Cortical hypertrophy in intramuscular hemangioma mimicking bone tumor.

Although hemangiomas are the most common soft tissue tumors, intramuscular hemangiomas account for only 0.8% of all vascular tumors. These lesions are rarely located adjacent to the bone and cause changes in the adjacent bone. They are often mistakenly diagnosed as bone tumors. In this study, a case of a 19-year-old male patient with intramuscular hemangioma causing cortical thickening was reported.

Otitis media with effusion in preschool children with adenoid hypertrophy: Risk factors and nursing care.

AIM: To evaluate the influencing factors of otitis media with effusion (OME) in children with adenoid hypertrophy and to provide evidence for clinical treatment and care of children with adenoid hypertrophy. DESIGN: A retrospective study. METHODS: Preschool children with adenoid hypertrophy treated in our hospital from 1 January 2021 to 30 July 2022 were included. We analysed the characteristics of OME and non-OME children with adenoid hypertrophy. Pearson correlation analysis and logistic regression analysis were performed to evaluate the risk factors for OME in children with adenoid hypertrophy. CONCLUSION: A total of 166 children with adenoid hypertrophy were included; the incidence of OME in children with adenoid hypertrophy was 34.94%. The incidence of OME decreased significantly with the increase in age (p = 0.014). Logistic regression analysis showed that age < 3 years (OR = 3.149, 95%CI: 2.812-3.807) and duration of adenoid hypertrophy ≥12 months (OR = 2.326, 95%CI: 2.066-2.612) were the risk factors of OME in children with adenoid hypertrophy (all p < 0.05). PATIENT CONTRIBUTION: The incidence of adenoid hypertrophy with OME is high in preschool children, and it is related to the age and duration of adenoid hypertrophy.

No drains in reduction mammaplasty - a systematic review.

Breast reduction mammaplasty is the only effective therapeutic intervention for patients with symptomatic breast hypertrophy. In this procedure, closed suction drains have become a standard of care, while the literature supporting use of drains is lacking. In fact, with emerging data we found out that drains might not be so necessary. This review aimed to systematically compare the number of complications in drained and undrained breasts and to evaluate the safety of omitting drains in reduction mammaplasty in clinical practice. A systematic review of literature was conducted identifying all studies on drainage in reduction mammaplasty. The analysed databases revealed 13 eligible studies to be included in this review. There were 308 drained breasts and 859 undrained breasts in total in patients from 16 to 73 years of age. The resected tissue weight per side fluctuated from 108 to 1,296 grams. In total, there was only 2.4% incidence of haematoma complications in undrained breasts and 3.9% in drained breasts. Closed suction drains are still being routinely used in reduction mammaplasty, although aborting drain use is proven to be not only safe, but advantageous. The clear benefit is increased patient comfort, shortened hospital stay, decreased cost of the procedure and nurse care, and decreased rate of complications.

Effects of adenoid hypertrophy on nasopharyngeal airway ventilation: A computational fluid dynamics study.

OBJECTIVES: Adenoid hypertrophy causes impaired nasopharyngeal airways (NA) ventilation. However, it is difficult to evaluate the ventilatory conditions of NA. Therefore, this study aimed to analyze the nasopharyngeal airway resistance (NARES) based on computational fluid dynamics simulations and the nasopharyngeal airway depth (NAD) and adenoid hypertrophy grade measured on cephalometric cone-beam computed tomography images and determine the relationship between NAD and grade and NARES to ultimately assess using cephalometric measurements whether NA has airway obstruction defects. METHODS: Cephalogram images were generated from cone-beam computed tomography data of 102 children (41 boys; mean age: 9.14 ± 1.43 years) who received orthodontic examinations at an orthodontic clinic from September 2012 to March 2023, and NAD and adenoid grade and NARES values were measured based on computational fluid dynamics analyses using a 3D NA model. Nonlinear regression analyses were used to evaluate the relationship between NARES and NAD and correlation coefficients to evaluate the relationship between grade and NARES. RESULTS: NARES was inversely proportional to the cube of NAD (R2 = 0.786, P < 0.001), indicating a significant relationship between these variables. The resistance NARES increased substantially when the distance NAD was less than 5 mm. However, adenoid Grade 4 (75 % hypertrophy) was widely distributed. CONCLUSIONS: These study findings demonstrate that the ventilatory conditions of NA can be determined based on a simple evaluation of cephalogram images. An NAD of less than 5 mm on cephalometric images results in NA obstruction with substantially increased airflow resistance.

