The Outcome of Metabolic and Bariatric Surgery in Morbidly Obese Patients with Different Genetic Variants Associated with Obesity: A Systematic Review.

Metabolic and bariatric surgery (MBS) effectively treats obesity and related comorbidities, though individual responses vary. This systematic review examines how genetic variants influence MBS outcomes in morbidly obese patients. A comprehensive search in PubMed, Embase, Medline, and the Cochrane Library identified 1572 studies, with 52 meeting the inclusion criteria. Two reviewers independently filtered and selected studies, including relevant cross-references. Research focused on polymorphisms in genes such as UCP2, UCP3, 5-HT2C, MC4R, FKBP5, FTO, CAT haplotypes, LYPAL-1, PTEN, FABP-2, CNR1, LEP656, LEP223, GLP-1R, APOA-1, APOE, ADIPOQ, IL-6, PGC1a, TM6SF2, MBOAT7, PNPLA3, TCF7L2, ESR1, GHSR, GHRL, CD40L, DIO2, ACSL5, CG, TAS2R38, CD36, OBPIIa, NPY, BDNF, CLOCK, and CAMKK2. Most studies explored associations with post-surgery weight loss, while some examined metabolic, cardiovascular, taste, and eating behavior effects as well. Understanding the role of genetic factors in weight loss and metabolic outcomes post-MBS can help tailor personalized treatment plans for improved efficacy and long-term success. Further research with larger sample sizes and extended follow-up is needed to clarify the effects of many genetic variants on MBS outcomes in morbidly obese patients.

Survey on Interaction Between Nutrient Status and Selected Polymorphisms in Association with Weight Loss of Patients with Severe Obesity Underwent Bariatric Surgery.

BACKGROUND: There is little information about the effect of single nucleotide polymorphisms (SNP) and nutritional status and weight loss after bariatric surgery. This study investigated the interactive effect of eight obesity-related SNPs and nutritional status on weight loss after Roux-en-Y gastric bypass (RYGB). METHOD: This is a case-control study. After 1-year follow-up, the patients who underwent RYGB were dividing into two groups. The case group consisted of patients who lost more than 50% of their excess body weight (EBW%) 1 year after the surgery. The control group included patients who lost < 50% of EBW at same time frame. Then, the relationship between eight SNPs related to UCP2, FTO, LEPR, GHRL, and NPY genes with weight loss were checked. RESULTS: In this study, 160 patients were recruited. The median of age for case and control group were 43 and 42 respectively. The presence of mutant variant NPYrs16147 had a significant relationship in terms of weight loss between the two groups (P > 0.05). In dominant model, two SNPs, UCP2 rs659366 and UCP2 rs660339, showed protective effect of the vitamin D deficiency. CONCLUSION: In conclusion, the presence mutant variant of NPYrs16147 is directly related to the incidence of weight loss greater than 50% of EBW. However, it is apparent individual behavioral, dietary, and other factors may have more influence on weight loss among patients underwent RYGB.

Are weight loss and metabolic outcomes of bariatric surgery influenced by candidate glucocorticoid receptor gene polymorphisms? A prospective study.

BACKGROUND: Bariatric surgery is the most effective treatment for severe obesity. There can be variation in the degree of weight reduction following bariatric surgery. It is unknown whether single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor locus (GRL) affect postoperative weight loss and metabolic outcomes. MATERIALS/METHODS: We studied the association between selected candidate SNPs and postoperative weight loss and metabolic outcomes in patients with severe obesity undergoing bariatric surgery. The polymorphisms rs41423247 (Bcl1), rs56149945 (N363S) and rs6189/rs6190 (ER22/23EK) were analysed. RESULTS: The 139 participants included 95 women (68.3%) and had a median (interquartile range) age of 53.0 (46.0-60.0) years and mean (SD) weight of 140.8 (28.8) kg and body mass index of 50.3 (8.6) kg/m2. At baseline, 59 patients had type 2 diabetes (T2D), 60 had hypertension and 35 had obstructive sleep apnoea syndrome treated with continuous positive airway pressure (CPAP). 84 patients (60.4%) underwent gastric bypass and 55 (39.6%) underwent sleeve gastrectomy. There were no significant differences in weight loss, glycated haemoglobin (HbA1c) or lipid profile categorized by genotype status, sex or median age. There was significant weight reduction after bariatric surgery with a postoperative BMI of 34.1 (6.8) kg/m2 at 24 months (p < 0.001). CONCLUSION: While GRL polymorphisms with a known deleterious effect on adipose tissue mass and function may have a small, additive effect on the prevalence of obesity and related metabolic disorders in the population, we suggest that the relatively weak biological influence of these SNPs is readily overcome by bariatric surgery.

