Obese Model Research Articles

Daily Orange Consumption Reduces Hepatic Steatosis Prevalence in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: Exploratory Outcomes of a Randomized Clinical Trial.

Background: Consumption of flavonoid-rich orange juice has been shown to reduce adiposity and liver steatosis in murine models of diet-induced obesity. However, little is known about the effects of whole orange intake, independent of body weight changes, on liver function and steatosis in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). The goal is to understand the direct impact of orange consumption on metabolic health. Methods: Sixty-two men and women aged 30-65 with MASLD (Controlled Attenuation Parameter, (CAP) > 275 dB/m) were randomly assigned to consume either 400 g of whole oranges or non-citrus fruits daily for 4 weeks. Baseline evaluations included medical assessments, blood tests, and body composition. Liver health was assessed using transient elastography (FibroScan®) for steatosis and fibrosis, conducted by blinded personnel. This clinical trial was registered at ClinicalTrials.gov (NCT05558592). Results: After 4 weeks of orange supplementation, liver steatosis decreased in the treatment group, with 70.9% showing steatosis compared to 100% in controls (p < 0.004), indicating a 30% reduction in liver disease prevalence. There were no significant changes in fibrosis or plasma liver enzymes, though plasma gamma glutaril transferase (GGT) levels decreased significantly. Body weight, waist circumference, body composition, lipid profile, fasting glucose, insulin, and C-reactive protein levels remained unchanged. Dietary analysis revealed no change in caloric intake, but vitamins C, A, thiamine, and riboflavin increased in the orange group. Conclusions: Our findings suggest that phytochemical-rich foods, especially whole fruits like oranges, may enhance liver function as an adjunct treatment for MASLD. The notable reduction in liver steatosis prevalence occurred independently of body weight changes. Further studies are needed to investigate the long-term effects of orange supplementation on steatosis and fibrosis progression and to identify the specific bioactive compounds and mechanisms involved.

Efficacy and mechanism of Schisandra chinensis active component Gomisin A on diabetic skin wound healing: network pharmacology and in vivo experimental validation

Ethnopharmacological relevanceSchisandra chinensis (Turcz.) Baill., a common traditional Chinese herbal medicine, has been used for the treatment of diabetes mellitus and its complications. However, the major active component for treating diabetic foot ulcers, a serious complication of diabetes mellitus, was unclear. This study aimed to predict the treatment effect of the active components in Schisandra chinensis against diabetic skin wound using network pharmacology and to confirm the underlying mechanism using a diabetic skin wound model in vivo. Aim of the studyTo study the effects and underlying mechanisms of Schisandra chinensis and its main component Gomisin A on diabetic skin wound healing by network pharmacology and high-fat diet (HFD)-induced obese mice model in vivo. Materials and methodsTo determine the effectiveness of Schisandra chinensis on diabetic skin wound, network pharmacology was first used. Components of Schisandra chinensis were obtained from the Traditional Chinese Medicine Systems Pharmacology database. The active components were further verified through absorption, distribution, metabolism and excretion. The potential targets of the active components were identified from the Traditional Chinese Medicine Systems Pharmacology, SwissTargetPrediction, TargetNet, and the Comparative Toxicogenomics Database. Targets related to diabetic skin wound were collected from the GeneCards, OMIM, DisGeNET, and PharmGKB databases. The interaction network formed by the intersection of the two datasets was analyzed using Gephi. Network-based proximity was used to predict the network distance between the active components of Schisandra chinensis and diabetic skin wound. Gomisin A was found to have the lowest Z-score and was administered either orally or via topical injection to HFD-induced obese mice daily until the wounds healed, and its effects on skin wound healing were evaluated. ResultsOnly five active ingredients of Schisandra chinensis were screened in our system: Gomisin A, Longikaurin A, Deoxyharringtonine, Wuweizisu C, and Interiotherin B, which can regulate biological processes related to diabetic skin wound, including positive regulation of phosphorous metabolic process, positive regulation of cell migration, and response to wounding. Network proximity analysis found that Gomisin A has the closest distance-based Z-score among the diabetic skin wound modules and drug targets in the human protein-protein interaction network. The HFD-induced obese mice model further revealed that Gomisin A accelerated skin wound healing by increasing insulin sensitivity and decreasing the advanced glycation end-products mediated toll-like receptor 4 (TLR4)-p38 MAPK-IL6 inflammation signaling pathway. ConclusionsThe network pharmacology and in vivo studies indicated that Gomisin A from Schisandra chinensis played a crucial role in improving diabetic skin wound healing.

