A Nutrigenetic Strategy for Reducing Blood Lipids and Low-Grade Inflammation in Adults with Obesity and Overweight.

The pathogenesis of obesity and dyslipidemia involves genetic factors, such as polymorphisms related to lipid metabolism alterations predisposing their development. This study aimed to evaluate the effect of a nutrigenetic intervention on the blood lipid levels, body composition, and inflammation markers of adults with obesity and overweight. Eleven genetic variants associated with dyslipidemias in Mexicans were selected, and specific nutrigenetic recommendations for these polymorphisms were found. One hundred and one adults were recruited and assigned to follow either a standard or nutrigenetic diet for eight weeks. Anthropometric, biochemical, body composition, and inflammation markers were evaluated through standardized methods. Weighted genetic risk scores (wGRSs) were computed using the study polymorphisms. After intervention, both diets significantly decreased the anthropometric parameters and body composition (p < 0.05). Only the nutrigenetic diet group showed significant reductions in VLDL-c (p = 0.001), triglycerides (p = 0.002), TG:HDL (p = 0.002), IL-6 (p = 0.002), and TNF-α (p = 0.04). wGRSs had a high impact on the ΔTGs and ΔVLDL-c of both groups (standard diet: ΔTGs: Adj R2 = 0.69, p = 0.03; ΔVLDL-c: Adj R2 = 0.71, p = 0.02; nutrigenetic diet: ΔTGs: Adj R2 = 0.49, p = 0.03 and ΔVLDL-c: R2 = 0.29, p = 0.04). This nutrigenetic intervention improved lipid abnormalities in patients with excessive body weight. Hence, nutrigenetic strategies could be coadjuvant tools and enhance the standard dietary treatment for cardiometabolic diseases.

Lipid-Related Genetic Variants for Personalized Dietary Interventions: A Systematic Review.

Dyslipidemias are known risk factors for chronic diseases. Precision nutrition interventions are designed according to characteristics, such as diet, phenotype, and genotype. This systematic review aims to define a panel of genetic variants associated with lipid abnormalities that could be later used in nutrigenetic intervention studies. A systematic review is conducted following the PRISMA-P. Studies published from January 2010 to December 2020 in English language and humans are included from PubMed and ScienceDirect databases. Articles that demonstrate a strong association between polymorphisms (single nucleotide variation) of genes involved in lipid metabolism and increased risk for dyslipidemia are included. A total of 3031 articles are screened, but only 51 articles fulfill the inclusion criteria. The genes included are FABP2, MTTP related to CM synthesis and secretion; LPL, LIPC involved in triglyceride hydrolysis; CETP, APOA1, LCAT, ABCA1, and APOA5 related to lipoprotein metabolism, and APOE, LDLR, SCARB1, APOC3 involved in lipid clearance. In this systematic review, genetic variants related to chylomicron synthesis, triglyceride hydrolysis, lipoprotein metabolism, and lipid clearance demonstrate a strong association with lipid abnormalities, which can be used to design precision nutrition interventions that may help to prevent and treat dyslipidemia effectively.

What do we know about nutrient-based strategies targeting molecular mechanisms associated with obesity-related fatty liver disease?

Obesity is a risk factor for developing nonalcoholic fatty liver disease (NAFLD), and the associated molecular mechanisms could be targeted with nutrient-based strategies. Therefore, it is necessary to review the current mechanisms to propose further treatments. Obesity facilitates the onset of insulin resistance, lipidic abnormalities, hepatic fat accumulation, lipid peroxidation, mitochondrial dysfunction, excessive reactive oxygen species (ROS) production, and inflammation, all related to further steatosis progression and fibrosis. Microbiota alterations can also influence liver disease by the translocation of pathogenic bacteria, energy extraction from short chain fatty acids (SCFAs), intestinal suppression of the expression of fasting-induced adipose factor (FIAF), reduction of bile acids, and altered choline metabolism. There are also genetic polymorphisms in metabolic proteins that predispose to a higher risk of liver diseases, such as those found in the patatin-like phospholipase domain-containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) or also known as lysophosphatidylinositol acyltransferase 1 (LPIAT1), transmembrane channel-like 4 genes (TMC4), fat mass and obesity-associated protein (FTO), the b Klotho (KLB) and carboxylesterase (CES1). No clear dietary guidelines target all mechanisms related to NAFLD development and progression. However, energy and carbohydrate intake restriction, regular physical exercise, supplementation of antioxidants, and restoration of gut microbiota seem to have beneficial effects on the new proposed features of NAFLD.