Impact of the rs822393 Variant on Adiponectin Levels and Metabolic Parameters after Weight Loss Secondary to a High-Fat Hypocaloric Diet with Mediterranean Pattern.

INTRODUCTION: The effects of the rs822393 variant of ADIPOQ gene on metabolic parameters such as insulin resistance and adiponectin levels following weight loss through dietary intervention are still uncertain. The aim of this study was to evaluate the role of rs822393 of ADIPOQ gene on adiponectin levels and metabolic parameters after weight loss with a high-fat hypocaloric diet with Mediterranean pattern during 12 weeks. METHODS: A population of 283 patients with obesity was allocated to a dietary intervention trial with a high-fat hypocaloric diet during 12 weeks. Adiposity and biochemical parameters were determined. rs822393 was assessed with a dominant model analysis (CC vs. CT + TT). RESULTS: These patients had three different genotypes: CC (59.0%), CT (33.6%), and TT (7.4%). The allelic frequencies for C and T were 0.89 and 0.20, respectively. Basal and post-intervention HDL cholesterol, adiponectin levels, and adiponectin/leptin ratio were lower in T-allele than non-T-allele carriers. After dietary intervention, BMI, weight, fat mass, waist circumference, systolic blood pressure, insulin, HOMA-IR, leptin, total cholesterol, and LDL cholesterol levels improved significantly in both genotype groups. Moreover, HDL cholesterol (CC vs. CT + TT) (delta: 8.9 ± 1.1 mg/dL vs. 1.7 ± 0.8 mg/dL; p = 0.02), serum adiponectin in non-T-allele carriers (43.1 ± 5.9 ng/dL vs. 2.8 ± 3 0.0 ng/dL; p = 0.01), and adiponectin/leptin ratio (1.37 ± 0.1 units vs. 0.17 ± 0.08 units; p = 0.02) improved only in non-T-allele carriers after weight loss. CONCLUSION: Individuals with obesity and without the T allele of rs822393 experienced improvements in adiponectin levels, adiponectin/leptin ratio, and HDL cholesterol levels after following a high-fat hypocaloric diet with a Mediterranean pattern.

Mutations in the leptin-melanocortin pathway and weight loss after bariatric surgery: a systematic review and meta-analysis.

OBJECTIVE: The objective of this meta-analysis was to quantify the overall effects of gene mutations in the leptin-melanocortin pathway on short- and long-term weight loss after bariatric surgery. METHODS: MEDLINE, PubMed, and Embase were searched, and data were analyzed using ReviewManager (RevMan) version 5.4. The datasets were divided into two subgroups based on postoperative time, and the outcome measure was the percentage of total weight loss. Meta-regression analysis was performed, and the outcome was presented as the weighed mean difference of percentage of total weight loss. RESULTS: The results showed that patients with mutations in the leptin-melanocortin pathway experienced 3.03% lower total weight loss after bariatric surgery (mean difference, -3.03; 95% CI: -3.63 to -2.44), mainly reflected in lower long-term postoperative weight loss (mean difference, -3.43; 95% CI: -4.09 to -2.77), whereas mutation carriers exhibited a magnitude of short-term postoperative weight loss that was similar to patients without such mutations (total difference value, -1.13; 95% CI: -2.57 to 0.31). CONCLUSIONS: Mutations in leptin-melanocortin pathway genes reduce long-term weight loss after bariatric surgery, whereas this effect may not be reflected during the period of rapid weight loss within 12 months. These genetic variants increase the difficulties in maintaining patients' long-term weight loss.

