J. Alfredo Martínez

Diets with high or low protein content and glycemic index for weight-loss maintenance

BACKGROUND Studies of weight-control diets that are high in protein or low in glycemic index have reached varied conclusions, probably owing to the fact that the studies had insufficient power. METHODS We enrolled overweight adults from eight European countries who had lost at least 8% of their initial body weight with a 3.3-MJ (800-kcal) low-calorie diet. Participants were randomly assigned, in a two-by-two factorial design, to one of five ad libitum diets to prevent weight regain over a 26-week period: a low-protein and low-glycemic-index diet, a low-protein and high-glycemic-index diet, a high-protein and low-glycemic-index diet, a high-protein and high-glycemic-index diet, or a control diet. RESULTS A total of 1209 adults were screened (mean age, 41 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 34), of whom 938 entered the low-calorie-diet phase of the study. A total of 773 participants who completed that phase were randomly assigned to one of the five maintenance diets; 548 completed the intervention (71%). Fewer participants in the high-protein and the low-glycemic-index groups than in the low-protein-high-glycemic-index group dropped out of the study (26.4% and 25.6%, respectively, vs. 37.4%; P=0.02 and P=0.01 for the respective comparisons). The mean initial weight loss with the low-calorie diet was 11.0 kg. In the analysis of participants who completed the study, only the low-protein-high-glycemic-index diet was associated with subsequent significant weight regain (1.67 kg; 95% confidence interval [CI], 0.48 to 2.87). In an intention-to-treat analysis, the weight regain was 0.93 kg less (95% CI, 0.31 to 1.55) in the groups assigned to a high-protein diet than in those assigned to a low-protein diet (P=0.003) and 0.95 kg less (95% CI, 0.33 to 1.57) in the groups assigned to a low-glycemic-index diet than in those assigned to a high-glycemic-index diet (P=0.003). The analysis involving participants who completed the intervention produced similar results. The groups did not differ significantly with respect to diet-related adverse events. CONCLUSIONS In this large European study, a modest increase in protein content and a modest reduction in the glycemic index led to an improvement in study completion and maintenance of weight loss. (Funded by the European Commission; ClinicalTrials.gov number, NCT00390637.).

Obesity and the metabolic syndrome: role of different dietary macronutrient distribution patterns and specific nutritional components on weight loss and maintenance

Weight loss and subsequent body weight maintenance are difficult for obese individuals despite the wide variety of dietary regimens and approaches. A substantial body of scientific evidence has shown that by simply varying the macronutrient distribution and composition of dietary factors, weight losses of varying amounts, longer-term body weight maintenance periods, better appetite regulation, and changes in features of the metabolic syndrome can be achieved. At present, renewed efforts are underway to increase the protein content of weight-loss diets, simultaneously restrict fat consumption to no more than 30%, favor polyunsaturated fat, have carbohydrates account for between 40 and 50% of total energy intake, and promote the consumption of low-glycemic foods. The present article reviews the scientific evidence for the effects of several dietary manipulations and sustainable strategies for weight loss and body weight stability as well as for treating specific features of the metabolic syndrome.

Role of omega-3 fatty acids in obesity, metabolic syndrome, and cardiovascular diseases: a review of the evidence

The present review aims to illustrate current knowledge about the efficacy of omega-3 long-chain polyunsaturated fatty acids (n−3 LC-PUFAs) in treating/preventing several metabolic pathologies. We reviewed systematically the published evidence on the effectiveness of n−3 LC-PUFAs fish consumption or n−3 LC-PUFAs supplementation on prevention/treatment of obesity, metabolic syndrome, and cardiovascular diseases. Most of the reviewed studies were randomized-controlled interventional trials, although some relevant prospective and cross-sectional studies as well as some meta-analysis were also reviewed. Supplementation with n−3 LC-PUFAs might improve some obesity-associated metabolic syndrome features such as insulin resistance, hypertension and dyslipidemia by decreasing plasma triglycerides. Moreover, the blood pressure-lowering and anti-inflammatory properties of these fatty acids and their benefits in vascular function might confer cardioprotection. However, the efficacy of n−3 LC-PUFA on reducing myocardial infarction, arrhythmia, cardiac and sudden death, or stroke is controversial. Due to the beneficial actions of n−3 LC-PUFAs, several worldwide government and health organizations have established some recommendations of n−3 LC-PUFAs intake for groups of population. In general, the recommended levels for diseases prevention are lower than those advised for particular treatments. However, more clinical trials are necessary to recommend the most effective dosages and formulas (type of n−3 LC-PUFA, EPA/DHA ratio) for specific pathologies.

Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-α

n-3 PUFA have shown potential anti-obesity and insulin-sensitising properties. However, the mechanisms involved are not clearly established. The aim of the present study was to assess the effects of EPA administration, one of the n-3 PUFA, on body-weight gain and adiposity in rats fed on a standard or a high-fat (cafeteria) diet. The actions on white adipose tissue lipolysis, apoptosis and on several genes related to obesity and insulin resistance were also studied. Control and cafeteria-induced overweight male Wistar rats were assigned into two subgroups, one of them daily received EPA ethyl ester (1 g/kg) for 5 weeks by oral administration. The high-fat diet induced a very significant increase in both body weight and fat mass. Rats fed with the cafeteria diet and orally treated with EPA showed a marginally lower body-weight gain (P = 0.09), a decrease in food intake (P < 0.01) and an increase in leptin production (P < 0.05). EPA administration reduced retroperitoneal adipose tissue weight (P < 0.05) which could be secondary to the inhibition of the adipogenic transcription factor PPARgamma gene expression (P < 0.001), and also to the increase in apoptosis (P < 0.05) found in rats fed with a control diet. TNFalpha gene expression was significantly increased (P < 0.05) by the cafeteria diet, while EPA treatment was able to prevent (P < 0.01) the rise in this inflammatory cytokine. Adiposity-corrected adiponectin plasma levels were increased by EPA. These actions on both TNFalpha and adiponectin could explain the beneficial effects of EPA on insulin resistance induced by the cafeteria diet.

Weight Gain Induced by High-Fat Feeding Involves Increased Liver Oxidative Stress

Objective: To assess the effects of high‐fat feeding on white adipose tissue gene expression and liver oxidative stress.

A dual epigenomic approach for the search of obesity biomarkers: DNA methylation in relation to diet-induced weight loss

Epigenetics could help to explain individual differences in weight loss after an energy‐restriction intervention. Here, we identify novel potential epigenetic biomarkers of weight loss, comparing DNA methylation patterns of high and low responders to a hypocaloric diet. Twenty‐five overweight or obese men participated in an 8‐wk caloric restriction intervention. DNA was isolated from peripheral blood mononuclear cells and treated with bisulfite. The basal and endpoint epigenetic differences between high and low responders were analyzed by methylation microarray, which was also useful in comparing epigenetic changes due to the nutrition intervention. Subsequently, MALDI‐TOF mass spectrometry was used to validate several relevant CpGs and the surrounding regions. DNA methylation levels in several CpGs located in the ATP10A and CD44 genes showed statistical baseline differences depending on the weight‐loss outcome. At the treatment endpoint, DNA methylation levels of several CpGs on the WT1 promoter were statistically more methylated in the high than in the low responders. Finally, different CpG sites from WT1 and ATP10A were significantly modified as a result of the intervention. In summary, hypocaloricdiet‐induced weight loss in humans could alter DNA methylation status of specific genes. Moreover, baseline DNA methylation patterns may be used as epigenetic markers that could help to predict weight loss.—Milagro, F. I., Campion, J., Cordero, P., Goyenechea, E., Gómez‐Uriz, A. M., Abete, I., Zulet, M. A., Martínez, J. A. A dual epigenomic approach for the search of obesity biomarkers: DNA methylation in relation to diet‐induced weight loss. FASEB J. 25, 1378–1389 (2011). www.fasebj.org

Interaction between genes and lifestyle factors on obesity.

