Sex-Specific Associations between Gut Prevotellaceae and Host Genetics on Adiposity

The gut microbiome has been recognized as a tool for understanding adiposity accumulation and for providing personalized nutrition advice for the management of obesity and accompanying metabolic complications. The genetic background is also involved in human energy homeostasis. In order to increase the value of nutrigenetic dietary advice, the interplay between genetics and microbiota must be investigated. The purpose of the present study was to evaluate interactive associations between gut microbiota composition and 95 obesity-related single nucleotide polymorphisms (SNPs) searched in the literature. Oral mucosa and fecal samples from 360 normal weight, overweight and obese subjects were collected. Next generation genotyping of these 95 SNPs and fecal 16S rRNA sequencing were performed. A genetic risk score (GRS) was constructed with 10 SNPs statistically or marginally associated with body mass index (BMI). Several microbiome statistical analyses at family taxonomic level were applied (LEfSe, Canonical Correspondence Analysis, MetagenomeSeq and Random Forest), and Prevotellaceae family was found in all of them as one of the most important bacterial families associated with BMI and GRS. Thus, in this family it was further analyzed the interactive association between BMI and GRS with linear regression models. Interestingly, women with higher abundance of Prevotellaceae and higher GRS were more obese, compared to women with higher GRS and lower abundance of Prevotellaceae. These findings suggest relevant interrelationships between Prevotellaceae and the genetic background that may determine interindividual BMI differences in women, which opens the way to new precision nutrition-based treatments for obesity.

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Modeling of an integrative prototype based on genetic, phenotypic, and environmental information for personalized prescription of energy-restricted diets in overweight/obese subjects

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz286 ◽

2019 ◽

Vol 111 (2) ◽

pp. 459-470 ◽

Cited By ~ 6

Author(s):

Omar Ramos-Lopez ◽

Marta Cuervo ◽

Leticia Goni ◽

Fermin I Milagro ◽

Jose I Riezu-Boj ◽

...

Keyword(s):

Energy Homeostasis ◽

Holistic Approach ◽

Environmental Information ◽

Energy Restriction ◽

Risk Scores ◽

Dietary Advice ◽

Nucleotide Polymorphisms ◽

Linear Regression Models ◽

Decision Algorithm ◽

Macronutrient Distribution

ABSTRACT Background Interindividual variability in weight loss and metabolic responses depends upon interactions between genetic, phenotypic, and environmental factors. Objective We aimed to model an integrative (nutri) prototype based on genetic, phenotypic, and environmental information for the personalized prescription of energy-restricted diets with different macronutrient distribution. Methods A 4-mo nutritional intervention was conducted in 305 overweight/obese volunteers involving 2 energy-restricted diets (30% restriction) with different macronutrient distribution: a moderately high-protein (MHP) diet (30% proteins, 30% lipids, and 40% carbohydrates) and a low-fat (LF) diet (22% lipids, 18% proteins, and 60% carbohydrates). A total of 201 subjects with good dietary adherence were genotyped for 95 single nucleotide polymorphisms (SNPs) related to energy homeostasis. Genotyping was performed by targeted next-generation sequencing. Two weighted genetic risk scores for the MHP (wGRS1) and LF (wGRS2) diets were computed using statistically relevant SNPs. Multiple linear regression models were performed to estimate percentage BMI decrease depending on the dietary macronutrient composition. Results After energy restriction, both the MHP and LF diets induced similar significant decreases in adiposity, body composition, and blood pressure, and improved the lipid profile. Furthermore, statistically relevant differences in anthropometric and biochemical markers depending on sex and age were found. BMI decrease in the MHP diet was best predicted at ∼28% (optimism-corrected adjusted R2 = 0.279) by wGRS1 and age, whereas wGRS2 and baseline energy intake explained ∼29% (optimism-corrected adjusted R2 = 0.287) of BMI decrease variability in the LF diet. The incorporation of these predictive models into a decision algorithm allowed the personalized prescription of the MHP and LF diets. Conclusions Different genetic, phenotypic, and exogenous factors predict BMI decreases depending on the administration of a hypocaloric MHP diet or an LF diet. This holistic approach may help to personalize dietary advice for the management of excessive body weight using precision nutrition variables. This trial was registered at clinicaltrials.gov as NCT02737267.