Interaction Effects of FTO and MC4R Polymorphisms on Total Body Weight Loss, Post-Surgery Weight, and Post-Body Mass Index after Bariatric Surgery.

Bariatric surgery (BS) is considered the most effective intervention for patients with severe obesity and is used to maintain long-term weight loss and glycemic control. The aim of this study was to analyze the effects of genotypes and haplotypes of the fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes on total body weight loss (TBWL), post-surgery weight, and post-BMI after bariatric surgery. We retrospectively selected 101 patients from Bajio High Specialty Regional Hospital, León Guanajuato, México, who underwent Roux-en-Y gastric bypass (RYGB) to determine their body mass index (BMI), blood pressure, biochemical characteristics, and comorbidities. Post-surgery, patients were referred for registered anthropometry and blood pressure. Glucose, lipid and hepatic profiles, and insulin, leptin, and ghrelin levels were measured, and rs9939609, rs9930506, and rs1421085 FTO and rs17782313 MC4R polymorphisms were genotyped. Six (4-8) years after BS, post-surgery weight was greater in carriers of the rs9939609 and rs1421085 risk genotypes. TBWL was lower for the rs9930506 and rs1421085 risk genotypes. Insulin and HOMA-IR were greater in patients with the three FTO polymorphisms. There were significant interaction effects of the rs9930506 and rs1421085 FTO risk genotypes on weight and BMI in response to BS. No association was found with the MC4R polymorphism. The genotypes and haplotypes of the FTO gene influence post-surgery weight, TBWL, insulin levels, and HOMA-IR.

Efficacy of a Comprehensive Weight Reduction Intervention in Male Adolescents With Different FTO Genotypes.

BACKGROUND: The FTO gene polymorphisms may influence the effects of lifestyle interventions on obesity. The present study aimed to assess the influence of the rs9930506 FTO gene polymorphism on the success of a comprehensive weight loss intervention in male adolescents with overweight and obesity. METHODS: This study was carried out on 96 adolescent boys with overweight and obesity who were randomly assigned to the intervention (n = 53) and control (n = 43) groups. The blood samples of the participants were collected, and the FTO gene was genotyped for the rs9930506 polymorphism. A comprehensive lifestyle intervention including changes in diet and physical activity was performed for 8 weeks in the intervention group. RESULTS: Following the lifestyle intervention, BMI and fat mass decreased significantly in the intervention group compared with the control group (both p < 0.05), while no change was found in weight, height or body muscle percentage between the groups. The participants in the intervention group with the AA/AG genotype and not in carriers of the GG genotype had a significantly higher reduction in BMI (-1.21 vs. 1.87 kg/m2, F = 4.07, p < 0.05) compared with the control group. CONCLUSION: The intervention in individuals with the AA/AG genotype has been significantly effective in weight loss compared with the control group. The intervention had no association effect on anthropometric indices in adolescents with the GG genotype of the FTO rs9930506 polymorphism. TRIAL REGISTRATION: Name of the registry: National Nutrition and Food Technology Research Institute; Trial registration number: IRCT2016020925699N2; Date of registration: 24/04/2016; URL of trial registry record: https://www.irct.ir/trial/21447.

Genetics of Exercise and Diet-Induced Fat Loss Efficiency: A Systematic Review.

