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Saudi Journal of Biological Sciences Oct 2023Obesity is a polygenic disorder which has become a global epidemic in recent years. Aim of the present study was to assess the theranostic potential of probiotics ( and...
Obesity is a polygenic disorder which has become a global epidemic in recent years. Aim of the present study was to assess the theranostic potential of probiotics ( and local herbs (fenugreek seeds, aloe vera) on the body weight, biochemical (liver and kidney functions) and histology of some internal organs (liver, kidney, ovary, small intestine) in obese rats. In present study, nanoemulsions of probiotics and local herbs were formulated by high energy method and characterized by FTIR and UV analysis. One hundred and sixty (1 6 0) female wistar rats were divided into sixteen groups. A high-fat diet was given to induce obesity in them. Obese rats were treated with different doses of probiotics, local herbs and their combination. Weekly body weight was monitored. Rats were dissected after fifteen weeks; blood and organs were harvested for biochemical analysis and histology. Results demonstrated a protective effect of nanoemulsion of probiotics and local herbs on the central vein, glomerulus, villi and normal ovulatory function of obese rats. Rats treated with a combination of probiotics and local herbs (fenugreek seeds, aloe vera) exhibited improved levels of bilirubin (4 mg/dl to15 mg/dl), AST from (110 U/L to 18 U/L) and ALT from (52 U/L to 10U/L). Similar renoprotective effects were recorded on the overall renal function tests (RFT). A combination of probiotics and local herbs in post treatment rats improved urea (63 mg/dl to 22 mg/dl) and creatinine (0.2 mg/dl to 0.8 mg/dl) levels. It was therefore evident that a combination of probiotics and local herbs has the potential to reverse the effects of obesity on the biochemical parameters and histological architecture of liver, kidney, small intestine and ovary. The overall results indicated that probiotics have positive effects of their own, but when combined with local herbs, they produced highly effective results in obese rats and therefore can be used as a complementary option in obese individuals.
PubMed: 37680978
DOI: 10.1016/j.sjbs.2023.103790 -
Nutrients Aug 2023Obesity is a metabolic state generated by the expansion of adipose tissue. Adipose tissue expansion depends on the interplay between hyperplasia and hypertrophy, and is... (Review)
Review
Obesity is a metabolic state generated by the expansion of adipose tissue. Adipose tissue expansion depends on the interplay between hyperplasia and hypertrophy, and is mainly regulated by a complex interaction between genetics and excess energy intake. However, the genetic regulation of adipose tissue expansion is yet to be fully understood. Obesity can be divided into common multifactorial/polygenic obesity and monogenic obesity, non-syndromic and syndromic. Several genes related to obesity were found through studies of monogenic non-syndromic obesity models. However, syndromic obesity, characterized by additional features other than obesity, suggesting a more global role of the mutant genes related to the syndrome and, thus, an additional peripheral influence on the development of obesity, were hardly studied to date in this regard. This review summarizes present knowledge regarding the hyperplasia and hypertrophy of adipocytes in common obesity. Additionally, we highlight the scarce research on syndromic obesity as a model for studying adipocyte hyperplasia and hypertrophy, focusing on Bardet-Biedl syndrome (BBS). BBS obesity involves central and peripheral mechanisms, with molecular and mechanistic alternation in adipocyte hyperplasia and hypertrophy. Thus, we argue that using syndromic obesity models, such as BBS, can further advance our knowledge regarding peripheral adipocyte regulation in obesity.
PubMed: 37571382
DOI: 10.3390/nu15153445 -
Temperature (Austin, Tex.) 2023We have previously identified predator odor as a potent stimulus activating thermogenesis in skeletal muscle in rats. As this may prove relevant for energy balance and...