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Interplay of an Obesity-Based Genetic Risk Score with Dietary and Endocrine Factors on Insulin Resistance

Nutrients ◽

10.3390/nu12010033 ◽

2019 ◽

Vol 12 (1) ◽

pp. 33 ◽

Cited By ~ 2

Author(s):

Omar Ramos-Lopez ◽

José Ignacio Riezu-Boj ◽

Fermin I. Milagro ◽

Marta Cuervo ◽

Leticia Goni ◽

...

Keyword(s):

Insulin Resistance ◽

Risk Score ◽

Genetic Risk ◽

Energy Homeostasis ◽

Genetic Risk Score ◽

Resistance Index ◽

Blood Levels ◽

Model Assessment ◽

Nucleotide Polymorphisms ◽

Weighted Genetic Risk Score

This study aimed to nutrigenetically screen gene-diet and gene-metabolic interactions influencing insulin resistance (IR) phenotypes. A total of 232 obese or overweight adults were categorized by IR status: non-IR (HOMA-IR (homeostatic model assessment - insulin resistance) index ≤ 2.5) and IR (HOMA-IR index > 2.5). A weighted genetic risk score (wGRS) was constructed using 95 single nucleotide polymorphisms related to energy homeostasis, which were genotyped by a next generation sequencing system. Body composition, the metabolic profile and lifestyle variables were evaluated, where individuals with IR showed worse metabolic outcomes. Overall, 16 obesity-predisposing genetic variants were associated with IR (p < 0.10 in the multivariate model). The wGRS strongly associated with the HOMA-IR index (adj. R squared = 0.2705, p < 0.0001). Moreover, the wGRS positively interacted with dietary intake of cholesterol (P int. = 0.002), and with serum concentrations of C-reactive protein (P int. = 0.008) regarding IR status, whereas a negative interaction was found regarding adiponectin blood levels (P int. = 0.006). In conclusion, this study suggests that interactions between an adiposity-based wGRS with nutritional and metabolic/endocrine features influence IR phenotypes, which could facilitate the prescription of personalized nutrition recommendations for precision prevention and management of IR and diabetes.

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Changes in adipose tissue lipolysis gene expression and insulin sensitivity after weight loss

Endocrine Connections ◽

10.1530/ec-19-0507 ◽

2020 ◽

Vol 9 (2) ◽

pp. 90-100 ◽

Cited By ~ 1

Author(s):

Monika Karczewska-Kupczewska ◽

Agnieszka Nikołajuk ◽

Radosław Majewski ◽

Remigiusz Filarski ◽

Magdalena Stefanowicz ◽

...

Keyword(s):

Gene Expression ◽

Weight Loss ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Intervention Program ◽

Dietary Intervention ◽

Normal Weight ◽

Control Group ◽

Metabolic Complications ◽

Obese Subjects

Objective Insulin resistance is a major pathophysiological link between obesity and its metabolic complications. Weight loss (WL) is an effective tool to prevent obesity-related diseases; however, the mechanisms of an improvement in insulin sensitivity (IS) after weight-reducing interventions are not completely understood. The aim of the present study was to analyze the relationships between IS and adipose tissue (AT) expression of the genes involved in the regulation of lipolysis in obese subjects after WL. Methods Fifty-two obese subjects underwent weight-reducing dietary intervention program. The control group comprised 20 normal-weight subjects, examined at baseline only. Hyperinsulinemic-euglycemic clamp and s.c. AT biopsy with subsequent gene expression analysis were performed before and after the program. Results AT expression of genes encoding lipases (PNPLA2, LIPE and MGLL) and lipid-droplet proteins enhancing (ABHD5) and inhibiting lipolysis (PLIN1 and CIDEA) were decreased in obese individuals in comparison with normal-weight individuals. The group of 38 obese participants completed dietary intervention program and clamp studies, which resulted in a significant WL and an improvement in mean IS. However, in nine subjects from this group IS did not improve in response to WL. AT expression of PNPLA2, LIPE and PLIN1 increased only in the group without IS improvement. Conclusions Excessive lipolysis may prevent an improvement in IS during WL. The change in AT PNPLA2 and LIPE expression was a negative predictor of the change in IS after WL.