Anti-hepatitis B virus activity of food nutrients and potential mechanisms of action.

Hepatitis B virus (HBV) is endemic in many parts of the world and is a significant cause of chronic liver damage and hepatocellular carcinoma. HBV therapeutics vary according to the disease stage. The best therapeutic option for patients with end-stage liver disease is liver transplantation, while for chronic patients, HBV infection is commonly managed using antivirals (nucleos(t)ides analogs or interferons). However, due to the accessibility issues and the high cost of antivirals, most HBV patients do not have access to treatment. These complications have led researchers to reconsider treatment approaches, such as nutritional therapy. This review summarizes the nutrients reported to have antiviral activity against HBV and their possible mechanism of action. Recent studies suggest resveratrol, vitamin E, lactoferrin, selenium, curcumin, luteolin-7-O-glucoside, moringa extracts, chlorogenic acid, and epigallocatechin-3-gallate may be beneficial for patients with hepatitis B. The anti-HBV effect of most of these nutrients has been analyzed in vitro and in animal models. Different antiviral and hepatoprotective mechanisms have been proposed for these nutrients, such as the activation of antioxidant and anti-inflammatory pathways, regulation of metabolic homeostasis, epigenetic control, activation of the p53 gene, inhibition of oncogenes, inhibition of virus entry, and induction of autophagosomes. In conclusion, scientific evidence indicates that HBV replication, transcription, and expression of viral antigens can be affected directly by nutrients. In the future, these nutrients may be considered to develop appropriate nutritional management for patients with hepatitis B.

Personalized Dietary Recommendations Based on Lipid-Related Genetic Variants: A Systematic Review.

Background: Obesity and dyslipidemias are risk factors for developing cardiovascular diseases, the leading causes of morbidity and mortality worldwide. The pathogenesis of these diseases involves environmental factors, such as nutrition, but other aspects like genetic polymorphisms confer susceptibility to developing obesity and dyslipidemias. In this sense, nutrigenetics is being used to study the influence of genetic variations on the circulating lipid responses promoted by certain nutrients or foods to provide specific dietary strategies considering the genetic factors in personalized nutrition interventions. Objective: To identify throughout a systematic review the potential nutrigenetic recommendations that demonstrate a strong interaction between gene-diet and circulating lipid variations. Methods: This systematic review used the PRISMA-Protocol for manuscript research and preparation using PubMed and ScienceDirect databases. Human studies published in English from January 2010 to December 2020 were included. The main results were outcomes related to gene-diet interactions and plasmatic lipids variation. Results: About 1,110 articles were identified, but only 38 were considered to fulfill the inclusion criteria established based on the reported data. The acquired information was organized based on gene-diet interaction with nutrients and components of the diet and dietary recommendation generated by each interaction: gene-diet interaction with dietary fats, carbohydrates or dietary fiber, gene-diet interaction with nutraceutical or dietary supplementation, and gene-diet interaction with proteins. Conclusion: Findings included in this systematic review indicated that a certain percentage of dietary macronutrients, the consumption of specific amounts of polyunsaturated or monounsaturated fatty acids, as well as the ingestion of nutraceuticals or dietary supplements could be considered as potential strategies for the development of a wide range of nutrigenetic interventions since they have a direct impact on the blood levels of lipids. In this way, specific recommendations were identified as potential tools in developing precision diets and highlighted the importance of personalized nutrition. These recommendations may serve as a possible strategy to implement as dietary tools for the preventive treatment and control alterations in lipid metabolism. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021248816, identifier [CRD42021248816].

