FTO rs9939609: T>A Variant and Physical Inactivity as Important Risk Factors for Class III Obesity: A Cross-Sectional Study.

BACKGROUND: The prevalence of obesity has been increasing worldwide. It has been reported that physiological and environmental factors such as diet, culture, physical activity, and genetics are the principal factors related to obesity. The fat mass and obesity-associated (FTO) gen variant (rs9939609: T>A) has been associated with class III obesity. The A variant has been correlated with anthropometric and metabolic alterations. Therefore, the purpose of this study was to analyze the association of the FTO rs9939609: T>A variant and environmental factors with clinical, anthropometric, and biochemical variables in subjects with class III obesity. RESULTS: The A variant frequency was higher in the class III obesity group compared with the normal weight group (44% vs. 25%, p < 0.001). Subjects with the AA genotype had a higher body mass index (BMI) than those with the AT genotype (35.46 kg/m2 (31-39.8) vs. 26.91 kg/m2 (23.7-30), p = 0.005). Women with the AA genotype showed higher waist circumferences than the AT group (101.07 cm (90.9-111.1) vs. 85.45 cm (77-93.8) p = 0.047). The FTO A variant increases the risk by 3.54 times and physical inactivity increases the risk by 6.37 times for class III obesity. CONCLUSIONS: Our results suggest that among the studied variables, those most related to class III obesity were the FTO risk genotype (A allele) and physical inactivity.

Association between the FAAH C385A variant (rs324420) and obesity-related traits: a systematic review.

BACKGROUND: Overweight and obesity are the consequence of a sustained positive energy balance. Twin studies show high heritability rates pointing to genetics as one of the principal risk factors. By 2022, genomic studies led to the identification of almost 300 obesity-associated variants that could help to fill the gap of the high heritability rates. The endocannabinoid system is a critical regulator of metabolism for its effects on the central nervous system and peripheral tissues. Fatty acid amide hydrolase (FAAH) is a key enzyme in the inactivation of one of the two endocannabinoids, anandamide, and of its congeners. The rs324420 variant within the FAAH gene is a nucleotide missense change at position 385 from cytosine to adenine, resulting in a non-synonymous amino acid substitution from proline to threonine in the FAAH enzyme. This change increases sensitivity to proteolytic degradation, leading to reduced FAAH levels and increased levels of anandamide, associated with obesity-related traits. However, association studies of this variant with metabolic parameters have found conflicting results. This work aims to perform a systematic review of the existing literature on the association of the rs324420 variant in the FAAH gene with obesity and its related traits. METHODS: A literature search was conducted in PubMed, Web of Science, and Scopus. A total of 645 eligible studies were identified for the review. RESULTS/CONCLUSIONS: After the identification, duplicate elimination, title and abstract screening, and full-text evaluation, 28 studies were included, involving 28 183 individuals. We show some evidence of associations between the presence of the variant allele and higher body mass index, waist circumference, fat mass, and waist-to-hip ratio levels and alterations in glucose and lipid homeostasis. However, this evidence should be taken with caution, as many included studies did not report a significant difference between genotypes. These discordant results could be explained mainly by the pleiotropy of the endocannabinoid system, the increase of other anandamide-like mediators metabolized by FAAH, and the influence of gene-environment interactions. More research is necessary to study the endocannabinoidomic profiles and their association with metabolic diseases.

Pharmacomicrobiomics and Drug-Infection Interactions: The Impact of Commensal, Symbiotic and Pathogenic Microorganisms on a Host Response to Drug Therapy.

