Search Results (91)

Deposition of intramuscular fat (IM), also known as marbling, is the deciding factor of beef quality grade in the U.S. Defining molecular mechanisms underlying the differential deposition of adipose tissue in distinct anatomical areas in beef cattle is key to the development of strategies for marbling enhancement while limiting the accumulation of excessive subcutaneous adipose tissue (SAT). The objective of this exploratory study was to define the IM and SAT transcriptional heterogeneity at the whole tissue and single-nuclei levels in beef steers. Longissimus dorsi muscle samples (9–11th rib) were collected from two finished beef steers at harvest to dissect matched IM and adjacent SAT (backfat). Total RNA from IM and SAT was isolated and sequenced in an Illumina NovaSeq 6000. Nuclei from the same samples were isolated by dounce homogenization, libraries generated with 10× Genomics, and sequenced in an Illumina NovaSeq 6000, followed by analysis via Cell Ranger pipeline and Seurat in RStudio (v4.3.2) By the expression of signature marker genes, single-nuclei RNA sequencing (snRNAseq) analysis identified mature adipocytes (AD; ADIPOQ, LEP), adipose stromal and progenitor cells (ASPC; PDGFRA), endothelial cells (EC; VWF, PECAM1), smooth muscle cells (SMC; NOTCH3, MYL9) and immune cells (IMC; CD163, MRC1). We detected six cell clusters in SAT and nine in IM. Across IM and SAT, AD was the most abundant cell type, followed by ASPC, SMC, and IMC. In SAT, AD made up 50% of the cellular population, followed by ASPC (31%), EC (14%), IMC (1%), and SMC (4%). In IM depot, AD made up 23% of the cellular population, followed by ASPC at 19% of the population, EC at 28%, IMC at 7% and SMC at 12%. The abundance of ASPC and AD was lower in IM vs. SAT, while IMC was increased, suggesting a potential involvement of immune cells on IM deposition. Accordingly, both bulk RNAseq and snRNAseq analyses identified activated pathways of inflammation and metabolic function in IM. These results demonstrate distinct transcriptional cellular heterogeneity between SAT and IM depots in beef steers, which may underly the mechanisms by which fat deposits in each depot. The identification of depot-specific cell populations in IM and SAT via snRNAseq analysis has the potential to reveal target genes for the modulation of fat deposition in beef cattle. Full article

Metabolic syndrome (MetS), a significant global health concern, is characterized as a cluster of metabolic abnormalities that elevate the risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Adiponectin, an adipokine secreted by adipose tissue, plays a crucial role in regulating glucose and lipid homeostasis while exhibiting protective effects against vascular alterations. Single-nucleotide variants (SNVs) in the ADIPOQ gene have significantly affected circulating adiponectin levels and metabolic parameters. This narrative review examines current evidence on the relationship between adiponectin, ADIPOQ gene variants, and metabolic syndrome. The findings indicate that lower adiponectin levels are associated with an increased risk of metabolic syndrome components, including elevated triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), and fasting glucose levels. In conclusion, adiponectin emerges as a key regulator of metabolic homeostasis, with SNVs in the ADIPOQ gene correlating with the development of metabolic-related complications. Full article

Background/Objectives: Disruptions in adipose tissue dynamics contribute to obesity-related metabolic disorders, emphasizing the need for targeted therapies focusing on adipose tissue cells, including progenitor cells and adipocytes. Peroxisome proliferator-activated receptor gamma (PPARG) ligands are potent insulin sensitizers used in type 2 diabetes treatment. This study investigated the effects of rosiglitazone, a PPARG agonist, and betulinic acid, a PPARG antagonist, on adipogenesis and apoptosis in 3T3-L1 pre-adipocytes. Method: 3T3-L1 pre-adipocytes were treated with rosiglitazone or betulinic acid during adipogenic differentiation. Lipid droplet formation was used to evaluate adipogenesis. Cell growth and cell death were assessed using the resazurin-based cell viability assay, trypan blue exclusion assay, LDH assay, and Annexin V/PI staining. Quantitative PCR was conducted to examine the expression of genes associated with adipogenesis and apoptosis. Results: Betulinic acid reduced adipogenesis only when administered daily for eight days. Rosiglitazone did not alter the overall lipid quantity; however, it promoted a shift toward fewer but larger lipid droplets. Both compounds increased Adipoq and Cfd expression, and betulinic acid also elevated Fabp4. Rosiglitazone induced stronger cell aggregation. Despite increased cell death, overall viability was maintained. Apoptotic cell death was enhanced by both compounds and confirmed via Annexin V/PI staining and flow cytometry, accompanied by downregulation of Ccnd1 and Bcl2. Additionally, rosiglitazone markedly increased the expression of Cebpa, a key regulator that can modulate lipid droplet formation and the balance between cell growth and death. Conclusions: Rosiglitazone and betulinic acid differentially modulate adipogenesis and apoptosis in 3T3-L1 cells, revealing a complex interplay between lipid accumulation and programmed cell death. Together, the findings underscore the potential of dual PPARG-targeting approaches for metabolic disease interventions. Full article