Enteric glial NLRP3 inflammasome contributes to gut mucosal barrier alterations in a mouse model of diet-induced obesity.

In the present study, we investigated the involvement of NLRP3 inflammasome in the intestinal epithelial barrier (IEB) changes associated with obesity, and its role in the interplay between enteric glia and intestinal epithelial cells (IECs). Wild-type C57BL/6J and NLRP3-KO (-/-) mice were fed with high-fat diet (HFD) or standard diet for 8 weeks. Colonic IEB integrity and inflammasome activation were assessed. Immunolocalization of colonic mucosal GFAP- and NLRP3-positive cells along with invitro coculture experiments with enteric glial cells (EGCs) and IECs allowed to investigate the potential link between altered IEB, enteric gliosis, and NLRP3 activation. HFD mice showed increased body weight, altered IEB integrity, increased GFAP-positive glial cells, and NLRP3 inflammasome hyperactivation. HFD-NLRP3-/- mice showed a lower increase in body weight, an improvement in IEB integrity and an absence of enteric gliosis. Coculture experiments showed that palmitate and lipopolysaccharide contribute to IEB damage and promote enteric gliosis with consequent hyperactivation of enteric glial NLRP3/caspase-1/IL-1β signaling. Enteric glial-derived IL-1β release exacerbates the IEB alterations. Such an effect was abrogated upon incubation with anakinra (IL-1β receptor antagonist) and with conditioned medium derived from silenced-NLRP3 glial cells. HFD intake elicits mucosal enteric gliotic processes characterized by a hyperactivation of NLRP3/caspase-1/IL-1β signaling pathway, that contributes to further exacerbate the disruption of intestinal mucosal barrier integrity. However, we cannot rule out the contribution of NLRP3 inflammasome activation from other cells, such as immune cells, in IEB alterations associated with obesity. Overall, our results suggest that enteric glial NLRP3 inflammasome might represent an interesting molecular target for the development of novel pharmacological approaches aimed at managing the enteric inflammation and intestinal mucosal dysfunctions associated with obesity.

Accelerated BDNF expression in visceral white adipose tissues following high-fat diet feeding in mice.

Brain-derived neurotrophic factor (BDNF) is expressed in the white adipose tissues (WATs), and the expression increases during high-fat diet (HFD) feeding, implicating its role in obesity. Here, we focused on BDNF expression in epididymal WAT (eWAT), a visceral adipose tissue, in mice. During 2 weeks of HFD feeding, Bdnf mRNA expression in eWAT slightly increased, but a robust increase was observed after 8 weeks of HFD feeding. This upregulation of Bdnf mRNA was correlated with significant induction of hypoxia-inducible factor 1α (Hif1α) and platelet-derived growth factor subunit B (Pdgfb) mRNA in eWAT following 8 weeks of HFD feeding. Furthermore, the increased expression of the M1 macrophage markers was strongly correlated with the elevation of Bdnf mRNA in the eWAT. Notably, 8 weeks of HFD feeding significantly elevated Tnfα mRNA expression in eWAT, while no such induction was observed in inguinal WAT (iWAT). In contrast, the expression of Adipoq (adiponectin), implicated in improved insulin sensitivity and anti-inflammatory effects, was significantly upregulated in iWAT, but not in eWAT. Thus, our study may show the role of BDNF in eWAT in obesity models, potentially contributing to the pathological state of visceral adipose tissues.

Dysregulation of c-Jun (JUN) and FBJ murine osteosarcoma viral oncogene homolog B (FOSB) in obese people and their predictive values for metabolic syndrome.