Microorganisms have a close relationship with humans, whether it is commensal, symbiotic, or pathogenic. Recently, it has been documented that microorganisms may influence the response to drug therapy. Pharmacomicrobiomics is an emerging field that focuses on the study of how variations in the microbiome affect the disposition, action, and toxicity of drugs. Two additional sciences have been added to complement pharmacomicrobiomics, namely toxicomicrobiomics, which explores how the microbiome influences drug metabolism and toxicity, and pharmacoecology, which refers to modifications in the microbiome as a result of drug administration. In this context, we introduce the concept of "drug-infection interaction" to describe the influence of pathogenic microorganisms on drug response. This review analyzes the current state of knowledge regarding the relevance of microorganisms in the host's response to drugs. It also highlights promising areas for future research and proposes the term "drug-infection interaction" as an extension of pharmacomicrobiomics.

The Inflammatory and Oxidative Status of Newly Diagnosed Class III and Class IV Lupus Nephritis, with Six-Month Follow-Up.

Lupus nephritis (LN) is the most frequent and severe complication of systemic lupus erythematosus (SLE). A prospective cohort with a six-month follow-up was performed. Twelve SLE patients diagnosed with LN Class III, twelve NL Class IV patients, and twelve healthy control subjects (HC) were included. SLE data, renal function, oxidants, antioxidants, and inflammation were determined at baseline and six-month follow-up. During the six-month follow-up, the SLE Disease Activity Index (SLEDAI-2K) decreased in both LN Class III (20.08 ± 6.92 vs. 11.92 ± 5.87, p < 0.001) and LN Class IV (25.33 ± 6.01 vs. 13.83 ± 5.52, p < 0.001) patients. Furthermore, the values of the C4 component also increased during follow-up for LN Class III (25.36 ± 6.34 vs. 30.91 ± 9.22, p = 0.027) and LN Class IV (12.18 ± 3.90 vs. 20.33 ± 8.95, p = 0.008) groups. Regarding inflammation markers, both groups presented decreased C-reactive protein (CRP), but this was only significant for patients with LN class III (7.93 ± 1.77 vs. 4.72 ± 3.23, p = 0.006). Renal function remained stable in both groups, with no changes in eGFR. Patients with LN Class III and Class IV showed higher baseline levels for lipoperoxides (Class III p < 0.01, Class IV p < 0.1) and carbonyl groups in proteins (Class III p < 0.01, Class IV p < 0.1) compared to HC. Moreover, both groups presented lower baseline values of total antioxidant capacity (Class III p < 0.01, Class IV p < 0.1) and catalase (Class III p < 0.01, Class IV p < 0.1) compared to HCs. However, antioxidant and oxidant markers did not show significant differences between baseline values and at six months for either of the two study groups. In conclusion, patients show an imbalance in the oxidative state characterized by the increase in the oxidants LPO and protein carbonyl groups and the decrease in the activity of the antioxidant enzymes TAC and CAT compared to HC. However, the patients did not present an increase in disease activity and renal function improvement. The glomerular filtration rate did not change during the length of the study, and SLEDAI -2K, C3, and C4 improved. The early co-management between Rheumatologists and Nephrologists is essential to prevent the rapid progression of LN. It would be interesting to administer antioxidant supplements to patients with a recent diagnosis of LN and evaluate its effect in a follow-up study.

10­Gingerol, a novel ginger compound, exhibits antiadipogenic effects without compromising cell viability in 3T3­L1 cells.