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Emotional Eating in Adolescence: Effects of Emotion Regulation, Weight Status and Negative Body Image

Nutrients ◽

10.3390/nu13010079 ◽

2020 ◽

Vol 13 (1) ◽

pp. 79

Author(s):

Lenka H. Shriver ◽

Jessica M. Dollar ◽

Susan D. Calkins ◽

Susan P. Keane ◽

Lilly Shanahan ◽

...

Keyword(s):

Body Image ◽

Emotion Regulation ◽

Emotional Regulation ◽

Emotional Eating ◽

Weight Status ◽

Normal Weight ◽

Linear Regression Models ◽

Obesity Risk ◽

Negative Body Image ◽

Increased Risk

Emotional eating is associated with an increased risk of binge eating, eating in the absence of hunger and obesity risk. While previous studies with children and adolescents suggest that emotion regulation may be a key predictor of this dysregulated eating behavior, little is known about what other factors may be influencing the link between emotional regulation and emotional eating in adolescence. This multi-method longitudinal study (n = 138) utilized linear regression models to examine associations between childhood emotion regulation, adolescent weight status and negative body image, and emotional eating at age 17. Emotion regulation predicted adolescent emotional eating and this link was moderated by weight status (β = 1.19, p < 0.01) and negative body image (β = −0.34, p < 0.01). Higher engagement in emotional eating was predicted by lower emotional regulation scores among normal-weight teens (β = −0.46, p < 0.001) but not among overweight/obese teens (β = 0.32, p > 0.10). Higher scores on emotion regulation were significantly associated with lower emotional eating at high (β = −1.59, p < 0.001) and low (β = −1.00, p < 0.01) levels of negative body image. Engagement in emotional eating was predicted by higher negative body image among overweight/obese teens only (β = 0.70, p < 0.001). Our findings show that while better childhood emotion regulation skills are associated with lower emotional eating, weight status and negative body image influence this link and should be considered as important foci in future interventions that aim to reduce emotional eating in adolescence.

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Differences in Salivary Proteins as a Function of PROP Taster Status and Gender in Normal Weight and Obese Subjects

Molecules ◽

10.3390/molecules26082244 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2244

Author(s):

Melania Melis ◽

Mariano Mastinu ◽

Stefano Pintus ◽

Tiziana Cabras ◽

Roberto Crnjar ◽

...

Keyword(s):

Food Preferences ◽

Specific Weight ◽

Normal Weight ◽

Nutrition Status ◽

Salivary Proteins ◽

Specific Proteins ◽

Obese Subjects ◽

And Gender ◽

Cystatin Sn

Taste plays an important role in processes such as food choices, nutrition status and health. Salivary proteins contribute to taste sensitivity. Taste reduction has been associated with obesity. Gender influences the obesity predisposition and the genetic ability to perceive the bitterness of 6-n-propylthiouracil (PROP), oral marker for food preferences and consumption. We investigated variations in the profile of salivary proteome, analyzed by HPLC-ESI-MS, between sixty-one normal weight subjects (NW) and fifty-seven subjects with obesity (OB), based on gender and PROP sensitivity. Results showed variations of taste-related salivary proteins between NW and OB, which were differently associated with gender and PROP sensitivity. High levels of Ps-1, II-2 and IB-1 proteins belonging to basic proline rich proteins (bPRPs) and PRP-1 protein belonging to acid proline rich proteins (aPRPs) were found in OB males, who showed a lower body mass index (BMI) than OB females. High levels of Ps-1 protein and Cystatin SN (Cyst SN) were found in OB non-tasters, who had lower BMI than OB super-tasters. These new insights on the role of salivary proteins as a factor driving the specific weight gain of OB females and super-tasters, suggest the use of specific proteins as a strategic tool modifying taste responses related to eating behavior.

