Oxidative stress and immunosenescence in spleen of obese mice can be reversed by 2-hydroxyoleic acid.

NEW FINDINGS: What is the central question of this study? Evidence is growing for the link between obesity, immune dysfunction and oxidative stress, but it is still not known how the properties and functions of the spleen and splenic leucocytes are affected. What is the main finding and its importance? Obesity led to premature immunosenescence, manifested as oxidative stress and changes in leucocyte functions in mouse spleen. The oleic acid derivative 2-hydroxyoleate and, to a lesser extent, a combination of eicosapentaenoic and docosahexaenoic acids could reverse most of the observed alterations, suggesting a potential therapeutic tool for obesity-related immune dysfunction and redox imbalance. We aimed to investigate the effects of obesity on oxidative stress and leucocyte function in the mouse spleen and to assess whether supplementation with 2-hydroxyoleic acid (2-OHOA) or n-3 polyunsaturated fatty acids (PUFAs) could reverse those effects. Female ICR/CD1 mice (8 weeks old, n = 24) received an obesogenic diet (22% fat for 4 weeks and 60% fat for 14 weeks). After 6 weeks, mice were divided into the following three groups (n = 8 per group): no supplementation; 2-OHOA supplementation (1500 mg kg-1 of diet); and n-3 PUFA supplementation (eicosapentaenoic acid and docosahexaenoic acid, 1500 + 1500 mg kg-1 of diet). Eight mice were fed the standard diet for the whole duration of the study (control group). At the end of the experiment, the following variables were assessed in spleens: levels of reduced (GSH) and oxidized glutathione (GSSG), GSH/GSSG, xanthine oxidase activity, lipid peroxidation, lymphocyte chemotaxis, natural killer activity and mitogen (concanavalin A and lipopolysaccharide)-induced lymphocyte proliferation. Obese animals presented higher GSSG levels (P = 0.003), GSSG/GSH ratio (P = 0.013), lipid peroxidation (P = 0.004), xanthine oxidase activity (P = 0.015) and lymphocyte chemotaxis (P < 0.001), and lower natural killer activity (P = 0.003) and proliferation in response to concanavalin A (P < 0.001) than control mice. 2-Hydroxyoleic acid totally or partly reversed most of the changes (body weight, fat content, GSSG levels, GSH/GSSG, lipid peroxidation, chemotaxis and proliferation, all P < 0.05), whereas n-3 PUFAs reversed the increase in xanthine oxidase activity (P = 0.032). In conclusion, 2-OHOA or, to a lesser extent, n-3 PUFAs could ameliorate the oxidative stress and alteration of leucocyte function in the spleens of obese mice. Our findings support a link between obesity and immunosenescence and suggest a potential therapeutic tool for obesity-related immune dysfunction.

Influence of sex, age, pubertal maturation and body mass index on circulating white blood cell counts in healthy European adolescents­the HELENA study.

UNLABELLED: Percentiles 10th, 25th, 50th, 75th and 90th are presented for circulating white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils and basophils in healthy European adolescents (12.5-17.5 years, n = 405, 48.9% boys), considering age, sex, puberty and body mass index (BMI). CD3(+) (mature T cells), CD4(+) (T helper), CD8(+) (T cytotoxic), CD16(+)56(+) (natural killer), CD19(+) (B cells), CD3(+)CD45RA(+), CD4(+)CD45RA(+), CD8(+)CD45RA(+) (naïve), CD3(+)CD45RO(+), CD4(+)CD45RO(+) and CD8(+)CD45RO(+) (memory) lymphocytes were also analysed by immunophenotyping. Girls presented higher WBC, neutrophil, CD3(+)CD45RO(+) and CD4(+)CD45RO(+) cell counts and CD3(+)/CD19(+) ratio, and lower CD3(+)CD45RA(+) and CD4(+)CD45RA(+) counts than boys. Age was associated with higher neutrophil counts and CD3(+)/CD19(+), and lower CD19(+) counts; in boys, with lower CD3(+)CD45RA(+), CD4(+)CD45RA(+) and CD8(+)CD45RA(+) counts as well; in girls, with higher WBC, CD3(+)CD45RO(+) and CD4(+)CD45RO(+) counts. Pubertal maturation in boys was associated with lower WBC and lymphocyte counts; in girls, with higher basophil, CD3(+)CD45RO(+) and CD4(+)CD45RO(+) values. BMI was associated with higher WBC counts; in boys, also with higher lymphocyte counts; in girls, with higher neutrophil, CD4(+), CD3(+)CD45RO(+) and CD4(+)CD45RO(+) counts. CONCLUSION: Our study provides normative values for circulating immune cells in adolescents, highlighting the importance of considering sex, age, pubertal maturation and BMI when establishing reference ranges for WBC in paediatric populations.