Obesity is defined as excessive fat accumulation that can be detrimental to health and currently affects a large part of the global population. Obesity arises from excessive energy intake along with a sedentary lifestyle and leads to adipocytes with aggravated hypertrophy. Strategies have been designed to prevent and treat obesity. Nutrigenomics may serve a role in prevention of obesity using bioactive compounds present in certain foods with anti-obesogenic effects. Ginger (Zingiber officinale Roscoe) contains gingerols, key bioactive compounds that inhibit hypertrophy and hyperplasia of adipocytes. The present study aimed to evaluate the antiadipogenic activity of 10-gingerol (10-G) in the 3T3-L1 cell line. Three study groups were formed: Negative (3T3-L1 preadipocytes) and positive control (mature 3T3-L1 adipocytes) and 10-G (3T3-L1 preadipocytes stimulated with 10-G during adipogenic differentiation). Cell viability and lipid content were evaluated by MTT assay and Oil Red O staining, respectively. mRNA expression of CCAAT enhancer-binding protein α (C/ebpα), peroxisome proliferator-activated receptor γ (Pparγ), mechanistic target of rapamycin complex (Mtor), sterol regulatory element binding transcription factor 1 (Srebf1), acetyl-coenzyme A carboxylase (Acaca), fatty acid binding protein 4 (Fabp4), and 18S rRNA (Rn18s), was quantified by quantitative PCR. The protein expression of C/EPBα was analyzed by western blot. In the 10-G group, lipid content was decreased by 28.83% (P<0.0001) compared with the positive control; notably, cell viability was not affected (P=0.336). The mRNA expression in the 10-G group was higher for C/ebpα (P<0.001) and lower for Acaca (P<0.001), Fabp4 (P<0.001), Mtor (P<0.0001) and Srebf1 (P<0.0001) compared with the positive control group, while gene expression of Pparγ did not present significant changes. The presence of 10-G notably decreased C/EBPα protein levels in 3T3-L1 adipocytes. In summary, the antiadipogenic effect of 10-G during the differentiation of 3T3-L1 cells into adipocytes may be explained by mRNA downregulation of adipogenic transcriptional factors and lipid metabolism-associated genes.

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.

FTO genotypes (rs9939609 T>A) are Associated with Increased Added Sugar Intake in Healthy Young Adults.

INTRODUCTION: Single-nucleotide polymorphism (SNP) rs9939609 in the FTO gene has been associated with dietary intake and appetite traits, mainly in participants with obesity; however, it remains widely unexplored in normal weight participants. Thus, the aims of this study were (1) to compare the changes in subjective appetite sensations, ghrelin, and insulin concentrations according to the SNP rs9939609 T>A in FTO and (2) to compare dietary intake between rs9939609 genotype groups in normal weight young participants. METHODS: We conducted a quasi-experimental study involving 88 normal weight participants to analyze subjective perception of appetite, hormonal response for hunger and satiety, and dietary intake according to the rs9939609 SNP. Participants received a standardized single breakfast. Visual analogue scales (VAS) were utilized for assessing the subjective perception of appetite at fasting and immediately after breakfast and at 30, 60, 90, and 120 min postprandially. Glucose, lipid profile, ghrelin, and insulin were measured at fasting and at 120 min after breakfast. Dietary intake was assessed with a 3-day food record. The SNP was determined by allelic discrimination with TaqMan probes. To compare dietetic, biochemical, and the subjective appetite sensations, Student t test, ANCOVA test, and the repeated measures ANOVA were used. The linear regression model and the linear mixed model were used for the association analysis. Pearson correlation was used to test the correlation between two quantitative variables. RESULTS: A total of 88 people participated, 81.8% were female, with a mean body mass index of 21.8 ± 2.0 kg/m2 and a mean age of 20.6 ± 2.0. Genotype frequencies of the rs9939609 SNP were 52% for the TT allele and 48% for the TA/AA. The subjective perception of appetite named hunger, fullness, satiety, desire to eat, and prospective food consumption were similar between genotypes of the rs9939609. Participants with the TA/AA genotype showed a higher intake of added sugar (p = 0.039) than TT participants. No differences were found in ghrelin, insulin, glucose, or lipid parameters between genotypes. CONCLUSION: Carriers of the A allele from FTO gene SNP rs9939609 may have an increased preference for foods, specifically for added sugars.

A Balanced Dietary Ratio of n-6:n-3 Polyunsaturated Fatty Acids Exerts an Effect on Total Fatty Acid Profile in RBCs and Inflammatory Markers in Subjects with Obesity.