Physical exercise and dieting are well-known and effective methods for fat loss and improving cardiovascular health. However, different individuals often react differently to the same exercise regimen or dietary plan. While specific individuals may undergo substantial fat loss, others may observe only limited effects. A wide range of inter-individual variability in weight gain and changes in body composition induced by physical exercises and diets led to an investigation into the genetic factors that may contribute to the individual variations in such responses. This systematic review aimed at identifying the genetic markers associated with fat loss resulting from diet or exercise. A search of the current literature was performed using the PubMed database. Forty-seven articles met the inclusion criteria when assessing genetic markers associated with weight loss efficiency in response to different types of exercises and diets. Overall, we identified 30 genetic markers of fat-loss efficiency in response to different kinds of diets and 24 in response to exercise. Most studies (n = 46) used the candidate gene approach. We should aspire to the customized selection of exercise and dietary plans for each individual to prevent and treat obesity.

Association between variants in TCF7L2, CTRB1/2, and GLP-1R genes and response to therapy with glucagon-like peptide-1 receptor agonists.

OBJECTIVES: The factors determining the response to treatment with glucagon-like peptide-1 receptor agonists (GLP-1- RAs) have not been clarified. The present study investigated the association between polymorphisms in TCF7L2, CTRB1/2, and GLP-1 R genes and response to GLP-1 RAs regarding glycemic control and weight loss among Greek patients with type 2 diabetes mellitus (T2DM). METHODS: Patients (n = 191) treated with GLP-1 RAs for at least 6 months were included. Participants were genotyped for TCF7L2 rs7903146 (C>T), CTRB1/2 rs7202877 (T>G) and GLP-1 R rs367543060 (C>T) polymorphisms. Clinical and laboratory parameters were measured before, 3, and 6 months after treatment initiation. The patients were classified into responders and non-responders according to specific criteria. RESULTS: Carriers of at least one rs7903146 'T' allele and rs7202877 'G' allele presented similar glucose control and weight loss response to GLP-1 RAs with the respective homozygous wild-type genotypes [odds ratio (OR): 1.08, 95% confidence interval (CI): 0.5, 2.31, p = 0.85 and OR: 1.35, 95% CI: 0.66, 2.76, p = 0.42; OR: 1.4, 95% CI: 0.56, 3.47, p = 0.47 and OR: 1.28, 95% CI: 0.55, 2.98, p = 0.57, respectively]. Regarding the GLP-1 R polymorphism, all participants were homozygous for the wild-type allele; thus, no comparisons were feasible. Female sex (p = 0.03) and lower baseline weight (p = 0.024) were associated with an improved glycemic and weight loss response, respectively. CONCLUSION: There is no evidence suggesting a role for the variants studied in response to GLP-1 RA therapy in people with T2DM. However, specific demographic and clinical factors may be related to a better response to treatment with these agents.

The Impact of Glucomannan, Inulin, and Psyllium Supplementation (SolowaysTM) on Weight Loss in Adults with FTO, LEP, LEPR, and MC4R Polymorphisms: A Randomized, Double-Blind, Placebo-Controlled Trial.

This study aimed to determine the impact of a fiber supplement on body weight and composition in individuals with obesity with specific genetic polymorphisms. It involved 112 adults with obesity, each with at least one minor allele in the FTO, LEP, LEPR, or MC4R polymorphism. Participants were randomized to receive either a fiber supplement (glucomannan, inulin, and psyllium) or a placebo for 180 days. The experimental group showed significant reductions in body weight (treatment difference: -4.9%; 95% CI: -6.9% to -2.9%; p < 0.01) and BMI (treatment difference: -1.4 kg/m2; 95% CI: -1.7 to -1.2; p < 0.01) compared to placebo. Further significant decreases in fat mass (treatment difference: -13.0%; 95% CI: -14.4 to -11.7; p < 0.01) and visceral fat rating (treatment difference: -1.3; 95% CI: -1.6 to -1.0; p < 0.01) were noted. Homozygous minor allele carriers experienced greater decreases in body weight (treatment difference: -3.2%; 95% CI: -4.9% to -1.6%; p < 0.01) and BMI (treatment difference: -1.2 kg/m2; 95% CI: -2.0 to -0.4; p < 0.01) compared to heterozygous allele carriers. These carriers also had a more significant reduction in fat mass (treatment difference: -9.8%; 95% CI: -10.6 to -9.1; p < 0.01) and visceral fat rating (treatment difference: -0.9; 95% CI: -1.3 to -0.5; p < 0.01). A high incidence of gastrointestinal events was reported in the experimental group (74.6%), unlike the placebo group, which reported no side effects. Dietary supplementation with glucomannan, inulin, and psyllium effectively promotes weight loss and improves body composition in individuals with obesity, particularly those with specific genetic polymorphisms.