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Investigation of gene–environment interactions in relation to tic severity

Journal of Neural Transmission ◽

10.1007/s00702-021-02396-y ◽

2021 ◽

Author(s):

Mohamed Abdulkadir ◽

Dongmei Yu ◽

Lisa Osiecki ◽

Robert A. King ◽

Thomas V. Fernandez ◽

...

Keyword(s):

Tourette Syndrome ◽

Association Studies ◽

Autism Spectrum ◽

Environment Interaction ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Linear Regression Models ◽

Compulsive Disorder ◽

Gene Environment ◽

Tic Severity

AbstractTourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies.

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Role of urinary NGAL and KIM-1 as biomarkers of early kidney injury in obese prepubertal children

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0138 ◽

2020 ◽

Vol 33 (9) ◽

pp. 1183-1189 ◽

Cited By ~ 1

Author(s):

Nella Polidori ◽

Cosimo Giannini ◽

Roberta Salvatore ◽

Piernicola Pelliccia ◽

Adriana Parisi ◽

...

Keyword(s):

Cystatin C ◽

Kidney Injury ◽

Normal Weight ◽

Model Assessment ◽

Urinary Ngal ◽

Obese Children ◽

Prepubertal Children ◽

Ultrasound Evaluation ◽

Kidney Length ◽

Obese Subjects

AbstractObjectivesChildhood obesity is an important cause of end-stage renal disease. To date, available markers do not characterize kidney changes, especially in the early stages. kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are already detected before the onset of proteinuria or alterations of glomerular filtration rate and thus might represent biomarkers that directly reflect kidney injury.MethodsWe characterize kidney injury in a group of 40 obese-prepubertal children compared to 29-healthy age- and gender matched-peers. Anthropometric measurements and body composition were determined. Fasting blood samples were collected for measurement of insulin, glucose, lipid profile, transaminases, cystatin C and creatinine. Urine samples were collected to assess urinary NGAL, KIM-1 and urinary isoprostanes. Kidney length was measured with ultrasound evaluation. Differences between the two groups were evaluated by Mann–Whitney U test, and Spearman correlation analysis was used to explore relationship between variables.ResultsTriglycerides, alanine transaminase (ALT), glucose, insulin, homeostasis model assessment insulin resistance, triglycerides/high-density lipoprotein (HDL)-cholesterol ratio and cystatin C values were significantly higher in obese children than normal weight peers. Creatinine values were normal and similar between the two groups, while isoprostanes were higher in obese. Obese children had larger kidney sizes, indicating organ hypertrophy. NGAL and KIM-1 were increased in obese children compared to controls. A significant association between NGAL and KIM-1 with adiposity indices, insulin status and markers of oxidative stress postulated a possible effect of obesity in inducing kidney abnormalities. KIM-1 and NGAL are directly related respectively to cystatin C and isoprostanes, supporting the ability of these biomarkers in reflecting early kidney damages in obese subjects.ConclusionsThese findings suggest that obese subjects exhibit a certain degree of renal damage before kidney function loss.

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Subcutaneous Injection Depth Does Not Affect the Pharmacokinetics or Glucodynamics of Insulin Lispro in Normal Weight or Healthy Obese Subjects

Journal of Diabetes Science and Technology ◽

10.1177/1932296815573865 ◽

2015 ◽

Vol 9 (4) ◽

pp. 824-830 ◽

Cited By ~ 8

Author(s):

Amparo de la Peña ◽

Kwee P. Yeo ◽

Helle Linnebjerg ◽

Edward Catton ◽

Shobha Reddy ◽

...