The n-3 polyunsaturated fatty acids (PUFAs) can reduce inflammatory markers and may therefore be useful in obesity management. The aim of this study was to analyze the effect of supplementation with n-3 PUFAs on total fatty acid profile in red blood cells (RBCs), as well as biochemical and inflammatory markers, in subjects with obesity. The study consisted in a randomized placebo-controlled, double-blind clinical trial involving 41 subjects with obesity during a 4-month follow-up. Individuals were randomly assigned to two groups: n-3 PUFA supplementation (1.5 g fish oil) and placebo (1.5 g sunflower oil). Anthropometric, biochemical, dietetic, cytokine and total fatty acid profiles in RBCs were measured. Both groups increased their PUFA intake and DHA incorporation in RBCs. However, the placebo group showed a reduction in serum IL-8 and MCP-1 at the end of the study. A multiple linear regression model adjusted by body fat mass and sex showed that an increase in DHA in RBCs decreased the serum IL-8 levels in both study groups at the end of the study. Our results highlight the role of dietary DHA and n-3 supplementation usefulness in exerting beneficial anti-inflammatory effects.

FAAH Pro129Thr Variant Is Associated with Increased Cholesterol Levels in Normal-Weight Metabolically Unhealthy Subjects.

Introduction: The endocannabinoid system (ECS) plays an integral role in maintaining metabolic homeostasis, where an hyperactivation has been related with serum lipid alterations. The biological effects of ECS are limited by the activation of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) and by polyunsaturated fatty acid (PUFA) intake as precursors. The FAAH Pro129Thr variant has been associated with obesity in some populations. However, the association with metabolic phenotypes in the Mexican population has not been studied. This study aimed to analyze the association of the FAAH Pro129Thr variant with serum lipids and diet in Mexican adults with different metabolic phenotypes. Methods: This is a cross-sectional study with 306 subjects between 18 and 65 years of age. They were classified with normal weight (NW) or excess weight (EW) according to their body mass index (BMI). The EW group included individuals with overweight or obesity (BMI 25-39.9 kg/m2). The individuals were classified into two metabolic phenotypes, metabolically healthy and metabolically unhealthy (MUH), using the homeostatic model assessment of insulin resistance and the National Cholesterol Education Program-adenosine triphosphate III cutoff points for blood pressure, triglycerides, high-density lipoprotein cholesterol, and fasting glucose. Subjects with ≥2 of 5 altered parameters were classified as MUH. The FAAH Pro129Thr variant was determined by allelic discrimination with TaqMan® probes. Results: The total cholesterol and very low-density lipoprotein cholesterol levels were associated with the FAAH Pro129Thr variant in NW-MUH subjects. Moreover, a lower PUFA intake was found in EW-MUH subjects with the FAAH variant. Conclusions: FAAH Pro129Thr variant has an important role in lipid metabolism, especially in NW-MUH subjects. By contrast, a low dietary intake of endocannabinoid PUFA precursors may partly counteract the development of the altered lipid profile associated with overweight/obesity.

Physical Activity Protocols in Non-Alcoholic Fatty Liver Disease Management: A Systematic Review of Randomized Clinical Trials and Animal Models.

Non-alcoholic fatty liver disease (NAFLD) is closely associated with other metabolic disease and cardiovascular disease. Regular exercise reduces hepatic fat content and could be the first-line treatment in the management of NAFLD. This review aims to summarize the current evidence of the beneficial effects of exercise training and identify the molecular pathways involved in the response to exercise to define their role in the resolution of NAFLD both in animal and human studies. According to the inclusion criteria, 43 animal studies and 14 RCTs were included in this systematic review. Several exercise modalities were demonstrated to have a positive effect on liver function. Physical activity showed a strong association with improvement in inflammation, and reduction in steatohepatitis and fibrosis in experimental models. Furthermore, both aerobic and resistance exercise in human studies were demonstrated to reduce liver fat, and to improve insulin resistance and blood lipids, regardless of weight loss, although aerobic exercises may be more effective. Resistance exercise is more feasible for patients with NAFLD with poor cardiorespiratory fitness. More effort and awareness should be dedicated to encouraging NAFLD patients to adopt an active lifestyle and benefit from it its effects in order to reduce this growing public health problem.