Circular RNAs: Biogenesis, Functions, and Role in Myocardial Hypertrophy.

Circular RNAs (circRNAs) are a large class of endogenous single-stranded covalently closed RNA molecules. High-throughput RNA sequencing and bioinformatic algorithms have identified thousands of eukaryotic circRNAs characterized by high stability and tissue-specific expression pattern. Recent studies have shown that circRNAs play an important role in the regulation of physiological processes in the norm and in various diseases, including cardiovascular disorders. The review presents current concepts of circRNA biogenesis, structural features, and biological functions, describes the methods of circRNA analysis, and summarizes the results of studies on the role of circRNAs in the pathogenesis of hypertrophic cardiomyopathy, the most common inherited heart disease.

[Effect and mechanism of Linggui Zhugan Decoction in regulating Sig1R on Angâ ¡-induced cardiomyocyte hypertrophy].

This study aims to explore the mechanism of Linggui Zhugan Decoction(LGZGD) in inhibiting Angiotensin Ⅱ(AngⅡ)-induced cardiomyocyte hypertrophy by regulating sigma-1 receptor(Sig1R). The model of H9c2 cardiomyocyte hypertrophy induced by AngⅡ in vitro was established by preparing LGZGD-containing serum and blank serum. H9c2 cells were divided into normal group, AngⅡ model group, 20% normal rat serum group(20% NSC), and 20% LGZGD-containing serum group. After the cells were incubated with AngⅡ(1 µmol·L~(-1)) or AngⅡ with serum for 72 h, the surface area of cardiomyocytes was detected by phalloidine staining, and the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase were detected by micromethod. The mitochondrial Ca~(2+) levels were detected by flow cytometry, and the expression levels of atrial natriuretic peptide(ANP), brain natriuretic peptide(BNP), Sig1R, and inositol 1,4,5-triphosphate receptor type 2(IP_3R_2) were detected by Western blot. The expression of Sig1R was down-regulated by transfecting specific siRNA for investigating the efficacy of LGZGD-containing serum on cardiomyocyte surface area, Na~+-K~+-ATPase activity, Ca~(2+)-Mg~(2+)-ATPase activity, mitochondrial Ca~(2+), as well as ANP, BNP, and IP_3R_2 protein expressions. The results showed that compared with the normal group, AngⅡ could significantly increase the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.01), and it could decrease the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+), and the expression of Sig1R(P<0.01). In addition, IP_3R_2 protein expression was significantly increased(P<0.01). LGZGD-containing serum could significantly decrease the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.05, P<0.01), and it could increase the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+ )(P<0.01), and the expression of Sig1R(P<0.05). In addition, IP_3R_2 protein expression was significantly decreased(P<0.05). However, after Sig1R was down-regulated, the effects of LGZGD-containing serum were reversed(P<0.01). These results indicated that the LGZGD-containing serum could inhibit cardiomyocyte hypertrophy induced by AngⅡ, and its pharmacological effect was related to regulating Sig1R, promoting mitochondrial Ca~(2+ )inflow, restoring ATP synthesis, and protecting mitochondrial function.

Cytotoxic Cyclolignans Obtained by the Enlargement of the Cyclolignan Skeleton of Podophyllic Aldehyde, a Selective Podophyllotoxin-Derived Cyclolignan.

Podophyllotoxin, a cyclolignan natural product, has been the object of extensive chemomodulation to obtain better chemotherapeutic agents. Among the obtained podophyllotoxin derivatives, podophyllic aldehyde showed very interesting potency and selectivity against several tumoral cell lines, so it became our lead compound for further modifications, as described in this work, oriented toward the enlargement of the cyclolignan skeleton. Thus, modifications performed at the aldehyde function included nucleophilic addition reactions and the incorporation of the aldehyde carbon into several five-membered rings, such as thiazolidinones and benzo-fused azoles. The synthesized derivatives were evaluated against several types of cancer cells, and although some compounds were cytotoxic at the nanomolar range, most of them were less potent and less selective than the parent compound podophyllic aldehyde, with the most potent being those having the lactone ring of podophyllotoxin. In silico ADME evaluation predicted good druggability for most of them. The results indicate that the γ-lactone ring is important for potency, while the α,ß-unsaturated aldehyde is necessary to induce selectivity in these cyclolignans.