We have previously identified predator odor as a potent stimulus activating thermogenesis in skeletal muscle in rats. As this may prove relevant for energy balance and weight loss, the current study investigated whether skeletal muscle thermogenesis was altered with negative energy balance, obesity propensity seen in association with low intrinsic aerobic fitness, and monogenic obesity. First, weight loss subsequent to 3 wk of 50% calorie restriction suppressed the muscle thermogenic response to predator odor. Next, we compared rats bred based on artificial selection for intrinsic aerobic fitness - high- and low-capacity runners (HCR, LCR) - that display robust leanness and obesity propensity, respectively. Aerobically fit HCR showed enhanced predator odor-induced muscle thermogenesis relative to the less-fit LCR. This contrasted with the profound monogenic obesity displayed by rats homozygous for a loss of function mutation in ( rats), which showed no discernable deficit in thermogenesis. Taken together, these data imply that body size or obesity are not associated with deficient muscle thermogenesis. Rather, the physiological phenotype associated with polygenic obesity propensity may encompass pleiotropic mechanisms in the thermogenic pathway. Adaptive thermogenesis associated with weight loss also likely alters muscle thermogenic mechanisms.
PubMed: 37554387
DOI: 10.1080/23328940.2023.2171669 -
Nature Genetics Sep 2023Binge eating disorder (BED) is the most common eating disorder, yet its genetic architecture remains largely unknown. Studying BED is challenging because it is often...
Binge eating disorder (BED) is the most common eating disorder, yet its genetic architecture remains largely unknown. Studying BED is challenging because it is often comorbid with obesity, a common and highly polygenic trait, and it is underdiagnosed in biobank data sets. To address this limitation, we apply a supervised machine-learning approach (using 822 cases of individuals diagnosed with BED) to estimate the probability of each individual having BED based on electronic medical records from the Million Veteran Program. We perform a genome-wide association study of individuals of African (n = 77,574) and European (n = 285,138) ancestry while controlling for body mass index to identify three independent loci near the HFE, MCHR2 and LRP11 genes and suggest APOE as a risk gene for BED. We identify shared heritability between BED and several neuropsychiatric traits, and implicate iron metabolism in the pathophysiology of BED. Overall, our findings provide insights into the genetics underlying BED and suggest directions for future translational research.
Topics: Humans; Binge-Eating Disorder; Genome-Wide Association Study; Obesity; Phenotype; Iron
PubMed: 37550530
DOI: 10.1038/s41588-023-01464-1 -
MedRxiv : the Preprint Server For... Jul 2023The study aimed to discover novel genetic loci for atrial fibrillation (AF), explore the shared genetic etiologies between AF and other cardiovascular and...
AIMS
The study aimed to discover novel genetic loci for atrial fibrillation (AF), explore the shared genetic etiologies between AF and other cardiovascular and cardiometabolic traits, and uncover AF pathogenesis using Mendelian randomization analysis.
METHODS AND RESULTS
We conducted a genome-wide association study meta-analysis including 109,787 AF cases and 1,165,920 controls of European ancestry and identified 215 loci, among which 91 were novel. We performed Genomic Structural Equation Modeling analysis between AF and four cardiovascular comorbidities (coronary artery disease, ischemic stroke, heart failure, and vneous thromboembolism) and found 189 loci shared across these diseases as well as a universal genetic locus shared by atherosclerotic outcomes (i.e., rs1537373 near ). Three genetic loci (rs10740129 near C, rs2370982 near , and rs9931494 near ) were associated with AF and cardiometabolic traits. A polygenic risk score derived from this genome-wide meta-analysis was associated with AF risk (odds ratio 2.36, 95% confidence interval 2.31-2.41 per standard deviation increase) in the UK biobank. This score, combined with age, sex, and basic clinical features, predicted AF risk (AUC 0.784, 95% CI 0.781-0.787) in Europeans. Phenome-wide association analysis of the polygenic risk score identified many AF-related comorbidities of the circulatory, endocrine, and respiratory systems. Phenome-wide and multi-omic Mendelian randomization analyses identified associations of blood lipids and pressure, diabetes, insomnia, obesity, short sleep, and smoking, 27 blood proteins, one gut microbe (), and 11 blood metabolites with risk to AF.
CONCLUSIONS
This genome-wide association study and trans-omic Mendelian randomization analysis provides insights into disease risk prediction, pathophysiology and downstream sequelae.
PubMed: 37546828
DOI: 10.1101/2023.07.20.23292938 -
Genetics of Pulmonary Pressure and Right Ventricle Stress Identify Diabetes as a Causal Risk Factor.Journal of the American Heart... Aug 2023Background Epidemiologic studies have identified risk factors associated with pulmonary hypertension and right heart failure, but causative drivers of pulmonary...
