosterone (DHEA) on the digestive efficiency of dietary protein and fat. Second, we analysed the specific changes in muscle composition induced by the hormone. DHEA was given in the diet (0 x 5 %, w/w) to 75-week-old, high-fat-fed Sprague-Dawley rats (n 11) for 13 weeks; age- and weight-matched rats fed on the same diet without DHEA supplementation were used as controls (n 10). To determine dietary protein and fat apparent digestibility coefficients, 1-week 24 h faecal depositions were collected. In parallel, urine N was assessed. These assays were performed twice, in the short term (2-week treatment) and in the long term (13-week treatment). Body and gastrocnemius muscle compositions were also analysed. The present results show that DHEA decreased energy intake, body weight, body fat, adipocyte size and number (P<0 x 001). The feed efficiency ratio indicates that DHEA-treated rats were less efficient in transforming nutrients fed into their own biomass. Also, a short-term reduction in protein digestibility (P<0 x 05) and in body-protein degradation (P<0 x 01) was found in DHEA-treated rats, resulting in an increased content of body protein (P<0 x 05). Gastrocnemius muscles were smaller, as a result of fat (P<0 x 05) but not protein reduction. In conclusion, we confirm the slimming effect of DHEA and, for the first time, we demonstrate that DHEA has an effect at the digestive level. The anti-obesity properties of DHEA could be related to a reduction in protein digestibility in the short term and a protective effect on body protein with a selective mass loss from body fat.

Eating Habits and Total and Abdominal Fat in Spanish Adolescents: Influence of Physical Activity. The AVENA Study

OBJECTIVE To evaluate the association between specific dietary habits and body fatness in Spanish adolescents, and to analyze the role of leisure-time physical activity (LTPA) in this association. METHODS In this cross-sectional study, 1,978 adolescents (1,017 girls) aged 13.0-18.5 years from the AVENA (Alimentación y Valoración del Estado Nutricional en Adolescentes) study were included. Particular dietary habits (breakfast, mid-morning snack, lunch, afternoon snack, dinner, and nighttime snack, as well as time spent eating, number of meals, consumption of soft drinks, and ready-to-eat foods) and LTPA were self-reported and analyzed as dichotomic variables (yes/no). The sum of six skinfold thicknesses and waist circumference (WC) values were the main body fatness variables. RESULT Skinfolds and WC values were lower in adolescents who reported consumption of mid-morning snack, afternoon snack, more than four meals per day, and an adequate speed of eating, independently of participation in LTPA. Moreover, a beneficial influence of breakfast consumption on skinfolds and WC values was observed in those adolescent boys who did not participate in LTPA (p for interactions = .044 and .040, respectively). CONCLUSIONS In Spanish adolescents, certain healthy dietary habits (i.e., mid-morning snack, afternoon snack, > 4 meals per day, adequate eating speed) are associated with lower body fatness, independently of engaging in LTPA. In addition, among boys with non-LTPA, those who skipped breakfast showed the highest body fatness values, indicating a beneficial influence of daily breakfast on body fat in this particular group.

Dehydroepiandrosterone modifies rat fatty acid composition of serum and different adipose tissue depots and lowers serum insulin levels

Dehydroepiandrosterone (DHEA) is reported to exert beneficial effects, such as protection from cardiovascular risk and lowering serum insulin levels. Adipose tissue (AT) is a target for DHEA actions, and the hormone can also affect hepatic fatty acid (FA) metabolism. FAs are involved in the development of insulin resistance; thus, there might be a relationship between DHEA, FA, and insulin. However, few data are available regarding DHEA and FA composition, especially concerning AT. Seventeen-month old female Sprague-Dawley rats (n=11; controls: n=10) were treated with DHEA (0.5% w/w in the diet) for 13 weeks, after which serum, periovarian, mesenteric, s.c., and brown AT were analyzed for FA composition. DHEA treatment resulted in significant changes in FA profiles in serum and adipose depots, like reduced 16:1n-7 (s.c. and brown AT; P<0.01), elevated n-9 monounsaturated FA (serum and s.c. AT; P<0.05), diminished n-6 polyunsaturated FA (PUFA; general; P<0.05) and increased n-3 PUFA (brown AT; P<0.01), along with lower n-6/n-3 ratios (s.c. and brown AT; P<0.05, P<0.01 respectively). DHEA modified estimates of desaturase activities, decreasing stearoyl-CoA-desaturase markers in s.c., and brown AT (P<0.05) and increasing those of delta-6-desaturase in serum and AT (P<0.05). In addition, DHEA-treated rats showed lower serum insulin levels (P<0.05). We have demonstrated for the first time that DHEA induces significant modifications in AT fatty acid composition in vivo, mainly concerning unsaturated FAs, and changes occurred in a tissue-dependent manner. We propose that these changes may be related to the capacity of DHEA to lower serum insulin levels.

Socioeconomic factors are associated with folate and vitamin B12 intakes and related biomarkers concentrations in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence study

Because socioeconomic factors (SEFs) may influence dietary quality and vitamin intakes, this study aimed to examine associations between socioeconomic factors and folate and vitamin B12 intakes as well as their related biomarkers in the Healthy Lifestyle in Europe by Nutrition in Adolescence study. Vitamin intakes were obtained from two 24-hour recalls in 2253 participants (47% males). Vitamin B biomarkers were assessed in a subsample of 977 participants (46% males). Socioeconomic factors were assessed by questionnaire, and 1-way analysis of covariance and linear regression analysis were applied. For males and females, mean intakes of folate were 211.19 and 177.18 μg/d, and for vitamin B12, 5.98 and 4.54 μg/d, respectively. Levels of plasma folate, red blood cell folate, serum B12, and holotranscobalamin were 18.74, 807.19, 330.64, and 63.04 nmol/L in males, respectively, and 19.13, 770.16, 377.9, and 65.63 nmol/L in females, respectively. Lower folate intakes were associated with several SEFs, including maternal and paternal education in both sexes. Regarding folate biomarkers, lower plasma folate intakes were associated with single/shared care in males and with lower paternal occupation in females. Lower vitamin B12 intakes were associated with almost all the studied SEFs, except paternal occupation in both sexes. In females, when considering vitamin B12 biomarkers, lower plasma vitamin B12 was associated with lower maternal education and occupation, and lower holotranscobalamin was associated with lower maternal education and lower paternal occupation. In conclusion, from the set of socioeconomic determinants studied in a sample of European adolescents, maternal education and paternal occupation were more consistently associated with folate and vitamin B12 intakes and biomarkers concentrations.

Television viewing time and risk of eating disorders in Spanish adolescents: AVENA and AFINOS studies

Effective preventive interventions for both eating disorders and obesity in adolescence should be focused on shared risk factors. We analyzed the association between television (TV) viewing time and the risk of eating disorders, as well as the potential role of obesity in this association.