The incidences of metabolic syndrome (MetS), denoting insulin resistance-associated various metabolic disorders, are increasing. This study aimed to identify new biomarkers for predicting MetS and provide a novel diagnostic approach. Herein, the expression profiles of c-Jun (JUN) and FBJ murine osteosarcoma viral oncogene homolog B (FOSB) in individuals with obesity and patients with MetS from the Gene Expression Omnibus database. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to evaluate the messenger RNA levels of JUN and FOSB in the peripheral blood of healthy volunteers (lean and obese) and patients with MetS (lean and obese), along with that in the adipose tissue and peripheral blood of obese mouse model. Furthermore, receiver operating characteristic (ROC) curve and logistic regression analyses were performed to determine the diagnostic value of JUN and FOSB in MetS. The expression profiles and RT-qPCR results showed that JUN and FOSB were highly expressed in individuals with obesity, obese mouse models, and patients with MetS. The ROC analysis results showed an area under the curve values of 0.872 and 0.879 for JUN, 0.802 and 0.962 for FOSB, and 0.946 and 0.979 for JUN-FOSB in the lean group and the group with obesity, respectively, in predicting MetS. Logistic regression analysis showed that the p-values of both JUN and FOSB as MetS-affecting factors were <0.05. Altogether, the findings of this study indicate that both JUN and FOSB, abnormally expressed in individuals with obesity, are good biomarkers of MetS.

Reversing Pdgfrβ signaling restores metabolically active beige adipocytes by alleviating ILC2 suppression in aged and obese mice

ObjectivePlatelet Derived Growth Factor Receptor Beta (Pdgfrβ) suppresses the formation of cold temperature-induced beige adipocytes in aged mammals. We aimed to determine if deleting Pdgfrβ in aged mice could rejuvenate metabolically active beige adipocytes by activating group 2 innate lymphoid cells (ILC2), and whether this effect could counteract diet-induced obesity-associated beige fat decline. MethodsWe employed Pdgfrβ gain-of-function and loss-of-function mouse models targeting beige adipocyte progenitor cells (APCs). Our approach included cold exposure, metabolic cage analysis, and age and diet-induced obesity models to examine beige fat development and metabolic function under varied Pdgfrβ activity. ResultsAcute cold exposure alone enhanced metabolic benefits in aged mice, irrespective of beige fat generation. However, Pdgfrβ deletion in aged mice reestablished the formation of metabolically functional beige adipocytes, enhancing metabolism. Conversely, constitutive Pdgfrβ activation in young mice stymied beige fat development. Mechanistically, Pdgfrβ deletion upregulated IL-33, promoting ILC2 recruitment and activation, whereas Pdgfrβ activation reduced IL-33 levels and suppressed ILC2 activity. Notably, diet-induced obesity markedly increased Pdgfrβ expression and Stat1 signaling, which inhibited IL-33 induction and ILC2 activation. Genetic deletion of Pdgfrβ restored beige fat formation in obese mice, improving whole-body metabolism. ConclusionsThis study reveals that cold temperature exposure alone can trigger metabolic activation in aged mammals. However, reversing Pdgfrβ signaling in aged and obese mice not only restores beige fat formation but also renews metabolic function and enhances the immunological environment of white adipose tissue (WAT). These findings highlight Pdgfrβ as a crucial target for therapeutic strategies aimed at combating age- and obesity-related metabolic decline.

Anemarrhena asphodeloides Bunge total saponins lower lipid via modulating MAOA activity to enhance defense mechanisms in mice and C. elegans

Ethnopharmacological relevanceWithin Anemarrhena asphodeloides Bunge (AAB), the pivotal bioactive constituents are identified as Anemarrhena asphodeloides Bunge total saponins (ABS). In traditional pharmacology, ABS has exhibited notable anti-inflammatory, hypoglycemic, and cardioprotective properties. Despite these observed effects, the specific protective mechanisms of ABS against metabolic diseases and improving the endocrine system remain largely uncharted. Aim to studyThis work intends to shed light on the effects and intrinsic mechanisms of ABS on metabolic diseases. Materials and methodsThe characterization of ABS components was achieved through High-Performance Liquid Chromatography/Mass Spectrometry (HPLC/MS). To evaluate ABS's anti-inflammatory efficacy, mouse macrophages underwent analysis using the Griess method. Induced differentiation of mouse fibroblasts was assessed through Oil Red O staining. In an obesity model with C57BL/6 N mice, ABS administration prompted measurements of glucose and insulin tolerance. Western blot analysis quantified lipolysis and anti-inflammatory protein expression. Nile red staining gauged body fat content in C. elegans post-ABS treatment. The mechanism of ABS action was elucidated through mRNA sequencing, further validated using RNA interference technology, and nematode mutants. ResultsABS showcased the ability to diminish Nitric Oxide (NO) production in inflammatory macrophages and shrink adipocyte lipid droplets. In mice experiments, ABS was effective in alleviating fat accumulation and affecting serum lipid metabolism in diabetic mice. It enhanced oral glucose tolerance and insulin tolerance while increasing lipolysis-associated protein expression. ABS notably reduced fat content in C. elegans. Mechanistically, ABS downregulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and monoamine oxidase A (MAOA) expression while enhancing UGT, ilys-2, and ilys-3. Lipolysis emerged as a pivotal pathway for ABS in the therapeutic intervention of metabolic diseases. ConclusionsOur investigation has revealed that ABS exert a role in combating metabolic diseases by enhancing the body's defense mechanisms. ABS activate the NLRP3-neurotransmitter-visceral adipose pathway in mice, thereby bolstering resistance and diminishing fat accumulation. In C. elegans, ABS downregulated the expression of MAOA, bolstered resistance, and augmented glucuronidase activity, consequently leading to a reduction in fat content.