Influence of a Nutrigenetic Intervention on Self-Efficacy, Emotions, and Rewarding Behaviors in Unhealthy Eating among Mexicans: An Exploratory Pilot Study.

The Genome-based Mexican (GENOMEX) diet is a strategy for preventing and managing obesity. Emotion and eating behavior in the context of a nutrigenetic intervention have not been thoroughly studied. We aimed to explore the influence of the GENOMEX diet on emotions, self-efficacy, and rewarding behaviors in unhealthy eating among subjects with risk factors for obesity-related chronic diseases. Twenty-eight subjects included in the six-month GENOMEX intervention answered questions regarding emotions that influence food consumption. Additionally, the Patient Health Questionnaire (PHQ-9) and the Reward-based eating drive scale (RED) were applied. In the study, minimal, mild, moderate, and severe depression were present in 46.4%, 39.3%, 10.7%, and 3.6%, respectively. RED did not change, but it correlated with a higher intake of fats (r2 = 0.684, ß = 2.066, p = 0.003). Mood influenced unhealthy eating in 71.7% of subjects, and 76.9% experienced binge episodes triggered by anxiety. Sugars were the most consumed foods during binge episodes (42.2%). Both low self-efficacy levels and binge episodes were associated with high consumption of unhealthy foods. After the intervention, 10.7% of subjects reported a high level of self-efficacy. In conclusion, a culturally acceptable and genetically compatible regional Mexican food diet reduced negative emotions and unhealthy eating while increasing self-efficacy.

Adherence to a Fish-Rich Dietary Pattern Is Associated with Chronic Hepatitis C Patients Showing Low Viral Load: Implications for Nutritional Management.

Hepatitis C virus (HCV) infection is influenced by genetic (e.g., APOE polymorphisms) and environmental factors between the virus and the host. HCV modulates the host's lipid metabolism but dietary components influence lipids and in vitro HCV RNA replication. Few data exist on the role of dietary features or patterns (DPs) in HCV infection. Herein, we aimed to evaluate the nutritional profiles of chronic HCV (CHC) and spontaneous clearance (SC) Mexican patients in the context of APOE alleles and their correlation with HCV-related variables. The fibrosis-related APOEε3 allele prevailed in CHC and SC patients, who had four DPs ("meat and soft drinks", DP1; "processed animal and fried foods", DP2; "Mexican-healthy", DP3; and "fish-rich", DP4). In CHC subjects, polyunsaturated fatty acid intake (PUFA ≥ 4.9%) was negatively associated, and fiber intake (≥21.5 g/day) was positively associated with a high viral load (p < 0.036). High adherence to fish-rich DP4 was associated with a higher frequency of CHC individuals consuming PUFA ≥ 4.9% (p = 0.004) and low viral load (p = 0.036), but a lower frequency of CHC individuals consuming fiber ≥21.5 g/day (p = 0.038). In SC and CHC individuals, modifying unhealthy DPs and targeting HCV-interacting nutrients, respectively, could be part of a nutritional management strategy to prevent further liver damage.

A Regionalized Genome-Based Mexican Diet Improves Anthropometric and Metabolic Parameters in Subjects at Risk for Obesity-Related Chronic Diseases.

Obesity-related chronic diseases (CD) are highly prevalent in Mexicans who show moderate to high frequencies of diet-related adaptive gene (DRAG) polymorphisms and recent shifts in traditional dietary habits and lifestyles. This study first evaluated the effects of a regionalized genome-based Mexican (GENOMEX) diet on anthropometric and biochemical parameters and, subsequently their relationship with the genetic profile of DRAG polymorphisms in subjects with metabolic risk factors for obesity-related CD. Thirty-seven eligible subjects underwent a 24-week dietary intervention with a GENOMEX diet. The DRAG polymorphisms were determined by an allelic discrimination real-time assay to evaluate their association with the clinical response to diet. The GENOMEX diet significantly improved anthropometric parameters such as total weight, body mass index, waist circumference, and body fat percentage, with an average weight loss of 6.6% (5.3 ± 5.3 kg). The frequency of subjects with insulin resistance, hypertriglyceridemia and elevated VLDL-c (48.5% vs. 24.2%, p = 0.041; 45.5% vs. 12.1%, p = 0.003; and 39.4% vs. 15.2%, p = 0.027, baseline vs. 24-weeks, respectively) was reduced. A more significant favorable effect in HOMA-IR and insulin was observed in MTHFR 677T adaptive allele carriers, but no other DRAG polymorphism was associated with clinical changes. The GENOMEX diet improved the metabolic risk factors for obesity-related CD. The recommendation and habitual consumption of a traditional Mexican diet based on knowledge of the population´s genetic and cultural history may be effective in preventing current obesity-related CD.