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

BACKGROUND: 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. METHODS: The sample consisted of a total of 3458 Spanish adolescents, aged 13-18.5 years, from the Food and Assessment of the Nutritional Status of Adolescents (AVENA) and Physical Activity as a Preventive Measure of the Development of Overweight, Obesity, Allergies, Infections, and Cardiovascular Risk Factors in Adolescents (AFINOS) studies. Adolescents' TV time was assessed by self-report. Body mass index was calculated and the adolescents were classified into non-overweight and overweight-obesity. The risk of eating disorders was evaluated using the SCOFF questionnaire. RESULTS: Adolescents who watched TV >1 h/day had a higher risk for eating disorders, compared with those adolescents who watch TV <1 h/day. Also, overweight-obese adolescents had a higher risk for eating disorders than those who were non-overweight. Analyses across groups of TV viewing time and weight status showed similar trends, so that the higher the time spent in TV viewing, the higher the risk of eating disorders, regardless of weight status. CONCLUSIONS: TV viewing time might be a focal point for prevention of both eating disorders and obesity in adolescence.

The association of appendicular lean mass and grip strength with low-density lipoprotein, very low-density lipoprotein, and high-density lipoprotein particle diameter: a Mendelian randomization study of the UK Biobank cohort.

Aims: Reduced muscle mass and reduced strength are frequently associated with both alterations in blood lipids and poorer cardiometabolic outcomes in epidemiological studies; however, a causal association cannot be determined from such observations. Two-sample Mendelian randomization (MR) was applied to assess the association of genetically determined appendicular lean mass (ALM) and handgrip strength (HGS) with serum lipid particle diameter. Methods and results: Mendelian randomization was implemented using summary-level data from the largest genome-wide association studies on ALM (n = 450 243), HGS (n = 223 315), and lipoprotein [low-density lipoprotein (LDL), very LDL (VLDL), and high-density lipoprotein (HDL)] particle diameters (n = 115 078). Inverse variance-weighted (IVW) method was used to calculate the causal estimates. Weighted median-based method, MR-Egger, and leave-one-out method were applied as sensitivity analysis. Greater ALM had a statistically significant positive effect on HDL particle diameter (MR-Egger: ß = 0.055, SE = 0.031, P = 0.081; IVW: ß = 0.068, SE = 0.014, P < 0.001) and a statistically significant negative effect on VLDL particle diameter (MR-Egger: ß = -0.114, SE = 0.039, P = 0.003; IVW: ß = -0.081, SE = 0.017, P < 0.001). Similarly, greater HGS had a statistically significant positive effect on HDL particle diameter (MR-Egger: ß = 0.433, SE = 0.184, P = 0.019; IVW: ß = 0.121, SE = 0.052, P = 0.021) and a statistically significant negative effect on VLDL particle diameter (MR-Egger: ß = -0.416, SE = 0.163, P = 0.011; IVW: ß = -0.122, SE = 0.046, P = 0.009). There was no statistically significant effect of either ALM or HGS on LDL particle diameter. Conclusion: There were potentially causal associations between both increasing ALM and HGS and increasing HDL particle size and decreasing VLDL particle size. These causal associations may offer possibilities for interventions aimed at improving cardiovascular disease risk profile.

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.

Acceptability of a high-protein Mediterranean-style diet and resistance exercise protocol for cardiac rehabilitation patients: Involving service users in intervention design using a mixed-methods participatory approach.