Analysis of 16s rRNA Gene Sequencing in Feces: The Impact of Bariatric Surgery on the Gut Microbiota in Patients with Obesity.

PURPOSE: Obesity is a risk factor for many chronic diseases. This study aimed to investigate the effect of bariatric surgery on the gut microbiota from patients with obesity. MATERIALS AND METHODS: The microbiota composition from stool samples before and after bariatric surgery were identified using bacterial 16S rRNA gene sequencing. Based on the speed of weight loss, patients were classified as the slow-loss group and fast-loss group. The ɑ- and ß-diversity analysis was done to compare the species richness, evenness, and overall structure of the microbiota between different groups. Next, linear discriminant analysis effect size (LEfSe) and receiver operating characteristic (ROC) analysis were implemented to identify high-dimensional biomarkers and significantly different species of microbial taxa between different groups. Finally, the pathway analysis was inferred using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to predict the functional profiling of microbial communities. RESULTS: ß-diversity analysis suggested that species diversity of preoperative samples of slow-loss group was significantly higher than the fast-loss group. High levels of Oscillospira and Abiotrophia in the preoperative gut microbiota may lead to poor postoperative weight loss. For patients with poor postoperative weight loss due to changes in gut microbiota, the gut microbiota is mainly composed of Lactobacillus. For patients with good postoperative results, the gut microbiota is mainly composed of Escherichia, Robinsonella, and Dialister. In addition, multiple metabolic-related pathways were significantly different between the four groups. CONCLUSION: This comparative study revealed biomarker species based on microfloral composition in patients with obesity before and after bariatric surgery.

Impact of polygenic score for BMI on weight loss effectiveness and genome-wide association analysis.

BACKGROUND: While environmental factors play an important role in weight loss effectiveness, genetics may also influence its success. We examined whether a genome-wide polygenic score for BMI was associated with weight loss effectiveness and aimed to identify common genetic variants associated with weight loss. METHODS: Participants in the ONTIME study (n = 1210) followed a uniform, multimodal behavioral weight-loss intervention. We first tested associations between a genome-wide polygenic score for higher BMI and weight loss effectiveness (total weight loss, rate of weight loss, and attrition). We then conducted a genome-wide association study (GWAS) for weight loss in the ONTIME study and performed the largest weight loss meta-analysis with earlier studies (n = 3056). Lastly, we ran exploratory GWAS in the ONTIME study for other weight loss outcomes and related factors. RESULTS: We found that each standard deviation increment in the polygenic score was associated with a decrease in the rate of weight loss (Beta (95% CI) = -0.04 kg per week (-0.06, -0.01); P = 3.7 × 10-03) and with higher attrition after adjusting by treatment duration. No associations reached genome-wide significance in meta-analysis with previous GWAS studies for weight loss. However, associations in the ONTIME study showed effects consistent with published studies for rs545936 (MIR486/NKX6.3/ANK1), a previously noted weight loss locus. In the meta-analysis, each copy of the minor A allele was associated with 0.12 (0.03) kg/m2 higher BMI at week five of treatment (P = 3.9 × 10-06). In the ONTIME study, we also identified two genome-wide significant (P < 5×10-08) loci for the rate of weight loss near genes implicated in lipolysis, body weight, and metabolic regulation: rs146905606 near NFIP1/SPRY4/FGF1; and rs151313458 near LSAMP. CONCLUSION: Our findings are expected to help in developing personalized weight loss approaches based on genetics. CLINICAL TRIAL REGISTRATION: Obesity, Nutrigenetics, Timing, and Mediterranean (ONTIME; clinicaltrials.gov: NCT02829619) study.