D-Allulose Reduces Hypertrophy and Endoplasmic Reticulum Stress Induced by Palmitic Acid in Murine 3T3-L1 Adipocytes.

Natural rare sugars are an alternative category of sweeteners with positive physiologic and metabolic effects both in in vitro and animal models. D-allulose is a D-fructose epimer that combines 70% sucrose sweetness with the advantage of an extremely low energy content. However, there are no data about the effect of D-allulose against adipose dysfunction; thus, it remains to be confirmed whether D-allulose is useful in the prevention and in treatment of adipose tissue alterations. With this aim, we evaluated D-allulose's preventive effects on lipid accumulation in 3T3-L1 murine adipocytes exposed to palmitic acid (PA), a trigger for hypertrophic adipocytes. D-allulose in place of glucose prevented adipocyte hypertrophy and the activation of adipogenic markers C/EBP-ß and PPARγ induced by high PA concentrations. Additionally, D-allulose pretreatment inhibited the NF-κB pathway and endoplasmic reticulum stress caused by PA, through activation of the Nrf2 pathway. Interestingly, these effects were also observed as D-allulose post PA treatment. Although our data need to be confirmed through in vivo models, our findings suggest that incorporating D-allulose as a glucose substitute in the diet might have a protective role in adipocyte function and support a unique mechanism of action in this sugar as a preventive or therapeutic compound against PA lipotoxicity through the modulation of pathways connected to lipid transport and metabolism.

Dopamine D2 receptor antagonist counteracts hyperglycemia and insulin resistance in diet-induced obese male mice.

Obesity leads to insulin resistance (IR) and type 2 diabetes. In humans, low levels of the hormone prolactin (PRL) correlate with IR, adipose tissue (AT) dysfunction, and increased prevalence of T2D. In obese rats, PRL treatment promotes insulin sensitivity and reduces visceral AT adipocyte hypertrophy. Here, we tested whether elevating PRL levels with the prokinetic and antipsychotic drug sulpiride, an antagonist of dopamine D2 receptors, improves metabolism in high fat diet (HFD)-induced obese male mice. Sulpiride treatment (30 days) reduced hyperglycemia, IR, and the serum and pancreatic levels of triglycerides in obese mice, reduced visceral and subcutaneous AT adipocyte hypertrophy, normalized markers of visceral AT function (PRL receptor, Glut4, insulin receptor and Hif-1α), and increased glycogen stores in skeletal muscle. However, the effects of sulpiride reducing hyperglycemia were also observed in obese prolactin receptor null mice. We conclude that sulpiride reduces obesity-induced hyperglycemia by mechanisms that are independent of prolactin/prolactin receptor activity. These findings support the therapeutic potential of sulpiride against metabolic dysfunction in obesity.

The redox-active defensive Selenoprotein T as a novel stress sensor protein playing a key role in the pathophysiology of heart failure.

Maladaptive cardiac hypertrophy contributes to the development of heart failure (HF). The oxidoreductase Selenoprotein T (SELENOT) emerged as a key regulator during rat cardiogenesis and acute cardiac protection. However, its action in chronic settings of cardiac dysfunction is not understood. Here, we investigated the role of SELENOT in the pathophysiology of HF: (i) by designing a small peptide (PSELT), recapitulating SELENOT activity via the redox site, and assessed its beneficial action in a preclinical model of HF [aged spontaneously hypertensive heart failure (SHHF) rats] and against isoproterenol (ISO)-induced hypertrophy in rat ventricular H9c2 and adult human AC16 cardiomyocytes; (ii) by evaluating the SELENOT intra-cardiomyocyte production and secretion under hypertrophied stimulation. Results showed that PSELT attenuated systemic inflammation, lipopolysaccharide (LPS)-induced macrophage M1 polarization, myocardial injury, and the severe ultrastructural alterations, while counteracting key mediators of cardiac fibrosis, aging, and DNA damage and restoring desmin downregulation and SELENOT upregulation in the failing hearts. In the hemodynamic assessment, PSELT improved the contractile impairment at baseline and following ischemia/reperfusion injury, and reduced infarct size in normal and failing hearts. At cellular level, PSELT counteracted ISO-mediated hypertrophy and ultrastructural alterations through its redox motif, while mitigating ISO-triggered SELENOT intracellular production and secretion, a phenomenon that presumably reflects the extent of cell damage. Altogether, these results indicate that SELENOT could represent a novel sensor of hypertrophied cardiomyocytes and a potential PSELT-based new therapeutic approach in myocardial hypertrophy and HF.