Background: Current cardiac rehabilitation (CR) practices focus on aerobic-style exercise with minimal nutrition advice. This approach may not be optimal for CR patients with reduced muscle mass and elevated fat mass. Higher protein, Mediterranean-style diets combined with resistance exercise (RE) may improve muscle mass and reduce the risk of future cardiovascular events, although such an approach is yet to be trialed in a CR population. Objective: We explored patient perspectives on the proposed design of a feasibility study. Patients reflected on the acceptability of a proposed high-protein Mediterranean-style diet and RE protocol, emphasizing research methodology and the acceptability of the proposed recipes and exercises. Design: We applied quantitative and qualitative (mixed methods) approaches. The quantitative approach involved an online questionnaire (n = 40) regarding the proposed study methodology and relevance. A subset of participants (n = 12) received proposed recipe guides and were asked to prepare several dishes and complete an online questionnaire regarding their experience. Another subset (n = 18) received links to videos of the proposed RE and completed a questionnaire regarding their impressions of them. Finally, semi-structured interviews (n = 7) were carried out to explore participants' impressions of the proposed diet and exercise intervention. Results: Quantitative data indicated a high level of understanding of the intervention protocol and its importance within the context of this research. There was a high degree of willingness to participate in all aspects of the proposed study (>90%). The trialed recipes were enjoyed and found to be easy to make by a majority of participants (79 and 92.1%, respectively). For the proposed exercises 96.5% of responses agreed they would be willing to perform them and, 75.8% of responses agreed they would enjoy them. Qualitative analysis revealed that participants viewed the research proposal, diet, and exercise protocol in a positive light. The research materials were considered appropriate and well explained. Participants suggested practical recommendations for improving recipe guides and requested more individual-focused exercise recommendations, and more information on the specific health benefits of the diet and exercise protocols. Conclusion: The study methodology and the specific dietary intervention and exercise protocol were found to be generally acceptable with some suggested refinements.

Impact of COVID-19 lockdown restrictions on cardiac rehabilitation participation and behaviours in the United Kingdom.

BACKGROUND: COVID-19 lockdown measures led to the suspension of centre-based cardiac rehabilitation (CR). We aimed to describe the impact of lockdown on CR behaviours and perceptions of efficacy in a sample of CR participants. METHODS: An online survey was conducted amongst CR participants from May to October 2020, COVID-19-related lockdown restrictions. Anthropometric data, participant-determined levels of motivation and self-perceived efficacy, CR practices etc., pre- and post-lockdown, were collected. RESULTS: The probability of practicing CR in public gyms and hospitals decreased 15-fold (47.2% pre-, 5.6% post-lockdown; OR[95% CI] 0.065[0.013; 0.318], p < 0.001), and 34-fold (47.2% pre, 2.8% post; OR[95% CI] 0.029[0.004; 0.223], p < 0.001), respectively. Amongst participants, 79.5% indicated that their CR goals had changed and were 78% less likely to engage in CR for socialization after lockdown (47.2% pre, 16.7% post; OR[95% CI] 0.220[0.087; 0.555]; p = 0.002). The probability of receiving in-person supervision decreased by 90% (94.4% pre, 16.7% post; OR[95% CI] 0.011[0.002; 0.056]), while participants were almost 7 times more likely to use online supervision (11.1% pre, 44.4% post; OR[95% CI] 6.824[2.450; 19.002]) (both p < 0.001). Fifty percent indicated that their enjoyment of CR was lower than before lockdown and 27.8% reported they would be less likely to continue with CR in the newer format. CONCLUSIONS: Lockdown was associated with considerable changes in how CR was practiced, motivation levels and willingness to continue with CR. Further research is warranted to develop and improve strategies to implement in times when individuals cannot attend CR in person and not only during pandemics.