The vices and virtues of medical models of obesity.

Despite numerous public health organizations supporting the pathologization of obesity and considering recent obesity rates a health crisis, many researchers in the humanities, social sciences, and even in the health sciences remain unconvinced. In this paper, we address a set of arguments coming from these academic fields that criticize medical models of obesity for their supposedly flawed diagnostic categories that shift focus onto individuals and support moralizing judgements. Clarifying some key claims in these models and explicating the view of obesity in terms of energy dysregulation, we aim to tease apart misunderstandings and argue that not only do these models not say what they are often accused of saying, but their apparent vices may actually be virtues in helping to combat stigma. Building on the social psychology of stigma and disease labeling, we then suggest that current medical models are largely supportive of many moral and political aims promoted by critics of these models.

3,5-Dimethyl-2,4,6-trimethoxychalcone Lessens Obesity and MAFLD in Leptin-Deficient ob/ob Mice.

Chalcones constitute an important group of natural compounds abundant in fruits and comestible plants. They are a subject of increasing interest because of their biological activities, including anti-diabetic and anti-obesity effects. The simple chalcone structural scaffold can be modified at multiple sites with different chemical moieties. Here, we generated an artificial chalcone, i.e., 3,5-dimethyl-2,4,6-trimethoxychalcone (TriMetChalc), derived from 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC). DMC is a major compound of Cleistocalyx operculatus, a plant widely used in Asia for its anti-hyperglycemic activity. Using ob/ob mice as an obesity model, we report that, after 3 weeks of per os administration, TriMetChalc modified food intake through the specific activation of brain structures dedicated to the regulation of energy balance. TriMetChalc also decreased weight gain, glucose intolerance, and hepatic steatosis. Moreover, through extensive liver lipidomic analysis, we identified TriMetChalc-induced modifications that could contribute to improving the liver status of the animals. Hence, TriMetChalc is a chalcone derivative capable of reducing food intake and the addition of glucose intolerance and hepatic steatosis in a mouse model of obesity. In light of these results, we believe that TriMetChalc action deserves to be more deeply evaluated over longer treatment periods and/or in combination with other chalcones with protective effects on the liver.

Anti-obesity and immunomodulatory effects of Allium hookeri leaves cultivated with artificial light of different intensities on immune-depressed obese mice

This study was conducted to evaluate the effects of Allium hookeri (AH) leaves cultivated with different light-emitting diode (LED) intensities (L: low, 100 μmol/m2/s; M: medium, 150 μmol/m2/s; H: high, 200 μmol/m2/s). Alliin concentration increased as light intensity increased in AH and showed the highest level at LED-H condition. The anti-obesity and immunomodulatory properties of AH were evaluated in a cyclophosphamide (CPA)-induced immunosuppressed obese animal model. C57BL/6 J mice were randomly divided into control (CON), high-fat diet (HFD) control (CON-H), negative control (NC), positive control (PC, β-glucan, 50 mg/kg body weight (BW)), AH L, M, and H groups. The three kinds of AH extracts were orally administered to the mice at 300 mg/kg BW for 2 weeks. Except for CON and CON-H, all the other groups were intraperitoneally treated with CPA. Epididymal and abdominal fat weight decreased as LED intensity increased while spleen weight increased in the AH groups. Serum glucose decreased as LED intensity increased in the AH groups and H group showed the lowest level. Triglycerides, total, and LDL-cholesterol levels decreased while HDL-cholesterol level increased in the AH groups compared to the NC group. Moreover, AH effectively reduced serum ALT and AST levels and increased the total white blood cell count, particularly elevating lymphocyte and monocyte levels. Furthermore, NK cell activity was higher in the AH groups. These findings suggest that AH cultivated at optimal LED intensity could be used as a novel biomedicine and in pharmacotherapy to treat related diseases to improve public health without any toxicity.