Optogenetic control of mRNA condensation reveals an intimate link between condensate material properties and functions.

Biomolecular condensates, often assembled through phase transition mechanisms, play key roles in organizing diverse cellular activities. The material properties of condensates, ranging from liquid droplets to solid-like glasses or gels, are key features impacting the way resident components associate with one another. However, it remains unclear whether and how different material properties would influence specific cellular functions of condensates. Here, we combine optogenetic control of phase separation with single-molecule mRNA imaging to study relations between phase behaviors and functional performance of condensates. Using light-activated condensation, we show that sequestering target mRNAs into condensates causes translation inhibition. Orthogonal mRNA imaging reveals highly transient nature of interactions between individual mRNAs and condensates. Tuning condensate composition and material property towards more solid-like states leads to stronger translational repression, concomitant with a decrease in molecular mobility. We further demonstrate that ß-actin mRNA sequestration in neurons suppresses spine enlargement during chemically induced long-term potentiation. Our work highlights how the material properties of condensates can modulate functions, a mechanism that may play a role in fine-tuning the output of condensate-driven cellular activities.

Cardioprotective Potential of Cymbopogon citratus Essential Oil against Isoproterenol-induced Cardiomyocyte Hypertrophy: Possible Involvement of NLRP3 Inflammasome and Oxidative Phosphorylation Complex Subunits.

OBJECTIVE: Cymbopogon citratus (DC.) Stapf is a medicinal and edible herb that is widely used for the treatment of gastric, nervous and hypertensive disorders. In this study, we investigated the cardioprotective effects and mechanisms of the essential oil, the main active ingredient of Cymbopogon citratus, on isoproterenol (ISO)-induced cardiomyocyte hypertrophy. METHODS: The compositions of Cymbopogon citratus essential oil (CCEO) were determined by gas chromatography-mass spectrometry. Cardiomyocytes were pretreated with 16.9 µg/L CCEO for 1 h followed by 10 µmol/L ISO for 24 h. Cardiac hypertrophy-related indicators and NLRP3 inflammasome expression were evaluated. Subsequently, transcriptome sequencing (RNA-seq) and target verification were used to further explore the underlying mechanism. RESULTS: Our results showed that the CCEO mainly included citronellal (45.66%), geraniol (23.32%), and citronellol (10.37%). CCEO inhibited ISO-induced increases in cell surface area and protein content, as well as the upregulation of fetal gene expression. Moreover, CCEO inhibited ISO-induced NLRP3 inflammasome expression, as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3, ASC, CASP1, GSDMD, and IL-1ß, as well as reduced protein levels of NLRP3, ASC, pro-caspase-1, caspase-1 (p20), GSDMD-FL, GSDMD-N, and pro-IL-1ß. The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated cardiomyocytes. Our further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1, Sdhd, mt-Cytb, Uqcrq, and mt-Atp6 but had no obvious effects on mt-Col expression. CONCLUSION: CCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.

Extranodal Rosai-Dorfman disease manifesting as Sjögren's syndrome combined with panuveitis and hypertrophic pachymeningitis: a case report and review of literature.

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by massive lymphadenopathy and systemic extranodal lesions. We present the case of a 28-year-old woman who presented with recurrent blurred vision in her right eye for 3 months. She developed blindness and atrophy in her left eye a decade prior to presentation. She subsequently developed headache, fever, and impaired mental status. Cranial magnetic resonance imaging indicated hypertrophic pachymeningitis (HP), and 18F-fluoro-2-deoxy-2-d-glucose (FDG) positron emission tomography/computed tomography revealed significant FDG uptake in the left dura mater. Autoimmune testing revealed elevated anti-nuclear, anti-SS-A, and anti-SS-B antibody levels. Incisional biopsy of the atrophic eyeball revealed RDD with marked polyclonal plasmacytosis. The patient was diagnosed with RDD accompanied by multisystem involvement, including Sjögren's syndrome (SS), panuveitis, and HP. Treatment with methylprednisolone for several weeks resulted in significant improvement. This is the first reported case of RDD presenting with SS in combination with panuveitis and HP. Although RDD is rarely diagnosed in young patients, interdisciplinary collaboration is essential to prevent a delayed diagnosis.