Effect of Human Adenovirus 36 on Response to Metformin Monotherapy in Obese Mexican Patients with Type 2 Diabetes: A Prospective Cohort Study.

Human adenovirus 36 (HAdV-36) has been associated with obesity and changes in glucose and lipid metabolism. The virus has been reported to increase insulin sensitivity and paradoxically promote weight gain. Because of its effects on metabolism, infection with the virus could alter the response to several drugs used to treat type 2 diabetes (DM2), such as metformin. The aim of this study was to test whether HAdV-36 affects the response to metformin in a group of obese patients with DM2. METHODS: In a prospective cohort study, 103 obese patients with newly diagnosed DM2 were divided into two groups based on their HAdV-36 seropositivity (+HAdV-36 and -HAdV-36). Weight, glucose, cholesterol, triglycerides, body mass index, body fat percentage, and waist and hip circumference were measured and compared in both groups at baseline and after 45 days of metformin treatment. RESULTS: Only glucose was significantly lower in the +HAdV-36 group at baseline, while all other variables were similar between the two study groups. After 45 days of follow-up, it was observed that the effect of metformin did not differ between the groups, but the variables improved significantly after treatment. CONCLUSIONS: In this study, we did not find that HAdV-36 had an effect on the response to metformin in obese patients with DM2.

A mix of ginger phenols exhibits anti­adipogenic and lipolytic effects in mature adipocytes derived from 3T3­L1 cells.

The prevalence of obesity has increased rapidly worldwide. Obesity is characterized by excessive adipose tissue in the body, which is related to hyperplasia and hypertrophy in adipocytes. Ginger (Zingiber officinale Roscoe) is a medicinal plant that possesses an anti-obesogenic effect mostly attributed to gingerols, the most abundant bioactive compounds in ginger. The anti-adipogenic and lipolytic effects of these phenols have been shown when investigated individually. Therefore, the present study aimed to evaluate the lipolytic and anti-adipogenic activity of a mix of the main ginger phenols 6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 8-shogaol and 10-shogaol on the 3T3-L1 cell line. A total of four study groups were designed: Negative control (3T3-L1 preadipocytes); positive control (mature 3T3-L1 adipocytes); phenols-pre (3T3-L1 cells stimulated with the phenols mix during adipogenic differentiation); and phenols-post (mature 3T3-L1 adipocytes stimulated with the phenols mix). MTT viability cell assay and Oil Red O staining were performed. Glycerol concentration supernatants were determined using the VITROS 350 Chemistry System. Expression of mRNA was measured using qPCR. The treatment with a 2 µg/ml ginger phenol dose reduced the lipid content by 45.52±7.8 and 35.95±0.76% in the phenols-pre and -post group, respectively, compared with that in the positive control group. The phenols-post group presented a higher glycerol concentration in the supernatant compared with that in the positive control and the phenols-pre groups. The mRNA expression levels of CCAAT/enhancer-binding protein alpha, peroxisome proliferator activated receptor-γ, fatty acid-binding protein 4 and fatty acid synthase were higher in the phenols-pre and lower in the phenols-post groups, compared with those in the positive control group. To the best of our knowledge, the current study demonstrated for the first time the anti-adipogenic and lipolytic effects of a mix of the main bioactive compounds found in ginger, and it also established the basis to use this mix of phenols in in vivo studies and clinical trials.

Chronic Administration of Diethylnitrosamine and 2-Acetylaminofluorene Induces Hepatocellular Carcinoma in Wistar Rats.