Maid gene dysfunction promotes hyperobesity via the reduction of adipose tissue inflammation in Mc4r gene-deficient mice

The onset and progression mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are being studied. We developed and analyzed a new mouse model of obesity by combining maternal Id-like molecule (Maid) and melanocortin-4 receptor (Mc4r) gene deletions. Four mice, each at 12 and 28 weeks of age, were analyzed for each genotype: Maid gene knockout, Mc4r gene knockout, combined Mc4r and Maid gene knockout, and Mc4r gene knockout with a high-fat diet. Mice with a combined deficiency of Mc4r and Maid gene showed significantly more severe obesity compared to all other genotypes, but no liver fibrosis or a decline in metabolic status were observed. In visceral white adipose tissue, Maid and Mc4r gene knockout mice had fewer CD11c-positive cells and lower mRNA expression of both inflammatory and anti-inflammatory cytokines. Furthermore, Maid and Mc4r gene knockout mice showed lower expression of adipocytokines in visceral white adipose tissue and uncoupling protein-1 in scapular brown adipose tissue. The expression of adipocytokines and uncoupling protein-1 is regulated by sympathetic nerve signaling that contribute severe obesity in Maid and Mc4r gene knockout mice. These mechanisms contribute hyperobesity in Maid and Mc4r gene knockout mice.

Magnitude of Obesity Alone does not Alter the Alveolar Lipidome.

Obesity may lead to pulmonary dysfunction through complex and incompletely understood cellular and biochemical effects. Altered lung lipid metabolism has been identified as a potential mechanism of lung dysfunction in obesity. While murine models of obesity demonstrate changes in pulmonary surfactant phospholipid composition and function, data in humans are lacking. We measured untargeted shotgun lipidomes in two bronchoalveolar lavages (BAL) from apical and anteromedial pulmonary subsegments of 14 adult subjects (7 males and 7 females) with body mass indexes ranging from 24.3 to 50.9 kg/m2. The lipidome composition was characterized at the class, species, and fatty acyl / alkyl level using total lipid molecular ion signal intensities normalized to BAL protein concentration and epithelial lining fluid volumes. Multivariate analyses were conducted to identify potential changes with increasing BMI. The alveolar lipidomes contained the expected composition of surfactant associated phospholipids, sphingolipids, and sterols in addition to cardiolipin and intracellular signaling lipid species. No significant differences in lipidomes were detected between the two BAL regions. Though a small number of lipid species were associated with BMI in multivariate analyses, no robust differences in lipidome composition or specific lipid species were identified over the range of body habitus. The magnitude of obesity alone does not substantially alter the alveolar lipidome in patients without lung disease. Differences in lung function in patients with obesity and no lung disease are unlikely related to changes in alveolar lipid composition.

The effects of brown rice as functional food on Lee Index, adipose tissues and PRDM16 levels in obesity model &lt;i&gt;Rattus norvegicus&lt;/i&gt;

Brown rice is a functional food known to improve the Lee Index, influencing PRDM16 levels in obesity conditions. Therefore, this study aims to determine the differences in Lee Index, Brown Adipose Tissue (BAT) weight, White Adipose Tissue (WAT) weight, BeAT weight, total body fat, and PRDM16 levels of obese model rats with the intervention of brown and white rice, as well as ℽ-oryzanol. A true experimental method was used with a post-test-only control group in vivo design. The obesity model was constructed with male Sprague Dawley rats (Rattus norvegicus), divided into five diet groups namely standard and HFHF diet control, as well as HFHF + brown rice, HFHF + white rice, and HFHF + ℽ-oryzanol combination diet. The experiment was carried out for 26 weeks, with details of 14 weeks to form an obese model and 12 weeks for the intervention. Before statistical correlation was tested, Lee index values, adipose tissues, and PRDM16 were analyzed. The anthropometric data collection method was carried out by weighing before and after the intervention, while adipose tissue was collected by weighing after sacrifice. The immunofluorescence method was used to collect the expression of PRDM16 and the mean of PRDM16 levels was analyzed in the ImageJ application. After the data collection process, analysis was performed using SPSS to determine possible differences in each group. Normally distributed data were analyzed using One-Way ANOVA, while those without normal distribution were assessed using the Kruskall-Walis method and the Mann Whitney-U advanced test, with a p-value of &lt;0.05 considered significantly different.The result showed that there were differences among several groups regarding total body fat (p=0.012), WAT (p=0.026), and BAT (p=0.025). However, no differences were found between all groups regarding the Lee index (p=0.275), BeAT (p=0.079), and PRDM16 level (p=0.292). In conclusion, brown rice intervention did not significantly affect Lee index values, the expression of PRDM16, and adipose tissue weights at the end of the intervention.