Protein interventions augment the effect of resistance exercise on appendicular lean mass and handgrip strength in older adults: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Increased protein intake is suggested as a strategy to slow or reverse the loss of muscle mass and strength observed in sarcopenia, but results from studies that directly tested this possibility have been inconsistent. OBJECTIVES: We assessed the evidence on the effects of whole protein supplementation or higher-protein diets, without the use of amino acids or supplements known to stimulate hypertrophy, alone or in combination with resistance exercise (RE) interventions, on lean body mass (LBM) and strength in older adults. METHODS: A systematic search was conducted using PubMed, Medline, Web of Science, and Cochrane CENTRAL databases from January 1990 to July 2021. Randomized controlled trials that assessed the effects of protein supplementation and/or higher-protein dietary interventions in older adults (mean age ≥50 y) on total LBM, appendicular lean mass (ALM), and handgrip (HG) and knee extension (KE) strength were included. RESULTS: Twenty-eight studies were identified. In pooled analysis, compared with lower protein controls, protein supplementation did not have a significant positive effect on total LBM [weighted mean difference in change (WMD): 0.34; 95% CI: -0.21, 0.89; I2 = 90.01%], ALM (WMD: 0.4; 95% CI: -0.01, 0.81; I2 = 90.38%), HG strength (WMD: 0.69; 95% CI: -0.69, 2.06; I2 = 94.52%), or KE strength (WMD: 1.88; 95% CI: -0.6, 4.35; I2 = 95.35%). However, in interventions that used also RE, statistically significant positive effects of protein were observed for ALM (WMD: 0.54; 95% CI: 0.03, 1.05; I2 = 89.76%) and HG (WMD: 1.71; 95% CI: 0.12, 3.30; I2 = 88.71%). Meta-regression revealed no significant association between age, per-meal protein dose, duration, and baseline protein intake with change in any outcome. Subgroup analysis revealed the statistically significant effects on ALM occurred only in sarcopenic/frail populations (WMD: 0.88; 95% CI: 0.51, 1.25; I2 = 79.0%). Most studies (n = 22) had some risk of bias. CONCLUSIONS: In older adults performing RE, increased protein intake leads to greater ALM and HG strength compared with lower protein controls. Without RE, protein has no additional benefit on changes in total LBM, ALM, or HG strength.

Feasibility of a high-PRotein Mediterranean-style diet and resistance Exercise in cardiac Rehabilitation patients with sarcopenic obesity (PRiMER): Study protocol for a randomised control trial.

BACKGROUND: Cardiac rehabilitation (CR) is an essential component of long-term recovery following a cardiac event. Typical CR may not be optimal for patients presenting with sarcopenic obesity (SO) who present with reduced muscle mass and elevated adipose tissue, and may indicate greater cardiovascular disease (CVD) risk. Resistance exercise and high-protein diets are known to increase muscle mass, while Mediterranean-style diets have been shown to reduce CVD risk. A high-protein Mediterranean-style diet combined with resistance exercise intervention is yet to be trialled in cardiac rehabilitation populations. OBJECTIVES: Primary outcome: to determine the feasibility of such an intervention by investigating the perceptions, acceptance and adherence to a resistance exercise protocol and high-protein Mediterranean style diet in a UK cardiac rehabilitation population with SO. Secondary outcome: to trial this protocol ahead of a fully powered clinical study. METHODS: Eligible cardiac rehabilitation patients will be randomised to one of the following: 1) a control group (standard CR), 2) high-protein Mediterranean-style diet, 3) resistance exercise group, or 4) both high-protein Mediterranean-style diet and resistance exercise group. The pilot study will last 12 weeks. Measures of body composition (dual energy x-ray absorptiometry) grip strength, CVD risk (e.g., fasting triglycerides, glucose, cholesterol) and dietary adherence will be assessed at baseline and after 12 weeks. To compare groups, a mixed model ANOVA (time x intervention) will be performed. Patient participant involvement throughout the development of this project will be used to determine the feasibility of a future, fully powered, randomised control trial. A feasibility questionnaire will help establish the proportion of eligible participants, their willingness to be randomised, response rates, and ethical considerations. Furthermore, focus groups, food tasting and telephone interviews will be conducted to assess the acceptability of recipes and exercise protocols provided. DISCUSSION: This pilot trial will determine whether a fully powered, multi-centred randomised control trial in CR patients with SO can be implemented. The information received from patient involvement will be invaluable for identifying possible barriers to participation and tailoring interventions to participant needs, helping to increase the likelihood of long-term compliance to health-promoting lifestyle changes. REGISTRATION: This study is registered at clinicaltrials.gov (NCT04272073), registered on 17/02/2020, https://clinicaltrials.gov/ct2/show/NCT04272073. DATE AND VERSION: 28/12/20 version 3.0.

Hypoxia stimulates lactate release and modulates monocarboxylate transporter (MCT1, MCT2, and MCT4) expression in human adipocytes.