This study aimed to analyze the biochemical, histological, and gene expression alterations produced in a hepatocarcinogenesis model induced by the chronic administration of diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) in Wistar rats. Thirteen rats weighing 180 to 200 g were divided into two groups: control and treated. Rats in the treated group were administered an intraperitoneal (i.p.) injection of DEN (50 mg/kg/week) and an intragastric (i.g.) dose of 2-AAF (25 mg/kg/week) for 18 weeks. The treated group had significant increases in their total cholesterol, HDL-C, AST, ALT, ALKP, and GGT levels. Furthermore, a histological analysis showed the loss of normal liver architecture with nuclear pleomorphism in the hepatocytes, atypical mitosis, and fibrous septa that were distributed between the portal triads and collagen fibers through the hepatic sinusoids. The gene expressions of 24 genes related to fibrosis, inflammation, apoptosis, cell growth, angiogenesis, lipid metabolism, and alpha-fetoprotein (AFP) were analyzed; only TGFß, COL1α1, CYP2E1, CAT, SOD, IL6, TNF-α, and ALB showed significant differences when both groups were compared. Additionally, lung histopathological alterations were found in the treated group, suggesting metastasis. In this model, the chronic administration of DEN+2-AAF induces characteristic alterations of hepatocellular carcinoma in Wistar rats without AFP gene expression changes, highlighting different signatures in hepatocellular carcinoma heterogeneity.

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.

Abdominal Obesity, Excessive Adiposity, and the Taq1B CETP Variant Are Positively Associated with Serum Lipid Levels in Mexican Women.

INTRODUCTION: Obesity is a prevalent multifactorial disease whose main complication is dyslipidemia. Serum lipid levels also depend on genetic factors including the Taq1B variant of the CETP gene, which is suggested to be influenced by environmental factors and adiposity. Therefore, this study aimed to determine the effect of the Taq1B CETP variant on serum lipid levels associated with anthropometrical variables. METHODS: 165 women from western Mexico were enrolled in this cross-sectional study. Weight and body fat were measured by bioimpedance and waist circumference with a measuring tape. Serum lipid levels were determined by dry chemistry. The Taq1B CETP variant was analyzed by allelic discrimination. RESULTS: Women with abdominal obesity and the B1B2/B2B2 genotype had significantly higher total cholesterol levels (195.17 [185.95-204.39] vs. 183 mg/dL [169.83-196.16], p = 0.007) and low density lipoprotein (118.84 [110.65-127.03] vs. 113.84 mg/dL [102.37-125.31], p = 0.037) than carriers of the B1B1 genotype. Likewise, subjects with excessive adiposity and the B1B2/B2B2 genotype showed significantly higher total cholesterol levels (195.05 [186.04-204.06] vs. 182.40 mg/dL [169.03-195.76], p = 0.003) than those with the B1B1 genotype. CONCLUSION: Women with abdominal obesity or excessive adiposity, who are also carriers of the B1B2/B2B2 genotype, have higher serum lipid levels than women with the B1B1 genotype.

Elevated Serum Low-Density Lipoproteins-Cholesterol Levels and B1B2/B2B2 CETP Genotype Are Positively Associated with Nonalcoholic Fatty Liver Disease in Women with Gallstone Disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is generated by the interaction between environmental and genetic factors, and the presence of metabolic alterations. Since Taq1B cholesteryl ester transfer protein (CETP) polymorphism is associated with abnormal serum lipid values, it could be related to NAFLD. The aim of this study was to determine the role of the Taq1B CETP polymorphism with serum lipids, anthropometric variables, and the extent of steatosis in Mexican-mestizo women with gallstone disease (GD). Methods: Sixty-two women were enrolled in this cross-sectional study. Serum lipids were determined by dry chemistry. The Taq1B CETP polymorphism was determined by allelic discrimination. CETP serum levels were measured by enzyme-linked immunosorbent assay, and the extent of steatosis with a biopsy staining with Oil-Red-O. Results: Subjects with the B1B2/B2B2 genotype had higher percentage of degree of steatosis than those with B1B1 (11.95% vs. 2.19%, P = 0.008). The B1B2/B2B2 genotype (odds ratio [OR] 3.90 [confidence interval {CI} 95% 1.891-8.536], P = 0.04) and an elevated low-density lipoproteins (LDL)-cholesterol (OR 3.54 [CI 95% 1.042-2.058, P = 0.039) significantly increase the risk for NAFLD. Conclusions: This study provides evidence that the B1B2/B2B2 genotype of CETP and the elevated LDL-cholesterol serum levels increase the risk of NAFLD in women with GD.