A novel Osteoarthritis scoring system to separate typical OA joint degeneration from non-typical lesions in male Sprague Dawley rats

ObjectiveTo develop a novel scoring system to characterize osteoarthritis-related degeneration distinct from spontaneous subchondral bone lesions observed in the tibia and femur of male Sprague Dawley rats. MethodKnee joints from male rats following 12 weeks of a diet-induced obesity model of osteoarthritis (OA) were assessed. OA histopathological changes (OAHC) were assessed in the knee joints. All scores were evaluated using a modified Mankin score and a modified Osteoarthritis Research Society International histological score. OAHC were divided into 3 categories: (I) Typical OA score evaluating the changes in cartilage structure, cellularity, proteoglycan depletion, and tidemark integrity, (II) A novel Non-typical OA score evaluating cartilage integrity, and the size of local thickening, fragmentation and degeneration along the tidemark and the size and severity of the subchondral bone lesion, and (III) Total OA score comprised of both, the Typical and the Non-typical scores. ResultsRats exposed to a high fat/high sucrose diet had higher Typical OA score compared to a control group (Chow). Non-typical and Total OA scores revealed no differences in the severity of the lesions between the HFS and the Chow group animals. All scoring systems had excellent intra- and inter-examiner reliability. ConclusionThe spontaneous bone lesions observed in male Sprague Dawley rats can obscure the effect of the diet-induced obesity if the classical scoring system is used to assess joint degeneration. The newly proposed scoring method provides a reliable method to distinguish classical OA joint degeneration from spontaneous Non-typical lesions occurring in these rats.

Integrated Ultrasound Characterization of the Diet-Induced Obesity (DIO) Model in Young Adult c57bl/6j Mice: Assessment of Cardiovascular, Renal and Hepatic Changes.

Consuming an unbalanced diet and being overweight represent a global health problem in young people and adults of both sexes, and may lead to metabolic syndrome. The diet-induced obesity (DIO) model in the C57BL/6J mouse substrain that mimics the gradual weight gain in humans consuming a "Western-type" (WD) diet is of great interest. This study aims to characterize this animal model, using high-frequency ultrasound imaging (HFUS) as a complementary tool to longitudinally monitor changes in the liver, heart and kidney. Long-term WD feeding increased mice body weight (BW), liver/BW ratio and body condition score (BCS), transaminases, glucose and insulin, and caused dyslipidemia and insulin resistance. Echocardiography revealed subtle cardiac remodeling in WD-fed mice, highlighting a significant age-diet interaction for some left ventricular morphofunctional parameters. Qualitative and parametric HFUS analyses of the liver in WD-fed mice showed a progressive increase in echogenicity and echotexture heterogeneity, and equal or higher brightness of the renal cortex. Furthermore, renal circulation was impaired in WD-fed female mice. The ultrasound and histopathological findings were concordant. Overall, HFUS can improve the translational value of preclinical DIO models through an integrated approach with conventional methods, enabling a comprehensive identification of early stages of diseases in vivo and non-invasively, according to the 3Rs.