Transcriptional and epigenetic changes after dietary and surgical weight loss interventions in an animal model of obesity.

BACKGROUND: Identifying determinants that can predict response to weight loss interventions is imperative for optimizing therapeutic benefit. We aimed to identify changes in DNA methylation and mRNA expression of a subset of target genes following dietary and surgical interventions in high-fat-diet (HFD)-induced obese rats. METHODS: Forty-two adult Wistar Han male rats were divided into two groups: control rats (n = 7) and obese rats (n = 28), fed a HFD for 10 weeks (t10). Obese rats were randomly subdivided into five intervention groups (seven animals per group): (i) HFD; (ii) very-low-calorie diet (VLCD); (iii) sham surgery, and (iv) sleeve gastrectomy (SG). At week sixteen (t16), animals were sacrificed and tissue samples were collected to analyze changes in DNA methylation and mRNA expression of the selected genes. RESULTS: By type of intervention, the surgical procedures led to the greatest weight loss. Changes in methylation and/or expression of candidate genes occurred proportionally to the effectiveness of the weight loss interventions. Leptin expression, increased sixfold in the visceral fat of the obese rats, was partially normalized after all interventions. The expression of fatty acid synthase (FASN) and monocyte chemoattractant protein 1 (MCP-1) genes, which was reduced 0.5- and 0.15-fold, respectively, in the liver tissue of obese rats, were completely normalized after weight loss interventions, particularly after surgical interventions. The upregulation of FASN and MCP-1 gene expression was accompanied by a significant reduction in promoter methylation, up to 0.5-fold decrease in the case of the FASN (all intervention groups) and a 0.8-fold decrease in the case of the MCP-1 (SG group). CONCLUSIONS: Changes in tissue expression of specific genes involved in the pathophysiological mechanisms of obesity can be significantly attenuated following weight loss interventions, particularly surgery. Some of these genes are regulated by epigenetic mechanisms.

Novel markers and networks related to restored skeletal muscle transcriptome after bariatric surgery.

OBJECTIVE: The aim of this study was to discover novel markers underlying the improvement of skeletal muscle metabolism after bariatric surgery. METHODS: Skeletal muscle transcriptome data of lean people and people with obesity, before and 1 year after bariatric surgery, were subjected to weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression. Results of LASSO were confirmed in a replication cohort. RESULTS: The expression levels of 440 genes differing between individuals with and without obesity were no longer different 1 year after surgery, indicating restoration. WGCNA clustered 116 genes with normalized expression in one major module, particularly correlating to weight loss and decreased plasma free fatty acids (FFA), 44 of which showed an obesity-related phenotype upon deletion in mice. Among the genes of the major module, 105 represented prominent markers for reduced FFA concentration, including 55 marker genes for decreased BMI in both the discovery and replication cohorts. CONCLUSIONS: Previously unknown gene networks and marker genes underlined the important role of FFA in restoring muscle gene expression after bariatric surgery and further suggest novel therapeutic targets for obesity.

Under pressure-exploring partner changes, physiological responses and telomere dynamics in northern gannets across varying breeding conditions.