Background Epidemiologic studies have identified risk factors associated with pulmonary hypertension and right heart failure, but causative drivers of pulmonary hypertension and right heart adaptation are not well known. We sought to leverage unbiased genetic approaches to determine clinical conditions that share genetic architecture with pulmonary pressure and right ventricular dysfunction. Methods and Results We leveraged Vanderbilt University's deidentified electronic health records and DNA biobank to identify 14 861 subjects of European ancestry who underwent at least 1 echocardiogram with available estimates of pulmonary pressure and right ventricular function. Analyses of the study were performed between 2020 and 2022. The final analytical sample included 14 861 participants (mean [SD] age, 63 [15] years and mean [SD] body mass index, 29 [7] kg/m). An unbiased phenome-wide association study identified diabetes as the most statistically significant clinical , () code associated with polygenic risk for increased pulmonary pressure. We validated this finding further by finding significant associations between genetic risk for diabetes and a related condition, obesity, with pulmonary pressure estimate. We then used 2-sample univariable Mendelian randomization and multivariable Mendelian randomization to show that diabetes, but not obesity, was independently associated with genetic risk for increased pulmonary pressure and decreased right ventricle load stress. Conclusions Our findings show that genetic risk for diabetes is the only significant independent causative driver of genetic risk for increased pulmonary pressure and decreased right ventricle load stress. These findings suggest that therapies targeting genetic risk for diabetes may also potentially be beneficial in treating pulmonary hypertension and right heart dysfunction.
Topics: Humans; Middle Aged; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Heart Ventricles; Hypertension, Pulmonary; Obesity; Risk Factors; Aged
PubMed: 37522172
DOI: 10.1161/JAHA.122.029190 -
International Journal of Molecular... Jul 2023Hundreds of genetic variants for body mass index (BMI) have been identified from numerous genome-wide association studies (GWAS) in different ethnicities. In this study,...
Hundreds of genetic variants for body mass index (BMI) have been identified from numerous genome-wide association studies (GWAS) in different ethnicities. In this study, we aimed to develop a polygenic risk score (PRS) for BMI for predicting susceptibility to obesity and related traits in the Korean population. For this purpose, we obtained base data resulting from a GWAS on BMI using 57,110 HEXA study subjects from the Korean Genome and Epidemiology Study (KoGES). Subsequently, we calculated PRSs in 13,504 target subjects from the KARE and CAVAS studies of KoGES using the PRSice-2 software. The best-fit PRS for BMI (PRS) comprising 53,341 SNPs was selected at a -value threshold of 0.064, at which the model fit had the greatest score. The PRS was tested for its association with obesity-related quantitative traits and diseases in the target dataset. Linear regression analyses demonstrated significant associations of PRS with BMI, blood pressure, and lipid traits. Logistic regression analyses revealed significant associations of PRS with obesity, hypertension, and hypo-HDL cholesterolemia. We observed about 2-fold, 1.1-fold, and 1.2-fold risk for obesity, hypertension, and hypo-HDL cholesterolemia, respectively, in the highest-risk group in comparison to the lowest-risk group of PRS in the test population. We further detected approximately 26.0%, 2.8%, and 3.9% differences in prevalence between the highest and lowest risk groups for obesity, hypertension, and hypo-HDL cholesterolemia, respectively. To predict the incidence of obesity and related diseases, we applied PRS to the 16-year follow-up data of the KARE study. Kaplan-Meier survival analysis showed that the higher the PRS, the higher the incidence of dyslipidemia and hypo-HDL cholesterolemia. Taken together, this study demonstrated that a PRS developed for BMI may be a valuable indicator to assess the risk of obesity and related diseases in the Korean population.