Корекція пробіотиком пародонтального синдрому у тварин за умов ожиріння і хронічного стресу

The aim of this study was to investigate the effect of obesity and chronic stress on periodontal tissues, both separately and in the combined comorbidity of these conditions in rats, and the role of the probiotic Lactobacillus casei in the correction of periodontal syndrome under these conditions. Methods. The development of periodontal syndrome and the effectiveness of the probiotic Lactobacillus casei IMV B-7280, administered to rats from one month of age intragastrically in a volume of 1 mL (5 · 108 CFU) in two-week courses with breaks of 2 weeks, were studied in a model of glutamate-induced obesity and chronic stress - in combination and separately. In periodontal tissues, the total proteolytic and antitryptic activity, free fucose and glycosaminoglycans (GAG) content, catalase activity, thiobarbiturate active products (TBA reagents), and the content of oxidatively modified proteins (OMP) and molecules of average mass (AMM) were determined; in bone tissue, the molar root exposure coefficient was calculated. The anthropometric parameters of the animals and the Selye triad were studied. Results. We have substantiated the development of periodontal syndrome in animals with glutamate-induced obesity against the background of chronic stress, as evidenced by the activation of free radical oxidation of lipids and proteins, depolymerization of fucoproteins and proteoglycans of periodontal connective tissue, which causes exposure of molar roots by almost 65%. The administration of the probiotic Lactobacillus casei in two-week courses with intervals of 2 weeks to obese rats with chronic stress prevented the development of obesity, as evidenced by a significant decrease in visceral fat mass, Li index, and BMI, as well as the severity of stress syndrome, as evidenced by a decrease in ulcer formation, thymus involution, and adrenal hypertrophy. The periodontoprotective effect of Lactobacillus casei under the combined influence of obesity and chronic stress was proved by significant changes in oxidative stress, free fucose, and GAG content and a 1.5-times decrease in the molar root exposure ratio. Conclusions. Periodic administration of Lactobacillus casei to rats treated with sodium glutamate in the neonatal period against the background of chronic stress prevented the development of obesity, the severity of stress syndromeб and damage to periodontal tissues, as evidenced by the prevention of oxidative stress, increased catabolism of extracellular connective tissue proteins and antiresorptive effect.

Cardiac Troponin to Adjudicate Subclinical Heart Failure in Diabetic Patients and a Murine Model of Metabolic Syndrome.

Cardiovascular disease, kidney health, and metabolic disease (CKM) syndrome is associated with significant morbidity and mortality, particularly from congestive heart failure (CHF). Guidelines recommend measurement of cardiac troponin (cTn) to identify subclinical heart failure (HF) in diabetics/CKM. However, appropriate thresholds and the impact from routine screening have not been elucidated. cTnI was assessed using the Abbott high sensitivity (hs)-cTnI assay in outpatients with physician-ordered hemoglobin A1c (Hb A1c) and associated with cardiac comorbidities/diagnoses, demographics, and estimated glomerular filtration rate (eGFR). Risk thresholds used in CKM staging guidelines of >10 and >12 ng/L for females and males, respectively, were used. Multivariate logistic regression was applied. hs-cTnI was assessed in a high-fat-diet induced murine model of obesity and diabetes. Of 1304 patients, 8.0% females and 15.7% males had cTnI concentrations above the risk thresholds. Thirty-one (4.2%) females and 23 (4.1%) males had cTnI above the sex-specific 99% upper reference limit. A correlation between hs-cTnI and Hb A1c (R = 0.2) and eGFR (R = -0.5) was observed. hs-cTnI concentrations increased stepwise based on A1C of <5.7% (median = 1.5, IQR:1.3-1.8), 5.7%-6.4% (2.1, 2.0-2.4), 6.5%-8.0% (2.8, 2.5-3.2), and >8% (2.8, 2.2-4.3). Male sex (P < 0.001), eGFR (P < 0.001), and CHF (P = 0.004) predicted elevated hs-cTnI. Obese and diabetic mice had increased hs-cTnI (7.3 ng/L, 4.2-10.4) relative to chow-fed mice (2.6 ng/L, 1.3-3.8). A high proportion of outpatients with diabetes meet criteria for subclinical HF using hs-cTnI measurements. Glucose control is independently associated with elevated cTnI, a finding replicated in a murine model of metabolic syndrome.