Hypoxia modulates white adipose tissue function, and this includes stimulating glucose uptake and the expression of facilitative glucose transporters (particularly GLUT1) in adipocytes. This study has examined the effect of hypoxia on lactate release from adipocytes and whether the monocarboxylate transporters that mediate lactate transport (MCTs1-4) are expressed in human adipocytes and are induced by low O(2) tension. Exposure of human Simpson-Golabi-Behmel syndrome adipocytes to 1% O(2) for 24 h resulted in increased lactate release (2.3-fold) compared with cells in normoxia (21% O(2)). Screening by reverse transcription polymerase chain reaction indicated that the genes encoding MCT1, MCT2, and MCT4 are expressed in human adipose tissue, and in adipocytes and preadipocytes in culture. Hypoxia (48 h) increased MCT1 (8.5-fold) and MCT4 (14.3-fold) messenger RNA (mRNA) levels in human adipocytes, but decreased MCT2 mRNA (fourfold). MCT1 protein level was also increased (2.7-fold at 48 h) by hypoxia, but there was no change in MCT4 protein. The changes in MCT gene expression induced by hypoxia were reversed on return to normoxia. Treatment with the hypoxia mimetic CoCl(2) resulted in up-regulation of MCT1 (up to twofold) and MCT4 (fivefold) mRNA level, but there was no significant effect on MCT2 expression. It is concluded that hypoxia increases lactate release from adipocytes and modulates MCT expression in a type-specific manner, with MCT1 and MCT4 expression being hypoxia-inducible transcription factor-1 (HIF-1) dependent. Increased lactate production and monocarboxylate transporter expression are likely to be key components of the adaptive response of adipocytes to low O(2) tension as adipose tissue mass expands in obesity.

Sarcopenia during COVID-19 lockdown restrictions: long-term health effects of short-term muscle loss.

The COVID-19 pandemic is an extraordinary global emergency that has led to the implementation of unprecedented measures in order to stem the spread of the infection. Internationally, governments are enforcing measures such as travel bans, quarantine, isolation, and social distancing leading to an extended period of time at home. This has resulted in reductions in physical activity and changes in dietary intakes that have the potential to accelerate sarcopenia, a deterioration of muscle mass and function (more likely in older populations), as well as increases in body fat. These changes in body composition are associated with a number of chronic, lifestyle diseases including cardiovascular disease (CVD), diabetes, osteoporosis, frailty, cognitive decline, and depression. Furthermore, CVD, diabetes, and elevated body fat are associated with greater risk of COVID-19 infection and more severe symptomology, underscoring the importance of avoiding the development of such morbidities. Here we review mechanisms of sarcopenia and their relation to the current data on the effects of COVID-19 confinement on physical activity, dietary habits, sleep, and stress as well as extended bed rest due to COVID-19 hospitalization. The potential of these factors to lead to an increased likelihood of muscle loss and chronic disease will be discussed. By offering a number of home-based strategies including resistance exercise, higher protein intakes and supplementation, we can potentially guide public health authorities to avoid a lifestyle disease and rehabilitation crisis post-COVID-19. Such strategies may also serve as useful preventative measures for reducing the likelihood of sarcopenia in general and in the event of future periods of isolation.

2-OHOA supplementation reduced adiposity and improved cardiometabolic risk to a greater extent than n-3 PUFA in obese mice.

OBJECTIVE: We aimed to assess whether 2-hydroxyoleic acid (2-OHOA) and n-3 polyunsaturated fatty acids (PUFA) could counteract changes on adipokine secretion and cardiometabolic risk biomarkers associated with high-fat diet-induced obesity in mice. METHODS: Female ICR/CD1 mice (8 weeks old) were divided into four groups receiving different diets (n=8/group): (1) standard chow (control) for 18 weeks; (2) 22% fat for 4 weeks + 60% fat for 14 weeks (obesogenic diet, OD); 3) OD + 2-OHOA (1500mgkg-1 diet) for the last 6 weeks (ODHO); and 4) OD+n-3 PUFA (eicosapentaenoic+docosahexaenoic acids, 1500+1500mgkg-1 diet) for the last 6 weeks (OD-N3). After 18 weeks, body weight, periovarian visceral fat, heart and liver weights were measured, as well as cardiometabolic parameters (systolic and diastolic blood pressure, blood glucose, insulin, HOMA index, triglycerides, total cholesterol, apolipoproteins A1 and E), plasma adipokines and inflammatory proteins (leptin, adiponectin, plasminogen activator inhibitor 1 [PAI1], soluble E-selectin [sE-selectin], matrix metalloproteinase-9 [MMP-9], fibrinogen, soluble intercellular adhesion molecule [sICAM] and soluble vascular adhesion molecule [sVCAM]), and secretion of pro-inflamatory cytokines and inflammatory biomarkers from periovarian adipocytes. RESULTS: OD mice had greater body and heart weights, and plasma leptin, and lower adiponectin and resistin secretion from adipocytes. Supplementation with 2-OHOA reduced body and heart weights, blood pressure, triglycerides and leptin, and restored adiponectin and resistin secretion, while n-3 PUFA only reduced triglyceride levels (all P<0.05). CONCLUSION: 2-OHOA supplementation was more effective in reducing adiposity, modulating adipokine secretion and ameliorating cardiometabolic risk than n-3 PUFA.