Topics: Humans; Body Mass Index; Genetic Predisposition to Disease; Genome-Wide Association Study; Obesity; Risk Factors; Hypertension; Republic of Korea; Polymorphism, Single Nucleotide
PubMed: 37511320
DOI: 10.3390/ijms241411560 -
Diagnostics (Basel, Switzerland) Jul 2023Atherogenic dyslipidemia plays a critical role in the development of metabolic syndrome (MetS), being one of its major components, along with central obesity, insulin... (Review)
Review
Atherogenic dyslipidemia plays a critical role in the development of metabolic syndrome (MetS), being one of its major components, along with central obesity, insulin resistance, and hypertension. In recent years, the development of molecular genetics techniques and extended analysis at the genome or exome level has led to important progress in the identification of genetic factors (heritability) involved in lipid metabolism disorders associated with MetS. In this review, we have proposed to present the current knowledge related to the genetic etiology of atherogenic dyslipidemia, but also possible challenges for future studies. Data from the literature provided by candidate gene-based association studies or extended studies, such as genome-wide association studies (GWAS) and whole exome sequencing (WES,) have revealed that atherogenic dyslipidemia presents a marked genetic heterogeneity (monogenic or complex, multifactorial). Despite sustained efforts, many of the genetic factors still remain unidentified (missing heritability). In the future, the identification of new genes and the molecular mechanisms by which they intervene in lipid disorders will allow the development of innovative therapies that act on specific targets. In addition, the use of polygenic risk scores (PRS) or specific biomarkers to identify individuals at increased risk of atherogenic dyslipidemia and/or other components of MetS will allow effective preventive measures and personalized therapy.
PubMed: 37510094
DOI: 10.3390/diagnostics13142348 -
Open Respiratory Archives 2023The circadian rhythm of sleep occurs in a cyclical 24-h pattern that is adjusted by the influence of several main synchronizers or "zeitgebers". The most powerful... (Review)
Review
The circadian rhythm of sleep occurs in a cyclical 24-h pattern that is adjusted by the influence of several main synchronizers or "zeitgebers". The most powerful synchronizer is the light-dark alternation, but also, socio-economic factors play a role, such as social and work relationships. Circadian rhythm regulation plays a crucial role in human health. This disruption of circadian rhythm can lead to increased incidence of diseases: diabetes, obesity, cancer, neurodegenerative diseases, increased risk of cardiovascular disease and stroke. Polygenic variations and environmental factors influence the circadian rhythm of each person. This is known as chronotype, which manifests itself as the degree of morning of evening preferences of each individual. There are indications to establish an association between individual chronotype preferences and the behavior of respiratory diseases.
PubMed: 37497245
DOI: 10.1016/j.opresp.2022.100228 -
The Lancet Regional Health. Southeast... Jul 2023A machine-learning approach identified five subgroups of diabetes in Europeans which included severe autoimmune diabetes (SAID), severe insulin-deficient diabetes...
BACKGROUND
A machine-learning approach identified five subgroups of diabetes in Europeans which included severe autoimmune diabetes (SAID), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD) with partially distinct genetic aetiologies. We previously validated four of the non-autoimmune subgroups in people with young-onset type 2 diabetes (T2D) from the Indian WellGen study. Here, we aimed to apply European-derived centroids and genetic risk scores (GRSs) to the unselected (for age) WellGen to test their applicability and investigate the genetic aetiology of the Indian T2D subgroups.
METHODS
We applied European derived centroids and GRSs to T2D participants of Indian ancestry (WellGen, n = 2217, 821 genotyped) and compared them with normal glucose tolerant controls (Pune Maternal Nutrition Study, n = 461).
FINDINGS
SIDD was the predominant subgroup followed by MOD, whereas SIRD and MARD were less frequent. Weighted-GRS for T2D, obesity and lipid-related traits associated with T2D. We replicated some of the previous associations of GRS for T2D, insulin secretion, and BMI with SIDD and MOD. Unique to Indian subgroups was the association of GRS for (a) proinsulin with MOD and MARD, (b) liver-lipids with SIDD, SIRD and MOD, and (c) opposite effect of beta-cell GRS with SIDD and MARD, obesity GRS with MARD compared to Europeans. Genetic variants of fucosyltransferases were associated with T2D and MOD in Indians but not Europeans.
INTERPRETATION
The similarities emphasise the applicability of some of the European-derived GRSs to T2D and its subgroups in India while the differences highlight the need for large-scale studies to identify aetiologies in diverse ancestries. The data provide robust evidence for genetically distinct aetiologies for the T2D subgroups and at least partly mirror those seen in Europeans.
FUNDING
Vetenskapsrådet, Diabetes Wellness, and Hjärt-Lungfonden (Sweden), DST (India), Wellcome Trust, Crafoord Foundation and Albert Påhlsson Foundation.
PubMed: 37492423
DOI: 10.1016/j.lansea.2023.100182