Fat Tissue Research Articles

The Effects of Concentrate Supplement Levels on Feed Utilization and Red Meat Production of Blackhead Somali Sheep Fed Natural Pasture Grass Hay as a Basal Diet.

In recent years, consumers have become aware of their health, and their preference has been rapidly changing to consume less fatty meat. Therefore, devising a strategy to produce lean meat is a concern in this study. One of the strategies, among others, for lean meat production is controlling the amount of supplements given to sheep. Hence, muscle (lean) and adipose tissue (fat) require different amounts of energy to lie down. This study was conducted to evaluate the effects of concentrate supplementation levels on feed utilization and red meat production in Blackhead Somali sheep (BHS) fed natural pasture grass hay as a basal diet. A total of 16 BHS sheep weighing 19.5±0.2kg (mean±SE) at the beginning of the experiment were kept for 90 days by feeding two levels (1% [T1] and 1.75% [T2] body weight [BW] of sheep) of supplement. The sheep were blocked according to their initial BW (IBW), and the supplements were randomly assigned within a block. At the end of the feeding period, all sheep were slaughtered, and carcass and non-carcass data were recorded. Data were analysed using the SAS software version 9.1 of PROC GLM programme. Sheep fed T1 and T2 consumed 6.1 and 8.2MJ/day metabolizable energy (ME), respectively, and 73.1 and 93.6g/day crude protein (CP), in that order. Consequently, sheep fed T2 produced 1.37kg extra BW by growing an average rate of 15g/day greater (p<0.0001) over their counterpart fed T1. They also produced 0.9kg, 0.8 cm2 and 2.64% heavier carcasses, a wider rib eye area and a higher intramuscular fat content (p<0.0001), respectively, over the sheep fed T1. On the other hand, the lean-to-fat ratio was significantly lower in sheep fed T2 than T1. In most parameters considered in this study, sheep fed T2 (1.75% BW) were superior, but its intramuscular fat (IMF) content was much higher than the limit that the consumers needed. Therefore, it can be concluded that 1% BW supplementation is enough for BHS to produce lean meat containing the optimal fat content in stall feeding condition.

ACUTE TOXICITY OF 5-((5-BROMOFURAN-2-YL)-4-METHYL-3-THIOHEPTYL)-1,2,4-TRIAZOLE

Statistical data show that more than 130,000 people in Ukraine are diagnosed with cancer every year. Cancer can affect any organ and eventually the whole body. In most cases, cancer is a tumor affecting epithelial, mucous, muscle, fat, and bone tissues. Also, processes related to malignant formations can occur in the blood and lymph. The main mechanism that triggers the process of formation of neoplasms is a violation of growth and, accordingly, cell division. They begin to grow uncontrollably, multiply, and can also migrate, spreading to nearby tissue structures, and later degenerate into atypical (malignant) ones. Cancer is one of the most life-threatening diseases. Literature data show that more than 90% of cancer patients die due to chronic metastases. Cancer therapy involves the use of drugs that block the growth and spread of cancer cells by affecting certain molecular structures involved in the growth, progression, and spread of cancer. The diversity of the use of means for cancer therapy, namely, hormone therapy, the use of angiogenesis inhibitors and apoptosis inducers, has provided scientists with various options for finding effective means to fight this disease. Heterocyclic compounds are the most common among organic substances. All of them are of natural or synthetic origin and play an extremely important role in human life. A scientifically proven fact today is the high biological activity of 1,2,4-triazole derivatives, they are also used as plasticizers for plastics, anti-corrosion agents, additives to various types of fuels, plant protection agents, etc. Derivatives of 1,2,4-triazole are well known as biologically active compounds, some of them are active substances of medicines. Scientists in many countries of the world are studying the properties of 1,2,4-triazole derivatives. The spectrum of pharmacological activity of 1,2,4-triazoles is wide enough, which allows scientists to choose different directions of research tests. It is also known that 1,2,4-triazole derivatives are low-toxic or practically non-toxic compounds. Studying the toxicity of biologically active molecules is a primary task on the way to their introduction into practical medicine. It was previously established that 5-((5-bromofuran-2-yl)-4-methyl-3-thioheptyl)-1,2,4-triazole has anticancer activity, acting selectively and purposefully on cancer cells. Therefore, it was necessary to investigate the acute toxicity of 5-((5-bromofuran-2-yl)-4-methyl-3-thioheptyl)-1,2,4-triazole by the method of experimental research and using computer technologies. Materials and methods. To achieve this aim, we used both classical and modern methods. Timely well-known methods for computer prediction of acute toxicity GUSAR (Germany), ProTox 3.0 (Germany), TEST (USA) and pkCSM (Australia). To obtain more reliable results, we also used the V. B. Prozorovsky express method in vivo on white nonlinear rats. Results. The data obtained for predicting acute toxicity using all four computer services have similar values. It should also be noted that the experimental results correspond to the obtained non-experimental data. Therefore, the compound 5-((5-bromfuran-2-yl)-4-methyl-3-thioheptil)-1,2,4-triazole can be attributed to the fourth class of toxicity according to the classification of K. K. Sydorov. Conclusions. According to generalized data, the compound 5-((5-bromfuran-2-yl)-4-methyl-3-thioheptil)-1,2,4-triazole has an LD50 value of 1245 mg/kg and is a low-toxic substance.