Insulin resistance (IR) is a metabolic disorder characterized by an impaired response to insulin. This condition is associated with excess adiposity and metabolic inflammation, contributing to an increased risk for related chronic diseases. Single-nucleotide polymorphisms (SNPs) can affect genes related to metabolic pathways which are related to IR and the individual response to nutrients and dietary patterns, affecting metabolic inflammation and insulin sensitivity. This narrative review explores the current evidence on interactions between genetic variants and dietary factors, specifically their effects in modulating IR and metabolic inflammation. A comprehensive search of the literature was conducted in PubMed, Google Scholar, and Web of Science, and a total of 95 articles were reviewed. The key findings reveal that SNPs in the TCF7L2, ADIPOQ, and TNF genes significantly influence metabolic responses and modulate the effects of the Mediterranean diet on biomarkers of inflammation and IR. Genotype-dependent variations in IR and inflammation biomarkers were observed in the response to different diets for SNPs in the TCF7L2, ADIPOQ, and TNF genes. Additionally, polygenic risk scores (PRSs) can also predict the response to the intake of nutrients and specific diets, and offer a promising tool for assessing genetic predisposition to IR. This review underscores the pivotal role of an individual’s genetic background in the effects of their nutrient intake and in the responses to dietetic interventions, thereby laying the foundation for personalized and effective nutritional strategies tailored to each individual’s necessity in mitigating IR and its associated risk factors for chronic diseases. Full article

Background: Ectopic fat deposition refers to lipid accumulation that affects metabolic function and tissue characteristics. Japanese Black cattle are distinguished by their high intramuscular fat content, which contributes to their distinctive character. However, the genetic mechanisms underlying these traits remain unclear. This study compared gene expression patterns in different muscle regions to identify genes associated with intramuscular fat accumulation. First, we conducted RNA sequencing to analyze differences in gene expression profiles among the sternocleidomastoid, pectoralis minor, and pectoralis major muscles. In addition, single-cell nuclear RNA sequencing was conducted to investigate the cellular composition of these muscle tissues. Results: Distinct gene expression patterns were observed among the different muscles. In the pectoralis, which contains a high proportion of intramuscular fat, adipocyte-related genes such as FABP4, SCD, and ADIPOQ were highly expressed. In addition, lipases such as PNPLA2, LPL, MGLL, and LIPE were predominantly expressed in intramuscular fat, whereas PLA2G12A, PLD3, and ALOX15 were specifically expressed in myofibers. Moreover, a subclass of fibro–adipogenic progenitor cells that differentiate into intramuscular adipocytes was found to express genes related to microenvironment formation, including ICAM1, TGFBRs, and members of the COL4A family. Conclusions: This study provides novel insight into the genetic regulation of intramuscular fat accumulation. It improves our understanding of the molecular mechanisms underlying their distinctive meat characteristics. Full article

In mammals, exposure to low temperatures induces white adipose tissue (WAT) browning and alters lipid metabolism to promote thermogenesis, thereby maintaining body temperature. However, this response varies across different adipose depots. In this study, Hezuo pigs were exposed to either room temperature (23 ± 2 °C) or low temperature (−15 ± 2 °C) for periods of 12 h, 24 h, 48 h, 5 d, 10 d, and 15 d. Inguinal fat (IF) and perirenal fat (PF) were collected and analyzed using hematoxylin and eosin (HE) staining, transmission electron microscopy, RT-qPCR, and RNA-seq. Following cryoexposure, our results demonstrated a significant increase in adipocyte number and a corresponding decrease in cross-sectional area in both IF and PF groups from 24 h to 10 d. While adipocyte numbers were elevated at 12 h and 15 d, these changes were not statistically significant. Moreover, lipid droplets and mitochondria were more abundant, and the mRNA expression levels of thermogenic genes UCP3 and PGC-1α were significantly higher compared to the control group during the 24 h-10 d cold exposure period. No significant changes were observed in the other groups. RNA-seq data indicated that the lipid metabolism of IF and PF peaked on day 5 of low-temperature treatment. In IF tissue, lipid metabolism is mainly regulated by genes such as FABP4, WNT10B, PCK1, PLIN1, LEPR, and ADIPOQ. These genes are involved in the classical lipid metabolism pathway and provide energy for cold adaptation. In contrast, in PF tissue, genes like ATP5F1A, ATP5PO, SDHB, NDUFS8, SDHA, and COX5A play roles within the neurodegenerative disease pathway, and PF tissue has a positive impact on the process related to degenerative diseases. Further investigation is needed to clarify the functions of these candidate genes in lipid metabolism in Hezuo pigs and to explore the genetic mechanisms underlying the cold-resistance traits in local pig populations. Full article

Gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) are public health concerns worldwide. These two diseases share the same pathophysiological and genetic similarities. This study aimed to investigate the T2DM known single nucleotide polymorphisms (SNPs) of the adiponectin C1Q and collagen domain containing (ADIPOQ), cyclin-dependent kinase inhibitor 2A and 2B (CDKN2A/2B), and signal sequence receptor subunit 1 (SSR1) genes in a cohort of Romanian GDM pregnant women and perinatal outcomes. DNA was isolated from the peripheral blood of 213 pregnant women with (n = 71) or without (n = 142) GDM. Afterward, ADIPOQ (rs266729), CDKN2A/2B (rs10811661), and SSR1 (rs9505118) gene polymorphisms were genotyped using TaqMan Real-Time PCR analysis. Women with GDM had a higher pre-pregnancy body mass index (BMI) (p < 0.0001), higher BMI (p < 0.0001), higher insulin resistance homeostatic model assessment (IR-HOMA) (p = 0.0002), higher insulin levels (p = 0.003), and lower adiponectin levels (p = 0.004) at birth compared to pregnant women with normoglycemia. GDM pregnant women had gestational hypertension (GH) more frequently during pregnancy (p < 0.0001), perineal lacerations more frequently during vaginal birth (p = 0.03), and more macrosomic newborns (p < 0.0001) than pregnant women from the control group. We did not find an association under any model (allelic, genotypic, dominant, or recessive) of ADIPOQ rs266729, CDKN2A/2B rs10811661, and SSR1 rs9505118 polymorphisms and GDM. In correlation analysis, we found a weak positive correlation (r = 0.24) between the dominant model GG + CG vs. CC of rs266729 and labor induction failure. In the dominant model TT vs. CC + CT of rs10811661, we found a weak negative correlation between this model and perineal lacerations. Our results suggest that the ADIPOQ rs266729, the CDKN2A/2B rs10811661, and the SSR1 rs9505118 gene polymorphisms are not associated with GDM in a cohort of Romanian pregnant women. Full article

Background: Gestational diabetes mellitus (GDM) is linked to higher newborn weight and an increased risk of macrosomia. The newborn single-nucleotide polymorphism (SNP) of the ADIPOQ gene rs266729 is linked to a higher birth weight of the offspring of healthy pregnant women. Objectives: This study aims to evaluate the relationship between newborn ADIPOQ rs266729 polymorphism, cord blood adiponectin, maternal glycemic and lipid metabolism, and maternal adiponectin levels at 24 to 28 weeks of gestation (WG) and at birth and its impact on newborn weight in a cohort of GDM mothers. Materials and methods: This study involved 71 women diagnosed with GDM and 142 control pregnant women. The ADIPOQ (rs266729) gene polymorphisms were genotyped using TaqMan real-time PCR analysis. Maternal and cord blood adiponectin levels were measured using human total adiponectin ELISA kits. We performed a Pearson correlation analysis to identify significant correlations between maternal metabolic parameters and adiponectin levels at 24–28 WG and birth and the weight of newborns. A logistic regression analysis was also conducted to identify potential macrosomia predictors. Results: We found no significant differences in the distribution of the allele (C, G) (p = 0.82) and genotype (CC, CG, GG) (p = 0.46) of APIPOQ rs266729 among normoponderal and macrosomic newborns from the GDM mothers group. Maternal fasting glucose at 24–28 WG was higher in the GDM mothers who gave birth to macrosomic newborns (106 ± 17 vs. 93 ± 10 mg/dL, p < 0.0001). Adiponectin levels in the cord blood of newborns from mothers with GDM were lower than those in newborns from control mothers (p < 0.0001). In correlation analysis, we identified a weak positive correlation between the newborn weight of GDM mothers and cord blood adiponectin (r = 0.262), maternal fasting glucose level at 24–28 WG (r = 0.288), and maternal adiponectin level at birth (0.334). Multivariate logistic regression, after adjusting for confounders, revealed that maternal fasting glucose levels at 24–28 WG had an OR of 11.59, and cord blood adiponectin levels had an OR of 30.31 for macrosomia. Conclusions: The preliminary findings of our pilot study suggest that in the gestational diabetes mellitus group, the ADIPOQ rs266729 polymorphism in newborns is not associated with a higher birth weight, maternal fasting glucose levels between 24 and 28 WG were a predictor for macrosomia, and cord blood adiponectin levels were lower than those from control mothers. Further large-scale studies are needed to confirm our findings. Full article