Background: Life history theory predicts trade-offs between reproduction and survival in species like the northern gannet (Morus bassanus). During breeding, demanding foraging conditions lead them to expand their foraging range and diversify their diet, increasing the risk of reproductive failure. Changing partners may enhance breeding success but lead to more physiological costs. Methods: To investigate the physiological costs of reproduction upon partner changes, we measured and compared 21 biomarkers related to telomere dynamics, oxidative stress, inflammation, hematology, nutritional status, and muscle damage. We used a longitudinal approach with gannets (n = 38) over three contrasting years (2017, 2018 and 2019). Results: Our results suggest that annual breeding conditions exert a greater influence on physiological changes than partnership status. Individuals that changed partner experienced greater short-term stress than retained partners. This transient increase in stress was marked by short-term increases in oxidative lipid damage, lower antioxidant capacity, signs of inflammation, and greater weight loss than individuals that retained partners. During favorable conditions, individuals that changed mates had stabilized telomere length, decreased antioxidant capacity, glucose concentration, and muscle damage, along with increased oxygen transport capacity. Conversely, unfavorable breeding conditions led to increased telomere attrition, stabilized antioxidant capacity, decreased inflammation susceptibility, diminished oxygen transport capacity, and increased muscle damage. In the cases where partners were retained, distinct physiological changes were observed depending on the year's conditions, yet the telomere dynamics remained consistent across both partnership status categories. During the favorable year, there was an increase in unsaturated fatty acids and oxygen transport capacity in the blood, coupled with a reduction in inflammation potential and protein catabolism. In contrast, during the unfavorable year in the retained mates, we observed an increase in oxidative DNA damage, antioxidant capacity, weight loss, but a decrease in inflammation susceptibility as observed in changed mates. Discussion: Our study shows that behavioral flexibility such as mate switching can help seabirds cope with the challenges of food scarcity during reproduction, but these coping strategies may have a negative impact on physiological status at the individual level. In addition, the marked reduction in telomere length observed during harsh conditions, coupled with the stabilization of telomere length in favorable conditions, highlights the long-term physiological impact of annual breeding conditions on seabirds. These findings underscore the effect on their potential survival and fitness, emphasizing that the influence of annual breeding conditions is greater than that of partnership status.

CETP and APOA2 polymorphisms are associated with weight loss and healthy eating behavior changes in response to digital lifestyle modifications.

Response to digital healthcare lifestyle modifications is highly divergent. This study aimed to examine the association between single nucleotide polymorphism (SNP) genotypes and clinical efficacy of a digital healthcare lifestyle modification. We genotyped 97 obesity-related SNPs from 45 participants aged 18-39 years, who underwent lifestyle modification via digital cognitive behavioral therapy for obesity for 8 weeks. Anthropometric, eating behavior phenotypes, and psychological measures were analyzed before and after the intervention to identify their clinical efficacy. CETP (rs9939224) SNP significantly predict "super-responders" with greater body mass index (BMI) reduction (p = 0.028; GG - 2.91%, GT - 9.94%), while APOA2 (rs5082) appeared to have some potential for predicting "poor-responders" with lower BMI reduction (p = 0.005; AA - 6.17%, AG + 2.05%, and GG + 5.11%). These SNPs was also associated with significant differences in eating behavior changes, healthy diet proportions, health diet diversity, emotional and restrained eating behavior changes. Furthermore, classification using gene-gene interactions between rs9939224 and rs5082 significantly predicted the best response, with a greater decrease in BMI (p = 0.038; - 11.45% for the best response group (CEPT GT/TT × APOA2 AA) vs. + 2.62% for the worst response group (CEPT GG × APOA2 AG/GG)). CETP and APOA2 SNPs can be used as candidate markers to predict the efficacy of digital healthcare lifestyle modifications based on genotype-based precision medicine.Trial registration: NCT03465306, ClinicalTrials.gov. Registered March, 2018.

A Predictive Tool Based on DNA Methylation Data for Personalized Weight Loss through Different Dietary Strategies: A Pilot Study.

BACKGROUND AND AIMS: Obesity is a public health problem. The usual treatment is a reduction in calorie intake and an increase in energy expenditure, but not all individuals respond equally to these treatments. Epigenetics could be a factor that contributes to this heterogeneity. The aim of this research was to determine the association between DNA methylation at baseline and the percentage of BMI loss (%BMIL) after two dietary interventions, in order to design a prediction model to evaluate %BMIL based on methylation data. METHODS AND RESULTS: Spanish participants with overweight or obesity (n = 306) were randomly assigned to two lifestyle interventions with hypocaloric diets: one moderately high in protein (MHP) and the other low in fat (LF) for 4 months (Obekit study; ClinicalTrials.gov ID: NCT02737267). Basal DNA methylation was analyzed in white blood cells using the Infinium MethylationEPIC array. After identifying those methylation sites associated with %BMIL (p < 0.05 and SD > 0.1), two weighted methylation sub-scores were constructed for each diet: 15 CpGs were used for the MHP diet and 11 CpGs for the LF diet. Afterwards, a total methylation score was made by subtracting the previous sub-scores. These data were used to design a prediction model for %BMIL through a linear mixed effect model with the interaction between diet and total score. CONCLUSION: Overall, DNA methylation predicts the %BMIL of two 4-month hypocaloric diets and was able to determine which type of diet is the most appropriate for each individual. The results of this pioneer study confirm that epigenetic biomarkers may be further used for precision nutrition and the design of personalized dietary strategies against obesity.