Uncovering underlying cause for heart failure in a 51-year-old woman with fibromuscular dysplasia

Abstract Introduction/Objective Arrhythmogenic cardiomyopathy is a rare disorder characterized by the replacement of the myocardium with fibroadipose tissue, usually affecting the right ventricle and rarely affecting the left. Methods/Case Report We present the case of a 51-year-old woman with past medical history including fibromuscular dysplasia of the internal carotid arteries and suspected ischemic cardiomyopathy with reduced ejection fraction awaiting heart transplant. The patient suffered a spontaneous coronary artery dissection eight years prior, which was the inciting factor that led to the decline in her cardiac function. After transplant, gross examination of the explanted heart showed a moderate amount of epicardial fat and visible intramural ventricular adipose tissue deposits in the myocardium. On histology, both the right and left ventricle walls showed extensive microscopic fatty infiltration along with focal involvement of the interventricular septum. These findings supported the final diagnosis of arrhythmogenic cardiomyopathy of the right and left ventricle, as well as involvement of the interventricular septum making this case especially rare. There were no signs of infarct or ischemic damage, contrary to what was expected given her diagnosis of ischemic cardiomyopathy. Results (if a Case Study enter NA) NA Conclusion The pathological work-up of this case shed light on the true nature of the patient’s cardiomyopathy and has prompted further genetic testing, as arrhythmogenic cardiomyopathy can be caused by several different genetic mutations. In addition to this work-up, a thorough literature review was performed looking for connections between arrhythmogenic cardiomyopathy and fibromuscular dysplasia, as arrhythmogenic cardiomyopathy is not often seen in this setting. Although no direct connection between the two was uncovered, it was found in the literature that a polymorphism in the Phosphatase and Actin Regulator 1 (PHACTR1) gene has been identified as a genetic component of fibromuscular dysplasia. This variant has been linked to spontaneous coronary artery dissection, which our patient experienced at the young age of 43. This could prompt further genetic investigation into her fibromuscular dysplasia in addition to the genetic work up already being done for her arrhythmogenic cardiomyopathy. This case highlights how rare etiologies can be uncovered through diligent histological analysis, and how further analysis using laboratory techniques such as genetic testing can help patients understand the full breadth of their conditions.

Proteome Expression Signatures: Differences between Orbital and Subcutaneous Abdominal Adipose Tissues.

Differences between orbital and subcutaneous abdominal fat in the same patient have been noted but not formally investigated, previously. The objective of this research was to compare the differential expression of protein profiles in subcutaneous abdominal and orbital adipose tissues. In this cross-sectional, observational study, orbital fat tissue was sampled from 10 patients who underwent blepharoplasty and agreed to provide a small sample of subcutaneous abdominal fat. Shotgun mass spectrometry was performed on the extracted proteome. Data were analyzed using protein appearance patterns, differential expression and statistical enrichment. Protein analysis revealed significant differences in proteomics and differential expression between the orbital and subcutaneous abdominal adipose tissues, which presented five proteins that were uniquely expressed in the orbital fat and 18 in the subcutaneous abdominal fat. Gene Ontology analysis identified significantly different cellular processes and components related to the extracellular matrix or basement membrane components. This analysis shows the differences between orbital and subcutaneous abdominal fat found in proteomics differential expression, uniquely expressed proteins, and cellular processes. Further research is needed to correlate specific proteins and cellular processes to the mechanism of fat accumulation and obesity.