Intramuscular fat (IMF) content plays a crucial role in determining pork quality. Recent studies have highlighted transcriptional mechanisms controlling adipogenesis in porcine IMF. However, the changes in chromatin accessibility during adipogenic differentiation are still not well understood. In this study, we performed the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and transcriptome sequencing (RNA-Seq) analyses on porcine intramuscular preadipocytes to explore their adipogenic differentiation into mature adipocytes. We identified a total of 56,374 differentially accessible chromatin peaks and 4226 differentially expressed genes at day 0 and day 4 during adipogenic differentiation. A combined analysis of the ATAC-seq and RNA-seq data revealed that 1750 genes exhibited both differential chromatin accessibility and differential RNA expression during this process, including selenium-binding protein 1 (SELENBP1), PLIN1, ADIPOQ, and FASN. Furthermore, we found that vitamin D receptor (VDR) could bind to the promoter region of the SELENBP1 gene, activate SELENBP1 transcription, and ultimately promote lipid accumulation during adipogenic differentiation. This study provides a detailed overview of chromatin accessibility and gene expression changes during the adipogenic differentiation of porcine intramuscular preadipocytes. Moreover, we propose a novel regulatory mechanism involving the VDR–SELENBP1 signaling axis in adipogenic differentiation. Full article

Iron overload is a common complication in various chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD). Lipid and bile acid metabolism disorders are regarded as crucial hallmarks of NAFLD. However, effects of iron accumulation on lipid and bile acid metabolism are not well understood. Ferulic acid (FA) can chelate iron and regulate lipid and bile acid metabolism, but its potential to alleviate lipid and bile acid metabolism disorders caused by iron overload remains unclear. Here, in vitro experiments, iron overload induced oxidative stress, apoptosis, genomic instability, and lipid deposition in AML12 cells. FA reduced lipid and bile acid synthesis while increasing fatty acid β-oxidation and bile acid export, as indicated by increased mRNA expression of PPARα, Acox1, Adipoq, Bsep, and Shp, and decreased mRNA expression of Fasn, Acc, and Cyp7a1. In vivo experiments, FA mitigated liver injury in mice caused by iron overload, as indicated by reduced AST and ALT activities, and decreased iron levels in both serum and liver. RNA-seq results showed that differentially expressed genes were enriched in biological processes related to lipid metabolism, lipid biosynthesis, lipid storage, and transport. Furthermore, FA decreased cholesterol and bile acid contents, downregulated lipogenesis protein FASN, and bile acid synthesis protein CYP7A1. In conclusion, FA can protect the liver from lipid and bile acid metabolism disorders caused by iron overload by targeting FASN and CYP7A1. Consequently, FA, as a dietary supplement, can potentially prevent and treat chronic liver diseases related to iron overload by regulating lipid and bile acid metabolism. Full article

Background: Obesity is a pressing public health issue in Malaysia, involving not only excess weight but also complex metabolic and physiological changes. Addressing these complexities requires comprehensive strategies, including understanding the population-level differences in obesity susceptibility. This review aims to compile the genetic variants studied among Malaysians and emphasize their implications for obesity risk. Methods: Relevant articles published up to March 2024 were extracted from the Scopus, PubMed, and ScienceDirect databases. The review process was conducted in accordance with the PRISMA-ScR guidelines. From an initial pool of 579 articles, 35 of these were selected for the final review. Results: The identified gene variants, including LEPR (K656N), LEP (G2548A—Indian only), ADIPOQ (rs17366568), UCP2 (45bp-I/D), ADRB3 (rs4994), MC3R (rs3827103), PPARγ (pro12Ala—Malay only), IL1RA (intron 2 VNTR), NFKB1 (rs28362491), and FADS1 (rs174547—Indian only), showed significant associations with obesity as measured by the respective studies. Conclusions: Overall, more intensive genetic research is needed, starting with population-based profiling of genetic data on obesity, including among children. Sociocultural contexts and environmental factors influence variations in genetic elements, highlighting the need for targeted interventions to mitigate the impacts of obesity in the population. Full article