Association between the rs3812316 Single Nucleotide Variant of the MLXIPL Gene and Alpha-Linolenic Acid Intake with Triglycerides in Mexican Mestizo Women.

The carbohydrate response element binding protein (ChREBP) is a key transcription factor to understand the gene−diet−nutrient relationship that leads to metabolic diseases. We aimed to analyze the association between the rs17145750 and rs3812316 SNVs (single nucleotide variants) of the MLXIPL gene with dietary, anthropometric, and biochemical variables in Mexican Mestizo subjects. This is a cross-sectional study of 587 individuals. Genotyping was performed by allelic discrimination. In addition, liver and adipose tissue biopsies were obtained from a subgroup of 24 subjects to analyze the expression of the MLXIPL gene. An in silico test of the protein stability and allelic imbalance showed that rs17145750 and rs3812316 showed a high rate of joint heritability in a highly conserved area. The G allele of rs3812316 was associated with lower triglyceride levels (OR = −0.070 ± 0.027, p < 0.011, 95% CI = −0.124 to −0.016), the production of an unstable protein (ΔΔG −0.83 kcal/mol), and probably lower tissue mRNA levels. In addition, we found independent factors that also influence triglyceride levels, such as insulin resistance, HDL-c, and dietary protein intake in women. Our data showed that the association of rs3812316 on triglycerides was only observed in patients with an inadequate alpha-linolenic acid intake (1.97 ± 0.03 vs. 2.11 ± 0.01 log mg/dL, p < 0.001).

The rs9939609 Variant in FTO Increases the Risk of Hypercholesterolemia in Metabolically Healthy Subjects with Excess Weight.

INTRODUCTION: The fat mass and obesity-associated gene (FTO) is largely/primarily expressed in the hypothalamus. It plays a role in energy balance, regulation of food intake, and adipogenesis. According to metabolic phenotypes, studies have associated the FTO rs9939609 variant with body mass index (BMI), body fat mass, and dietary intake but not with serum lipids. This study aimed to analyze the association of the FTO rs9939609 variant with serum lipids in Mexican adults with different metabolic phenotypes. METHODS: We included 306 subjects aged 18-65 years, classified as normal weight or excess weight (EW) according to their BMI. EW included BMI from 25 to 39.9 kg/m2. Participants were classified into two metabolic phenotypes: metabolically healthy/metabolically unhealthy (MH/MUH). We use the homeostatic model assessment of insulin resistance and NCEP-ATP III cutoffs for glucose, triglycerides, high-density lipoprotein, and blood pressure. Subjects with ≥2 altered parameters were classified as MUH. The variant was determined by allelic discrimination with TaqMan® probes. RESULTS: In subjects with the A allele, significantly higher total cholesterol and low-density-lipoprotein cholesterol were found (p < 0.05). Furthermore, subjects with EW-MH and the AA or AT genotype had a significantly higher odds ratio for hypercholesterolemia (odds ratio 4.48, 95% confidence interval: 1.48-13.59, p = 0.008). CONCLUSION: The FTO rs9939609 variant may influence serum lipid concentrations, increasing the risk of hypercholesterolemia.

A comparison of opioid-containing anesthesia versus opioid-free anesthesia using the Cortínez-Sepúlveda model on differential cytokine responses in obese patients undergoing gastric bypass surgery: a randomized controlled trial.