Keyword(s):

Insulin Lispro ◽

Subcutaneous Injection ◽

Normal Weight ◽

Obese Subjects ◽

Injection Depth ◽

Healthy Obese

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Alexithymia in a Clinical Sample of Obese Women

Psychological Reports ◽

10.2466/pr0.1997.80.2.387 ◽

1997 ◽

Vol 80 (2) ◽

pp. 387-394 ◽

Cited By ~ 20

Author(s):

A. Morosin ◽

G. Riva

Keyword(s):

Eating Disorder ◽

Minnesota Multiphasic Personality Inventory ◽

Clinical Sample ◽

Normal Weight ◽

Eating Attitude ◽

Obese Women ◽

Test Analysis ◽

Eating Attitude Test ◽

Attitude Test ◽

Obese Subjects

The purpose was to examine the rate of alexithymia as measured by the Toronto Alexithymia Scale in a clinical sample of obese women without Binge Eating Disorder. Subjects included 165 inpatients in an eating disorder unit and 135 normal-weight individuals (comparison group). The obese subjects also completed a series of tests including the Minnesota Multiphasic Personality Inventory, the Anxiety Scale Questionnaire, and the Eating Attitude Test. Analysis showed that the subgroups of obese persons differ in important ways and cannot necessarily be treated, studied, or understood through a single paradigm. Alexithymic behaviour, too, was not characteristic of obesity, but it was present only in the subgroup of subjects with psychopathological characteristics.

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Independent and combined associations between fast-food outlet exposure and genetic risk for obesity: a population-based, cross-sectional study in the UK

BMC Medicine ◽

10.1186/s12916-021-01902-z ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Thomas Burgoine ◽

Pablo Monsivais ◽

Stephen J. Sharp ◽

Nita G. Forouhi ◽

Nicholas J. Wareham

Keyword(s):

Genetic Risk ◽

Fast Food ◽

Genetic Risk Score ◽

Population Based ◽

Overweight And Obesity ◽

Nucleotide Polymorphisms ◽

Food Outlet ◽

Cross Sectional ◽

Fast Food Outlet ◽

Common Genetic Variants

Abstract Background Characteristics of the built environment, such as neighbourhood fast-food outlet exposure, are increasingly recognised as risk factors for unhealthy diet and obesity. Obesity also has a genetic component, with common genetic variants explaining a substantial proportion of population-level obesity susceptibility. However, it is not known whether and to what extent associations between fast-food outlet exposure and body weight are modified by genetic predisposition to obesity. Methods We used data from the Fenland Study, a population-based sample of 12,435 UK adults (mean age 48.6 years). We derived a genetic risk score associated with BMI (BMI-GRS) from 96 BMI-associated single nucleotide polymorphisms. Neighbourhood fast-food exposure was defined as quartiles of counts of outlets around the home address. We used multivariable regression models to estimate the associations of each exposure, independently and in combination, with measured BMI, overweight and obesity, and investigated interactions. Results We found independent associations between BMI-GRS and risk of overweight (RR = 1.34, 95% CI 1.23–1.47) and obesity (RR = 1.73, 95% CI 1.55–1.93), and between fast-food outlet exposure and risk of obesity (highest vs lowest quartile RR = 1.58, 95% CI 1.21–2.05). There was no evidence of an interaction of fast-food outlet exposure and genetic risk on BMI (P = 0.09), risk of overweight (P = 0.51), or risk of obesity (P = 0.27). The combination of higher BMI-GRS and highest fast-food outlet exposure was associated with 2.70 (95% CI 1.99–3.66) times greater risk of obesity. Conclusions Our study demonstrated independent associations of both genetic obesity risk and neighbourhood fast-food outlet exposure with adiposity. These important drivers of the obesity epidemic have to date been studied in isolation. Neighbourhood fast-food outlet exposure remains a potential target of policy intervention to prevent obesity and promote the public’s health.

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