Genetic epidemiological studies have shown that numerous genetic variants cumulatively increase obesity risk. Although genetically predisposed individuals are more prone to developing obesity, it has been shown that physical activity can modify the genetic predisposition to obesity. Therefore, genetic data obtained from earlier studies, including 30 polymorphisms located in 18 genes, were analyzed using novel methods such as the total genetic score and Biofilter 2.4 software to combine genotypic and phenotypic information for nine obesity-related traits measured before and after the realization of the 12-week training program. The results revealed six genes whose genotypes were most important for post-training changes—LEP, LEPR, ADIPOQ, ADRA2A, ADRB3, and DRD2. Five noteworthy pairwise interactions, LEP × LEPR, ADRB2 × ADRB3, ADRA2A × ADRB3, ADRA2A × ADRB2, ADRA2A × DRD2, and three specific interactions demonstrating significant associations with key parameters crucial for health, total cholesterol (TC), high-density lipoprotein (HDL), and fat-free mass (FFM), were also identified. The molecular basis of training adaptation described in this study would have an enormous impact on the individualization of training programs, which, designed according to a given person’s genetic profile, will be effective and safe intervention strategies for preventing obesity and improving health. Full article

ADIPOQ plays a crucial role in regulating the reproductive system, but there are few reports on the effects of ADIPOQ on ovarian in dairy cows. Previous studies have verified the presence of a 67-bp mutation in the promoter region of the ADIPOQ gene. Hence, we employed ovarian tissues (n = 2111) and blood samples (n = 108) from Chinese Holstein cows as experimental samples to examine the association between ADIPOQ promoter variants and ovarian traits. We extracted DNA from these samples and conducted genetic typing identification on each sample using advanced techniques like PCR and agarose gel electrophoresis. Consequently, the DD, ID, and II genotypes were discovered. and it has been observed that the mutation frequency of this locus is low in the Chinese Holstein cow. Importantly, the correlational analysis unveiled a significant relationship (p < 0.05) between the weight of ovaries in late estrus and the width of ovaries during the estrus interval with the mutation. Result of the RT-PCR revealed that the ID genotype partially diminished the expression of the ADIPOQ gene. The results of this study suggest that the identified variable duplication could serve as a potential genetic marker for enhancing the ovarian traits of Chinese Holstein cows. Full article

Background and Objectives: Recent studies have focused on the association between the risk of diabetic retinopathy (DR) and the rs1501299 and rs2241766 polymorphisms of the ADIPOQ gene; however, their results remain inconclusive. Thus, a systematic review and meta-analysis were carried out to clarify the role of these polymorphisms in the development of DR. Materials and Methods: A systematic search of electronic databases (PubMed, Scopus, and Cochrane Library) was conducted until 25 June 2024, and a reference list of relevant articles was collected, which explored the association between the rs1501299 and rs2241766 polymorphisms of the ADIPOQ gene and the risk of DR. The pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated via random-effects model, and the meta-analysis was implemented by using Review Manager 5.4. Results: In total, 6 out of 182 studies, with 1888 cases (DR) and 2285 controls (without DR), were included in the meta-analysis. A statistically significant association between the rs1501299 polymorphism and the DR risk was recorded in G vs. T in the overall analysis (OR = 0.84, 95% CI = 0.72–0.99, p = <0.05, I² = 23%, n = 5 studies). Additionally, the summary results in the subgroup analysis according to the control type were as follows: the DR versus diabetes mellitus (DM) control type revealed a statistically significant association in G vs. T: OR = 0.81, 95% CI = 0.67–0.97, p = <0.05, I² = 27%, n = 4 studies; GG vs. GT: OR = 0.72, 95% CI = 0.53–0.98, p = <0.05, I² = 49%, n = 4 studies; GG vs. (GT + TT): OR = 0.73, 95% CI = 0.55–0.96, p = <0.05, I² = 44%, n = 4 studies. No significant association was observed between the rs2241766 polymorphism and the DR risk. Conclusions: The current meta-analysis supports the association between the rs1501299 polymorphism of the ADIPOQ gene and the DR risk in patients with DM. Full article

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