BACKGROUND: Opioid anesthetic agents can modulate the impaired immune response in obese patients through mechanisms that involve the expression and release of cytokines. For this reason, anesthetic care for obese patients remains controversial. Therefore, the aim of the study was to compare the effect of opioid-containing anesthesia (OCA) vs opioid-free anesthesia (OFA) using the Cortínez-Sepúlveda model on IL-6, IL-1ß and TNF-α serum levels before and after surgery in obese patients undergoing bypass surgery. METHODS: This randomized cross-sectional study conducted among 40 unrelated obese adults was performed in the Civil Hospital of Guadalajara "Dr. Juan I. Menchaca". Before undergoing laparoscopic Roux-en-Y gastric bypass, patients were randomly assigned to two anesthesia groups: OCA (n = 20) or OFA (n = 20). Fentanyl was the opioid used in the OCA group. The Cortínez-Sepúlveda pharmacokinetic model was used to characterize the disposition of intravenous propofol for the target-controlled infusion technique in obese patients. Body mass was determined to the nearest 0.05 kg using a balance scale (Seca 703; Seca, Hamburg, Germany). Blood samples were taken before and immediately after surgery and cytokine concentrations were determined by ELISA. Pain was assessed using a numerical pain rating scale. Adverse effects were collected within the first 24 h after surgery. RESULTS: A total of 6 men and 34 women were included (37.9 ± 10.6 years). Pre-surgery IL-6 and TNF-α serum levels were not detected in study subjects. However, IL-1ß levels significantly decreased after surgery (49.58 pg/mL (18.50-112.20)-before surgery vs 13 pg/mL (5.43-22)-after surgery, p = 0.019). IL-6 concentrations were significantly higher in subjects who received OCA (with fentanyl) compared to subjects with OFA (224.5 pg/mL (186.3-262.8) vs 99.5 pg/mL (60.8-138.2), respectively, p < 0.001; adjusted by age, gender, and BMI). In addition, the use of opioids confers an increased risk for higher IL-6 levels in obese patients (OR = 2.95, 95% CI: 1.2-7.2, p = 0.010). A linear regression model showed that the operative time (in hours) of bypass surgery and anesthetic technique were positively correlated with IL-6 levels. CONCLUSION: Anesthesia with opioids correlated positively with IL-6 serum levels in obese patients undergoing bypass surgery. This finding could have clinical relevance when an appropriate anesthetic management plan is selected for bariatric surgical patients. TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov Identification Number: NCT04854252, date 22/04/2021.

Escherichia/Shigella, SCFAs, and Metabolic Pathways-The Triad That Orchestrates Intestinal Dysbiosis in Patients with Decompensated Alcoholic Cirrhosis from Western Mexico.

Gut microbiota undergoes profound alterations in alcohol cirrhosis. Microbiota-derived products, e.g., short chain fatty acids (SCFA), regulate the homeostasis of the gut-liver axis. The objective was to evaluate the composition and functions of the intestinal microbiota in patients with alcohol-decompensated cirrhosis. Fecal samples of 18 patients and 18 healthy controls (HC) were obtained. Microbial composition was characterized by 16S rRNA amplicon sequencing, SCFA quantification was performed by gas chromatography (GC), and metagenomic predictive profiles were analyzed by PICRUSt2. Gut microbiota in the cirrhosis group revealed a significant increase in the pathogenic/pathobionts genera Escherichia/Shigella and Prevotella, a decrease in beneficial bacteria, such as Blautia, Faecalibacterium, and a decreased α-diversity (p < 0.001) compared to HC. Fecal SCFA concentrations were significantly reduced in the cirrhosis group (p < 0.001). PICRUSt2 analysis indicated a decrease in acetyl-CoA fermentation to butyrate, as well as an increase in pathways related to antibiotics resistance, and aromatic amino acid biosynthesis. These metabolic pathways have been poorly described in the progression of alcohol-related decompensated cirrhosis. The gut microbiota of these patients possesses a pathogenic/inflammatory environment; therefore, future strategies to balance intestinal dysbiosis should be implemented. These findings are described for the first time in the population of western Mexico.