High prevalence of nonalcoholic steatohepatitis and abnormal liver stiffness in a young and obese Mexican population.

OBJECTIVE: To identify nonalcoholic steatohepatitis (NASH) and liver stiffness in Mexican subjects with different body mass index (BMI). METHODS: A cross-sectional study was conducted in 505 adults. Risk for NASH was defined as the presence of one or more of the following biochemical and metabolic parameters (BMPs): fasting glucose ≥100 mg/dl, triglycerides (TG) ≥150 mg/dl, homeostatic model assessment of insulin resistance (HOMA-IR) ≥2.5, aspartate aminotransferase (AST) >54 IU/L and alanine aminotransferase (ALT) >42 IU/L. Body mass index measurement and nutritional assessment were performed by standard procedures. Liver fibrosis stage was determined by liver stiffness measurement using transitional elastography (TE) or by liver biopsy (LB). RESULTS: Risk for NASH was 57% (290/505). Most BMPs values incremented by BMI category. Among 171 at-risk patients, 106 subjects were evaluated by TE and 65 subjects by LB. Abnormal liver stiffness (≥6.0 kPa) was prevalent in 54% (57/106) of the cases, whereas by LB, 91% (59/65) of patients with obesity had NASH and liver fibrosis. Furthermore, liver fibrosis was prevalent in 46% (6/13) in normal weight individuals, whereas 4.6% (3/65) of patients with a BMI ≥ 35 kg/m2 showed no histopathological abnormalities. Overall, 67.8% (116/171) of the patients had abnormal liver stiffness or NASH. The normal weight patients with liver damage consumed relatively a higher fat-rich diet compared to the other groups whereas the remaining subgroups shared a similar dietary pattern. CONCLUSION: Young patients with overweight and obesity showed a high prevalence of altered BMPs related to abnormal liver stiffness assessed by TE and NASH by LB. Early diagnostic strategies are required to detect the risk for NASH and avoid further liver damage in populations with a rising prevalence of obesity by defining the risk factors involved in the onset and progression of NASH.

DRD2/ANKK1 TaqI A1 polymorphism associates with overconsumption of unhealthy foods and biochemical abnormalities in a Mexican population.

PURPOSE: The dopamine receptor 2/ankyrin repeat domain and content kinase 1 (DRD2/ANKK1) TaqIA polymorphism (rs1800497) has been associated with rewarding behaviors. This study aimed to investigate the association of DRD2/ANKK1 TaqIA polymorphism with the dietary intake, the intake frequency of food groups and biochemical profile in Mexican mestizo subjects. METHODS: A cross-sectional/analytical study with 276 Mexican subjects was performed. Dietary intake was assessed with a 24-h recall and a food frequency questionnaire (FFQ). An allelic discrimination assay evaluated DRD2/ANKK1 TaqIA genotypes. Anthropometric and biochemical data were evaluated. RESULTS: Genotype frequencies were A1A1 (18.48%), A1A2 (45.29%) and A2A2 (36.23%). TaqI A1 allele carriers had a higher intake of carbohydrates (p = 0.038), meats (p = 0.005), fried dishes (p = 0.039), and sugars (p = 0.009). Male TaqI A1 carriers consumed more carbohydrates (p = 0.009) and meats (p = 0.018) while females consumed fewer legumes (p = 0.005). TaqI A1 carriers had glucose (p = 0.037) and triglycerides (p = 0.011) abnormalities. TaqI A1 was associated with higher risk of consumption of unhealthy foods such as fried dishes (OR 3.79, 95% CI 1.53-9.35, p = 0.002) and meats (OR 2.31, 95% CI 1.32-4.05, p = 0.003), and lower healthy foods (OR 1.89, 95% CI 1.04-3.29, p = 0.038). TaqI A1 allele was associated with risk of abnormal glucose, triglycerides, and VLDL levels (OR 2.148, 95% CI 1.068-4.322, p = 0.036; OR 1.999, 95% CI 1.194-3.348, p = 0.011; OR 2.021, 95% CI 1.203-3.392, p = 0.007), respectively. CONCLUSIONS: The presence of the TaqI A1 allele in Mexicans is a genetic risk factor for detrimental dietary quality that may predispose to metabolic disturbances. LEVEL OF EVIDENCE: Level III, case-control analytic study.