Reliable prediction of childhood obesity using only routinely collected EHRs may be possible

BackgroundEarly identification of children at high risk of obesity can provide clinicians with the information needed to provide targeted lifestyle counseling to high-risk children at a critical time to change the disease course. ObjectivesThis study aimed to develop predictive models of childhood obesity, applying advanced machine learning methods to a large unaugmented electronic health record (EHR) dataset. This work improves on other studies that have (i) relied on data not routinely available in EHRs (like prenatal data), (ii) focused on single-age predictions, or (iii) not been rigorously validated. MethodsA customized sequential deep-learning model to predict the development of obesity was built, using EHR data from 36,191 diverse children aged 0–10 years. The model was evaluated using extensive discrimination, calibration, and utility analysis; and was validated temporally, geographically, and across various subgroups. ResultsOur results are mostly better or comparable to similar studies. Specifically, the model achieved an AUROC above 0.8 in all cases (with most cases around 0.9) for predicting obesity within the next 3 years for children 2–7 years of age. Validation results show the model's robustness and top predictors match important risk factors of obesity. ConclusionsOur model can predict the risk of obesity for young children at multiple time points using only routinely collected EHR data, greatly facilitating its integration into clinical care. Our model can be used as an objective screening tool to provide clinicians with insights into a patient's risk for developing obesity so that early lifestyle counseling can be provided to prevent future obesity in young children.

The Effects of 1-Kestose on the Abundance of Inflammation-Related Gene mRNA in Adipose Tissue and the Gut Microbiota Composition in Rats Fed a High-Fat Diet.

Chronic inflammation in adipose tissue is thought to contribute to insulin resistance, which involves the gut microbiota. Our previous studies have demonstrated that ingestion of 1-kestose can alter the gut microbiota composition, increase cecal butyrate levels, and improve insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Additionally, we found that 1-kestose supplementation ameliorated insulin resistance in obese rat models fed a high-fat diet (HFD), although the effects of 1-kestose on the abundance of inflammation-related gene in adipose tissue and gut microbiota composition in these rats were not explored. This study aimed to investigate the impact of 1-kestose on these parameters in HFD-fed rats, compared to OLETF rats. Male Sprague-Dawley rats were divided into two dietary groups, control or HFD, for 19 wk. Each group was further subdivided to receive either tap water or tap water supplemented with 2% (w/v) 1-kestose throughout the study. We evaluated gene expression in adipose tissue, as well as short-chain fatty acids (SCFAs) levels and microbial composition in the cecum contents. 1-Kestose intake restored the increased relative abundance of tumor necrosis factor (Tnf) mRNA in adipose tissue and the reduced level of butyrate in the cecum contents of HFD-fed rats to those observed in control diet-fed rats. Additionally, 1-kestose consumption changed the composition of the gut microbiota, increasing Butyricicoccus spp., decreasing UGC-005 and Streptococcus spp., in the cecum contents of HFD-fed rats. Our findings suggest that 1-kestose supplementation reduces adipose tissue inflammation and increases butyrate levels in the gut of HFD-fed rats, associated with changes in the gut microbiota composition, distinct from those seen in OLETF rats.

Influence of Lipid Class Used for Omega-3 Fatty Acid Supplementation on Liver Fat Accumulation in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) occurs in subjects with obesity and metabolic syndrome. MASLD may progress from simple steatosis (i.e., hepatic steatosis) to steatohepatitis, characterized by inflammatory changes and liver cell damage, substantially increasing mortality. Lifestyle measures associated with weight loss and/or appropriate diet help reduce liver fat accumulation, thereby potentially limiting progression to steatohepatitis. As for diet, both total energy and macronutrient composition significantly influence the liver's fat content. For example, the type of dietary fatty acids can affect the metabolism of lipids and hence their tissue accumulation, with saturated fatty acids having a greater ability to promote fat storage in the liver than polyunsaturated ones. In particular, polyunsaturated fatty acids of n-3 series (omega-3), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been intensively studied for their antisteatotic effects, both in preclinical animal models of obesity and hepatic steatosis and in overweight/obese patients. Their effects may depend not only on the dose and duration of administration of omega-3, or DHA/EPA ratio, but also on the lipid class used for their supplementation. This review summarizes the available evidence from recent comparative studies using omega-3 supplementation via different lipid classes. Albeit the evidence is mainly limited to preclinical studies, it suggests that phospholipids and possibly wax esters could provide greater efficacy against MASLD compared to traditional chemical forms of omega-3 supplementation (i.e., triacylglycerols, ethyl esters). This cannot be attributed solely to improved EPA and/or DHA bioavailability, but other mechanisms may be involved. Keywords: MASLD • Metabolic dysfunction-associated steatotic liver disease • NAFLD • Non-alcoholic fatty liver disease • n-3 polyunsaturated fatty acids.