Obesity originates from a failure of the body-weight control systems, which may be affected by changing environmental influences. Basically, the obesity risk depends on two important mutually-interacting factors: (1) genetic variants (single-nucleotide polymorphisms, haplotypes); (2) exposure to environmental risks (diet, physical activity etc.). Common single-nucleotide polymorphisms at candidate genes for obesity may act as effect modifiers for environmental factors. More than 127 candidate genes for obesity have been reported and there is evidence to support the role of twenty-two genes in at least five different populations. Gene-environment interactions imply that the synergy between genotype and environment deviates from either the additive or multiplicative effect (the underlying model needs to be specified to appraise the nature of the interaction). Unravelling the details of these interactions is a complex task. Emphasis should be placed on the accuracy of the assessment methods for both genotype and lifestyle factors. Appropriate study design (sample size) is crucial in avoiding false positives and ensuring that studies have enough power to detect significant interactions, the ideal design being a nested case-control study within a cohort. A growing number of studies are examining the influence of gene-environmental interactions on obesity in either epidemiological observational or intervention studies. Positive evidence has been obtained for genes involved in adiposity, lipid metabolism or energy regulation such as PPARgamma2 (Pro12Ala), beta-adrenoceptor 2 (Gln27Glu) or uncoupling proteins 1, 2 and 3. Variants on other genes relating to appetite regulation such as melanocortin and leptin receptors have also been investigated. Examples of some recently-identified interactions are discussed.

Nut Consumption and Weight Gain in a Mediterranean Cohort: The SUN Study

Objective: To assess the association, in a Mediterranean population, between nut consumption and risk of weight gain (at least 5 kg) or the risk of becoming overweight/obese.

Presence of leptin receptors in rat small intestine and leptin effect on sugar absorption

Leptin is involved in food intake and thermogenesis regulation. Since leptin receptor expression has been found in several tissues including small intestine, a possible role of leptin in sugar absorption by the intestine was investigated. Leptin inhibited d‐galactose uptake by rat small intestinal rings 33% after 5 min of incubation. The inhibition increased to 56% after 30 min. However, neither at 5 min nor at 30 min did leptin prevent intracellular galactose accumulation. This leptin effect was accompanied by a decrease of the active sugar transport apparent V max (20 vs. 4.8 μmol/g wet weight 5 min) and apparent K m (15.8 vs. 5.3 mM) without any change in the phlorizin‐resistant component. On the other hand, immunohistochemical experiments using anti‐leptin monoclonal antibodies recognized leptin receptors in the plasma membrane of immune cells located in the lamina propria. These results indicate for the first time that leptin has a rapid inhibitory effect on sugar absorption and demonstrate the presence of leptin receptors in the intestinal mucosa.

Effects of Weight Loss and Long-Term Weight Maintenance With Diets Varying in Protein and Glycemic Index on Cardiovascular Risk Factors The Diet, Obesity, and Genes (DiOGenes) Study: A Randomized, Controlled Trial

Background— We sought to separately examine the effects of either weight loss or diets varying in protein content and glycemic index without further changes in body weight on cardiovascular risk factors within the Diet, Obesity, and Genes study (DiOGenes). Methods and Results— DiOGenes is a pan-European controlled dietary intervention study in 932 overweight adults who first lost body weight on an 8-week low-calorie diet and were then randomized to 1 of 5 ad libitum diets for 26 weeks. The diets were either high or low protein or high or low glycemic index in 4 combinations or control. Weight loss (−11.23 kg; 95% confidence interval, −11.54 to −10.92; P<0.001) reduced high-sensitivity C-reactive protein (−1.15 mg/L; 95% confidence interval, −1.30 to −0.41; P<0.001), low- and high-density lipoprotein cholesterol, triglycerides, and blood pressure. During the 26-week weight maintenance period in the intention-to-treat analysis, the further decrease of high-sensitivity C-reactive protein blood levels was −0.46 mg/L greater (95% confidence interval, −0.79 to −0.13) in the groups assigned to low-glycemic-index diets than in those on high-glycemic-index diets (P<0.001). Groups on low-protein diets achieved a −0.25 mg/L greater reduction in high-sensitivity C-reactive protein (95% confidence interval, −0.59 to −0.17) than those on high-protein diets (P<0.001), whereas lipid profiles and blood pressure were not differently affected. Conclusions— This large-scale intervention study clearly separates weight loss from dietary composition–related effects. Low-glycemic-index carbohydrates and, to a lesser extent, low-protein intake may specifically reduce low-grade inflammation and associated comorbidities in overweight/obese adults. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT00390637.