Dopamine D2 receptor polymorphism (C957T) is associated with sugar consumption and triglyceride levels in West Mexicans.

Genetic variations in the dopamine receptor D2 (DRD2) may alter dopamine signaling and modify the rewarding effects of food. This study aimed to analyze the association of the C957T DRD2 polymorphism with sugar consumption in West Mexican subjects. In a cross-sectional and analytical study, a total of 215 Mexican subjects were enrolled. DRD2 genotyping was performed by an allelic discrimination assay. Habitual dietary intake and the biochemical profile were evaluated. Genotype frequencies of the C957T DRD2 polymorphism were CC (12.1%), CT (40.9%) and TT (47.0%). Carriers of the CC genotype had a higher intake of sugar (g/day) than heterozygotes (67.4 g vs. 41.3 g, p = 0.001) and TT homozygotes (67.4 g vs. 45.2 g, p = 0.004). Also, the habitual consumption of soda (daily or at least 3 times per week) was more frequent among CC genotype carriers compared with heterozygotes (81% vs. 51%, p = 7.5 × 10-6) and TT homozygotes (81% vs. 57%, p = 2.4 × 10-4). Furthermore, the CC genotype was associated with elevated serum triglyceride levels (>150 mg/dL) than the CT genotype (OR = 2.80, 95% CI 1.08-7.24, p = 0.034). In conclusion, our results suggest a genetic background associated with sugar consumption among West Mexicans, which may contribute to increases in serum triglyceride levels.

Tailoring Nutritional Advice for Mexicans Based on Prevalence Profiles of Diet-Related Adaptive Gene Polymorphisms.

Diet-related adaptive gene (DRAG) polymorphisms identified in specific populations are associated with chronic disorders in carriers of the adaptive alleles due to changes in dietary and lifestyle patterns in recent times. Mexico's population is comprised of Amerindians (AM) and Mestizos who have variable AM, European (EUR) and African genetic ancestry and an increased risk of nutrition-related chronic diseases. Nutritional advice based on the Mexican genome and the traditional food culture is needed to develop preventive and therapeutic strategies. Therefore, we aimed to provide a prevalence profile of several DRAG polymorphisms in the Mexican population, including Central West (CW) Mexico subpopulations. Geographic heat maps were built using ArcGIS10 (Esri, Redlands, CA, USA) software, based on the published data of the MTHFR C677T (rs1801133), ABCA1 Arg230Cys (rs9282541), APOE T388C (rs429358)/C526T (rs7412), LCT C-13910T (rs4988235) polymorphisms and AMY1 copy number variation (CNV). Also, new data obtained by allelic discrimination-real-time polymerase chain reaction (RT-PCR) assays for the MTHFR, ABCA1, and APOE polymorphisms as well as the AMY1 CNV in the CW Mexico subpopulations with different proportions of AM and EUR ancestry were included. In the CW region, the highest frequency of the MTHFR 677T, ABCA1 230C and APOE ε4 adaptive alleles was observed in the AM groups, followed by Mestizos with intermediate AM ancestry. The LCT-13910T allele frequency was highest in Mestizos-EUR but extremely low in AM, while the AMY1 diploid copy number was 6.82 ± 3.3 copies. Overall, the heat maps showed a heterogeneous distribution of the DRAG polymorphisms, in which the AM groups revealed the highest frequencies of the adaptive alleles followed by Mestizos. Given these genetic differences, genome-based nutritional advice should be tailored in a regionalized and individualized manner according to the available foods and Mexican traditional food culture that may lead to a healthier dietary pattern.