Mesenchymal stromal cell chondrogenesis under ALK1/2/3-specific BMP inhibition: a revision of the prohypertrophic signalling network concept.

BACKGROUND: In vitro chondrogenesis of mesenchymal stromal cells (MSCs) driven by the essential chondro-inducer transforming growth factor (TGF)-ß is instable and yields undesired hypertrophic cartilage predisposed to bone formation in vivo. TGF-ß can non-canonically activate bone morphogenetic protein-associated ALK1/2/3 receptors. These have been accused of driving hypertrophic MSC misdifferentiation, but data remained conflicting. We here tested the antihypertrophic capacity of two highly specific ALK1/2/3 inhibitors - compound A (CompA) and LDN-212854 (LDN21) - in order to reveal potential prohypertrophic contributions of these BMP/non-canonical TGF-ß receptors during MSC in vitro chondrogenesis. METHODS: Standard chondrogenic pellet cultures of human bone marrow-derived MSCs were treated with TGF-ß and CompA (500 nM) or LDN21 (500 nM). Daily 6-hour pulses of parathyroid hormone-related peptide (PTHrP[1-34], 2.5 nM, from day 7) served as potent antihypertrophic control treatment. Day 28 samples were subcutaneously implanted into immunodeficient mice. RESULTS: All groups underwent strong chondrogenesis, but GAG/DNA deposition and ACAN expression were slightly but significantly reduced by ALK inhibition compared to solvent controls along with a mild decrease of the hypertrophy markers IHH-, SPP1-mRNA, and Alkaline phosphatase (ALP) activity. When corrected for the degree of chondrogenesis (COL2A1 expression), only pulsed PTHrP but not ALK1/2/3 inhibition qualified as antihypertrophic treatment. In vivo, all subcutaneous cartilaginous implants mineralized within 8 weeks, but PTHrP pretreated samples formed less bone and attracted significantly less haematopoietic marrow than ALK1/2/3 inhibitor groups. CONCLUSIONS: Overall, our data show that BMP-ALK1/2/3 inhibition cannot program mesenchymal stromal cells toward stable chondrogenesis. BMP-ALK1/2/3 signalling is no driver of hypertrophic MSC misdifferentiation and BMP receptor induction is not an adverse prohypertrophic side effect of TGF-ß that leads to endochondral MSC misdifferentiation. Instead, the prohypertrophic network comprises misregulated PTHrP/hedgehog signalling and WNT activity, and a potential contribution of TGF-ß-ALK4/5-mediated SMAD1/5/9 signalling should be further investigated to decide about its postulated prohypertrophic activity. This will help to successfully engineer cartilage replacement tissues from MSCs in vitro and translate these into clinical cartilage regenerative therapies.

Effects of decongestion on nasal cavity air conditioning efficiency: a CFD cohort study.

Decongestion reduces blood flow in the nasal turbinates, enlarging the airway lumen. Although the enlarged airspace reduces the trans-nasal inspiratory pressure drop, symptoms of nasal obstruction may relate to nasal cavity air-conditioning. Thus, it is necessary to quantify the efficiency of nasal cavity conditioning of the inhaled air. This study quantifies both overall and regional nasal air-conditioning in a cohort of 10 healthy subjects using computational fluid dynamics simulations before and after nasal decongestion. The 3D virtual geometry model was segmented from magnetic resonance images (MRI). Each subject was under two MRI acquisitions before and after the decongestion condition. The effects of decongestion on nasal cavity air conditioning efficiency were modelled at two inspiratory flowrates: 15 and 30 L min-1 to represent restful and light exercise conditions. Results show inhaled air was both heated and humidified up to 90% of alveolar conditions at the posterior septum. The air-conditioning efficiency of the nasal cavity remained nearly constant between nostril and posterior septum but dropped significantly after posterior septum. In summary, nasal cavity decongestion not only reduces inhaled air added heat by 23% and added moisture content by 19%, but also reduces the air-conditioning efficiency by 35% on average.

Obesity Portends Increasing Rates of Superficial Surgical Site Infection Following Pediatric Reduction Mammoplasty: A National Surgical Database Analysis.