Role of DHEA-S on body fat distribution: gender- and depot-specific stimulation of adipose tissue lipolysis.

The objective of this work was to study the possible impact of DHEA-S on body fat distribution and the specific action of the hormone on lipolysis from visceral and subcutaneous human adipose tissue. First, a clinical evaluation was performed in 84 obese patients (29 men, 55 women), measuring serum DHEA-S, computed tomography (CT) anthropometric parameters of abdominal fat distribution. In a second experiment, subcutaneous and visceral adipose tissue samples were obtained from 20 obese patients (10 men, 10 women) and cultured in vitro under stimulation with DHEA-S to further assess a possible effect of this hormone on adipose tissue lipolysis. Serum DHEA-S was inversely and specifically associated with visceral fat area (VA) as assessed by CT in men and with waist-to-hip ratio in women. In vitro, DHEA-S increased lipolysis in women's subcutaneous adipose tissue at 2 h, while in men, the effect was evident in visceral tissue and after 24 h of treatment. In conclusion, DHEA-S contributes to gender-related differences in body fat distribution probably by a differential lipolytic action. We have demonstrated for the first time in vitro that DHEA-S stimulates lipolysis preferably in subcutaneous fat in women and in visceral fat in men.

Adiponectin is involved in the protective effect of DHEA against metabolic risk in aged rats.

The aim of the present work was to analyze the effect of dehydroepiandrosterone (DHEA) on several metabolic risk factors, including cardiovascular health and insulin resistance, in aged rats submitted to a high-fat diet. For that, weaned rats were fed on a high-fat diet until 20 months of age. In the last 13 weeks of life, a group (n=11) received the diet supplemented with DHEA (0.5%, w/w), serving the rest (n=10) as controls. Body weight, body fat, serum lipids (triglycerides, total cholesterol and non-esterified fatty acids (NEFA)), HOMA index, n-6/n-3 polyunsaturated fatty acid (PUFA) ratios, serum adiponectin, leptin, resistin and TNF-alpha, as well as adiponectin expression in adipose tissue, were measured. A stepwise discriminant test was used to analyze these variables, and an index of overall metabolic risk was generated from them. DHEA treatment resulted in a significantly lower overall metabolic risk index, as generated by the discriminant test (P<0.01). The DHEA group had lower body fat and n-6/n-3 polyunsaturated fatty acid (PUFA) ratios than the control group (P<0.01), and the same trends were observed for serum cholesterol, triglycerides and HOMA index; in contrast, adiponectin expression in adipose tissue increased in DHEA-treated rats (P<0.05). The discriminant analysis revealed that adiponectin, both from serum and adipose tissue, was the most influencing factor, followed by n-6/n-3 ratios in adipose tissue, and by body fat. Our results then suggest that adiponectin is involved in the protective effect of DHEA against metabolic risk demonstrated in the present work.

Resistance to dietary obesity in rats given different high-energy diets.

Susceptibility to dietary obesity was studied in Wistar and Sprague-Dawley rats submitted to different high-energy diets. Experiment 1: female Sprague-Dawley rats were fed chow (n = 6) or a high-fat diet (n = 12) for 22 weeks. Experiment 2: Wistar rats were fed chow or a high-fat diet, and Sprague-Dawley rats were given chow, high-fat, sweet condensed milk, or cafeteria diets, for eight weeks (6 animals per group). Food intake and body weight were recorded weekly. Adipose tissue was collected from periovarian, mesenteric, and subcutaneous regions and adipocytes were isolated and measured. Both strains showed similar energy intake and body weight gain. Wistar rats reached greater final body fat contents than Sprague-Dawley rats, regardless of the type of diet. However, resistance to dietary obesity was found in 100% of cases in both experiments. None of the diets succeeded in increasing body fat accumulation when compared to control groups. All adipose tissue locations were equally unaffected, with periovarian fat cells being larger than those in mesenteric and subcutaneous regions in all the groups. In view of the strong resistance to obesity observed in rats, it should be important for researchers to transmit the difficulties of inducing dietary obesity in these animals, in order to prevent bias in science interpretation.