Early Detection of Liver Damage in Mexican Patients with Chronic Liver Disease.

BACKGROUND AND OBJECTIVE: Liver cirrhosis is usually detected at the later stages of disease. This study is aimed to detect liver damage in patients with chronic liver disease using transitional elastography (TE) and to assess the biochemical parameters associated with liver damage. METHODS: In 578 patients, chronic liver disease based on etiology was diagnosed by clinical and laboratory tests. Liver damage was evaluated with TE (FibroScan®), while its association with biochemical parameters was performed using the logistic regression tests. RESULTS: Overall, the main etiologies of liver damage were hepatitis C virus (HCV) (37%), alcoholic liver disease (ALD) (33%) and non-alcoholic steatohepatitis (NASH) (26%). Patients were 40 to 50 years of age. ALD and hepatitis B prevailed in men, whereas HCV and NASH in women. The stages of fibrosis were F0 (n = 121, 21%), F1 (n = 122, 21%), F2 (n = 58, 10%), F3 (n = 46, 8%) and F4 (n = 87, 15%). In patients with liver cirrhosis, ALD (n = 96/217, 45%), HCV (n = 94/217, 43%) and NASH (n = 21/217, 10%) were the leading etiologies. Platelets count (OR=3.31, 95%CI 1.61-6.78), glucose (OR=3.07, 95%CI 1.50-6.26), gamma-glutamyl-transferase (OR=3.60, 95%CI 1.79-7.25), albumin (OR=3.89, 95%CI 1.61-9.36), and total bilirubin (OR=3.93, 95%CI 1.41-10.91) were associated to advanced stages of fibrosis (F3-F4) regardless of etiology. The concordance and positive predictive values of these parameters were higher as compared to other scores. CONCLUSION: Asymptomatic liver disease due to HCV, ALD and NASH prevailed in young adults. Advanced liver damage assessed by TE was associated with five biochemical parameters. In conjunction, both methodologies may be useful for the early detection of fibrosis and cirrhosis in Latin America.

Genes, emotions and gut microbiota: The next frontier for the gastroenterologist.

Most medical specialties including the field of gastroenterology are mainly aimed at treating diseases rather than preventing them. Genomic medicine studies the health/disease process based on the interaction of the human genes with the environment. The gastrointestinal (GI) system is an ideal model to analyze the interaction between our genes, emotions and the gut microbiota. Based on the current knowledge, this mini-review aims to provide an integrated synopsis of this interaction to achieve a better understanding of the GI disorders related to bad eating habits and stress-related disease. Since human beings are the result of an evolutionary process, many biological processes such as instincts, emotions and behavior are interconnected to guarantee survival. Nourishment is a physiological need triggered by the instinct of survival to satisfy the body's energy demands. The brain-gut axis comprises a tightly connected neural-neuroendocrine circuitry between the hunger-satiety center, the dopaminergic reward system involved in the pleasure of eating and the gut microbiota that regulates which food we eat and emotions. However, genetic variations and the consumption of high-sugar and high-fat diets have overridden this energy/pleasure neurocircuitry to the point of addiction of several foodstuffs. Consequently, a gut dysbiosis generates inflammation and a negative emotional state may lead to chronic diseases. Balancing this altered processes to regain health may involve personalized-medicine and genome-based strategies. Thus, an integrated approach based on the understanding of the gene-emotions-gut microbiota interaction is the next frontier that awaits the gastroenterologist to prevent and treat GI disorders associated with obesity and negative emotions.