INTRODUCTION: Pediatric reduction mammoplasty has become increasingly common due to the obesity epidemic. While obesity remains the leading cause of macromastia leading to surgery, it may also be a risk factor for postoperative complications. This study examines the safety of pediatric reduction mammoplasty and the risk of obesity for complications following this procedure. METHODS: The American College of Surgeons National Surgical Quality Improvement Program Pediatrics was queried to obtain all reduction mammoplasty cases from 2012 to 2020. Univariate and multivariate logistic regression analyses controlling for confounders were carried out to assess the relationship between body mass index (BMI) and rates of complication. RESULTS: One thousand five hundred eighty-nine patients with the primary Current Procedural Terminology code 19318 were included in the final analysis. The mean age was 16.6 (SD, 1.1) years, and the mean BMI was 30.5 (SD, 6.2) lb/in2. Notably, 49% of the patients were obese, and 31% were overweight, while only 0.4% were underweight. Forty-three patients (2.7%) sustained a superficial surgical site infection (SSI) postoperatively. Other complications were less prevalent, including deep SSI (4 patients, 0.3%), dehiscence (11, 0.7%), reoperation (21, 1%), and readmission (26, 1.6%).Independent variables analyzed included age, sex, BMI, diabetes mellitus, American Society of Anesthesiologists (ASA) class, and operative time, of which only BMI and ASA class were found to be significantly associated with SSI on univariate analysis. On multivariate logistic regression while controlling for ASA class and the false discovery rate, there was a strong association between increasing rates of superficial SSI and increasing BMI (unit odds ratio, 1.05; 95% confidence interval, [1.01, 1.09]; P = 0.02). The OR indicates that for each 1-unit increase in BMI, the odds of SSI increase by 5%. CONCLUSIONS: Complications following pediatric reduction mammoplasty are uncommon, demonstrating the safety of this procedure. High BMI was found to have a significantly higher risk for superficial SSI. Increased caution and infection prophylaxis should be taken when performing this operation on obese patients.

Gestational gigantomastia complicated by pseudo-angiomatous stromal hyperplasia - a multidisciplinary management approach.

SUMMARY: Gestational gigantomastia is a rare condition typified by disproportionate bilateral breast enlargement in pregnant women, resulting in skin thinning, ulceration, and bleeding. Less than sixty cases have been documented worldwide, and only one other in South Africa. Pseudo-angiomatous stromal hyperplasia (PASH) is a rare benign proliferation of stromal tissue in a tumorous or diffuse pattern. This, to the best of our knowledge, is the first published case, a 27-year-old human immunodeficiency virus (HIV) positive woman, to present with both conditions concurrently. Medical management with cabergoline was initiated and, seven months post-delivery, a novel Goldilocks mastectomy was performed with acceptable outcomes.

Transgenic Overexpression of HDAC9 Promotes Adipocyte Hypertrophy, Insulin Resistance and Hepatic Steatosis in Aging Mice.

Histone deacetylase (HDAC) 9 is a negative regulator of adipogenic differentiation, which is required for maintenance of healthy adipose tissues. We reported that HDAC9 expression is upregulated in adipose tissues during obesity, in conjunction with impaired adipogenic differentiation, adipocyte hypertrophy, insulin resistance, and hepatic steatosis, all of which were alleviated by global genetic deletion of Hdac9. Here, we developed a novel transgenic (TG) mouse model to test whether overexpression of Hdac9 is sufficient to induce adipocyte hypertrophy, insulin resistance, and hepatic steatosis in the absence of obesity. HDAC9 TG mice gained less body weight than wild-type (WT) mice when fed a standard laboratory diet for up to 40 weeks, which was attributed to reduced fat mass (primarily inguinal adipose tissue). There was no difference in insulin sensitivity or glucose tolerance in 18-week-old WT and HDAC9 TG mice; however, at 40 weeks of age, HDAC9 TG mice exhibited impaired insulin sensitivity and glucose intolerance. Tissue histology demonstrated adipocyte hypertrophy, along with reduced numbers of mature adipocytes and stromovascular cells, in the HDAC9 TG mouse adipose tissue. Moreover, increased lipids were detected in the livers of aging HDAC9 TG mice, as evaluated by oil red O staining. In conclusion, the experimental aging HDAC9 TG mice developed adipocyte hypertrophy, insulin resistance, and hepatic steatosis, independent of obesity. This novel mouse model may be useful in the investigation of the impact of Hdac9 overexpression associated with metabolic and aging-related diseases.