The Role of Probiotics on the Microbiota: Effect on Obesity.

The microbiota and the human host maintain a symbiotic association. Nowadays, metagenomic analyses are providing valuable knowledge on the diversity and functionality of the gut microbiota. However, with regard to the definition of a "healthy microbiota" and the characterization of the dysbiosis linked to obesity, there is still not a clear answer. Despite this fact, attempts have been made to counteract obesity through probiotic supplementation. A literature search of experimental studies relevant to the topic was performed in PubMed database with the keywords "probiotic" and "obesity" and restricted to those with "Lactobacillus" or "Bifidobacterium" in the title. So far, evidence of an antiobesity effect of different lactobacilli and bifidobacteria has been mainly obtained from animal models of dietary-induced obesity. Using these experimental models, a substantial number of studies have reported reductions in weight gain and, in particular, fat tissue mass at different locations following administration of bacteria, as compared with controls. Antiatherogenic and anti-inflammatory effects-including regulation of expression of lipogenic and lipolytic genes in the liver, reduction in liver steatosis, improvement of blood lipid profile and glucose tolerance, decreased endotoxemia, and regulation of inflammatory pathways-are also reported in many of them. The number of human studies focused on probiotic administration for obesity management is still very scarce, and it is too soon to judge their potential efficacy, especially when considering the fact that the actions of probiotics are always strain specific and the individual response varies according to intrinsic factors, the overall composition of diet, and their interactions.

Dietary lipid intake only partially influences variance in serum phospholipid fatty acid composition in adolescents: impact of other dietary factors.

The present study aimed to assess the correlation between food and fatty acid (FA) intake and the serum phospholipid (PL) FA status in European adolescents and explored the percentage of variation in serum PL FA that could be attributed to dietary habits. Participants included 528 adolescents recruited in the HELENA Study. Dietary intake was assessed by two, self-administered, non-consecutive 24-h recalls. PL FA concentrations were measured in fasting venous serum samples. Reduced rank regressions were applied to examine the combined effect of food intakes. Results indicated that the variance in serum PL FA in adolescents, that could be explained by diet varied from 7.0% for MUFA to 14.2% for n-3FA. The variance in the long-chain n-3FA was mainly explained by fish intake but also by coffee and tea consumption. In conclusion this study indicated that dietary intake influences the serum PL FA status to a limited amount but that also other factors interfere. However, dietary intake is important as it is among those factors that could be modified. Furthermore, the results suggest that the overall dietary habits should be considered instead of only the consumption of single foods or nutrients, as the medium of the food or concomitant intake of foods and nutrients might interact and as such influence absorption or metabolism.

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.

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.

Fatty acids and hypoxia stimulate the expression and secretion of the adipokine ANGPTL4 (angiopoietin-like protein 4/ fasting-induced adipose factor) by human adipocytes.

BACKGROUND/AIMS: Hypoxia occurs in white adipose tissue in obesity, modulating the expression and release of specific inflammation-related adipokines. ANGPTL4 (angiopoietin-like protein 4/fasting-induced adipose factor), which is implicated in angiogenesis, lipid metabolism and glucose homeostasis, is a major hypoxia-sensitive gene; recent studies indicate that ANGPTL4 expression is also regulated by fatty acids. We have examined the effects of hypoxia and fatty acids, alone and together, on the expression and release of ANGPTL4 by human adipocytes. METHODS: Human adipocytes were differentiated and incubated with fatty acids (250 µM) in normoxia (21% O(2)) or hypoxia (1% O(2)). ANGPTL4 mRNA was measured by real-time PCR and the protein in the medium determined by ELISA. RESULTS: In normoxia, ANGPTL4 gene expression was upregulated by palmitic, oleic, arachidonic and eicosapentaenoic acids, and ANGPTL4 release was increased. In contrast, there was no effect of lauric or myristic acids. Hypoxia alone increased the expression and secretion of ANGPTL4, and lauric, myristic, arachidonic and eicosapentaenoic acids each further increased expression and release in hypoxic adipocytes. CONCLUSION: The expression and secretion of ANGPTL4 by human adipocytes is upregulated by both hypoxia and fatty acids. The stimulatory effect of fatty acids on ANGPTL4 production is augmented under hypoxic conditions.