RS2289487 variation in PERILIPIN gene is a predictor of weight loss and protection against impaired glucose metabolism after a meal-replacement diet in postmenopausal obese females.

OBJECTIVE: The PERILIPIN1 (PLIN1) gene encodes an adipocyte-associated protein that modulates weight. The objective was to evaluate the role of the rs2289487 genetic variant of the PLIN1 gene on weight loss and glucose metabolism secondary to a partial meal replacement (pMR) hypocaloric diet. PATIENTS AND METHODS: We conducted an interventional study in 111 postmenopausal obese females with body mass index (BMI) > 35 kg/m2. The subjects received two intakes per day of a normocaloric hyperproteic formula for 12 weeks. RESULTS: After the pMR diet, body weight, (BMI), fat mass, waist circumference, fasting insulin levels and HOMA-IR decreased in both genotype groups. The improvements in these parameters were higher in C allele carriers than in subjects with TT genotype. The percentage of patients who achieved 7.5% weight loss was higher in the C carriers (57.4% vs. 27.6%), (adjusted Odds Ratio 2.14, 95% CI = 1.33-9.40; p = 0.02). The decrease in the percentage of diabetes mellitus or impaired fasting glucose decrease was statistically significant in C allele carriers (30.2% vs. 18.9%; p = 0.01) (OR 0.54, 95% CI = 0.22-0.78; p = 0.02). CONCLUSIONS: The C allele of rs2289487 predicts the magnitude of weight loss resulting from a pMR diet. These adiposity improvements produce a better improvement in insulin resistance and the percentage of impaired glucose metabolism.

The Personalized Nutrition Study (POINTS): evaluation of a genetically informed weight loss approach, a Randomized Clinical Trial.

Weight loss (WL) differences between isocaloric high-carbohydrate and high-fat diets are generally small; however, individual WL varies within diet groups. Genotype patterns may modify diet effects, with carbohydrate-responsive genotypes losing more weight on high-carbohydrate diets (and vice versa for fat-responsive genotypes). We investigated whether 12-week WL (kg, primary outcome) differs between genotype-concordant and genotype-discordant diets. In this 12-week single-center WL trial, 145 participants with overweight/obesity were identified a priori as fat-responders or carbohydrate-responders based on their combined genotypes at ten genetic variants and randomized to a high-fat (n = 73) or high-carbohydrate diet (n = 72), yielding 4 groups: (1) fat-responders receiving high-fat diet, (2) fat-responders receiving high-carbohydrate diet, (3) carbohydrate-responders receiving high-fat diet, (4) carbohydrate-responders receiving high-carbohydrate diet. Dietitians delivered the WL intervention via 12 weekly diet-specific small group sessions. Outcome assessors were blind to diet assignment and genotype patterns. We included 122 participants (54.4 [SD:13.2] years, BMI 34.9 [SD:5.1] kg/m2, 84% women) in the analyses. Twelve-week WL did not differ between the genotype-concordant (-5.3 kg [SD:1.0]) and genotype-discordant diets (-4.8 kg [SD:1.1]; adjusted difference: -0.6 kg [95% CI: -2.1,0.9], p = 0.50). With the current ability to genotype participants as fat- or carbohydrate-responders, evidence does not support greater WL on genotype-concordant diets. ClinicalTrials identifier: NCT04145466.