Congenital Appendiceal Atresia: An Extremely Rare Disorder Presenting with Acute Abdomen

Abstract Introduction/Objective Congenital malformations of the appendix are extremely rare and difficult to diagnose preoperatively. One of those anomalies include congenital appendiceal atresia (CAA) which mimics acute appendicitis and is usually ignored in the differentials of acute abdomen. Herein, we present a case study of congenital appendiceal atresia associated with periappendicitis. Methods/Case Report A 62-year-old female with past history of diverticulitis presented with complaints of crampy, diffuse and progressive lower abdominal pain and nausea for two days. She denied fevers, chills or change in bowel movements. Physical examination revealed vitally stable patient with soft, non-distended and tender abdomen in bilateral lower quadrants, worse on the right side and showing positive rebound test. Her complete blood count and chemistry were within normal limits. A computerized tomography arterial portography (CTAP) scan with contrast demonstrated inflammatory stranding around the appendix without abscess, concerning for acute appendicitis. She then underwent laparoscopic appendectomy. Grossly, the appendix consisted of a cylindrical portion of yellow-pink fatty tissue covered by peritoneum measuring 6.2 x 3.3 x 0.5 cm. The peritoneal surface displayed patchy fibrinous exudates. Sectioning revealed yellow adipose tissue with no identifiable appendix. Microscopically, the entire specimen demonstrated a poorly formed, mainly fatty appendix without a discernible lumen or submucosal lymphoid tissue. There were scattered sparsely distributed non-continuous bundles of smooth muscle (muscularis propria) at the periphery, which were highlighted by desmin and trichrome stains. This atretic appendix, mesoappendix and peritoneal covering were acutely inflamed. The final diagnosis was poorly formed, acutely inflamed fatty appendix consistent with congenital appendiceal atresia with accompanying acute periappendicitis. Results (if a Case Study enter NA) NA Conclusion This case would add to the very limited existing literature for congenital appendiceal anomalies and highlight the importance of thorough surgical intraoperative abdominal exploration and submission of the entire specimen for microscopic examination in order to render a definitive diagnosis.

A RANDOMIZED, OPEN LABELLED, CONTROLLED EQUIVALENCE PILOT DRUG TRIAL TO EVALUATE EFFECT OF POLYHERBAL FORMULATIONS, EFFICACY AND SAFETY OF MODIFIED PANCHAKARMA TREATMENT PLAN OBETOX IN PATIENTS WITH OBESITY (MEDOROG).

A chronic complex diseases with excessive fat deposition is called as Obesity. It an lead to many metabolic disease like Type II diabetes, heart diseases, thyroid, hypertension, increased bloos cholesterol level, liver disease, sleep apnoea and certain cancers. It can lead to increase the risk of co morbid conditions specially heart diseases. Weight loss can improve or prevent many health issues related to Obesity. Ayurveda says that Obesity is Vikrita Vriddhi (Abnormal increase) of Medodhatu (Fatty Tissue).Aims and Objective- This study was planned to evaluate the efficacy of Ayurvedic treatment Tab Mednil, Tab Suhruday &amp; Obetox Treatment Plan in the treatment of Obesity (Medorog) and to assess the change in various biochemical markers.Method- This is a proof-of-concept study in which a sample size of 60 participants (30 in each group) was considered sufficient to achieve the study objectives. Participants were randomly assigned to two groups according to a computer-generated randomization list.Results- The results show that participants observed a lighter body image, more energy and enthusiasm, and a reduction in obesity-related complications, in terms of weight, H/W ratio, BMI and lipid profile.Conclusion- Obetox protocol along with herbal remedies gives significant results in the Obesity.

Differential circRNA Screening and Identification of Subcutaneous Fat Tissue in Plateau-type Yaks under Different Feeding Methods

Background: In order to explore the differential expression of circular RNA (circRNA) in the subcutaneous fat tissue of Qinghai yaks under different feeding methods during the dry grass period and its regulatory mechanism. Methods: The present study adopted Illumina sequencing technology to sequence the transcriptome of subcutaneous fat tissue of Qinghai yaks naturally grazed and fattened by housed feeding during the dry grass period and used bioinformatics software to screen out the differentially expressed. The circRNAs were screened for differential expression using bioinformatics software. circRNAs related to fat metabolism were screened by GO function and KEGG pathway enrichment analysis of their source genes and three differentially expressed circRNAs were randomly screened and the expression of the circRNAs was verified by real-time fluorescence quantitative PCR (qRT-PCR). Result: Transcriptome sequencing results showed that a total of 628 differentially expressed circRNAs were obtained, of which 219 were up-regulated and 409 were down-regulated. GO functional enrichment analysis showed that the circRNAs in the free-grazing group originated from genes for major molecular constructs, cellular parts, organs, bioregulation and cellular processes, etc. KEGG pathway enrichment analysis showed that the circRNAs could be participate in signaling pathways such as phagosomes, protein digestion and absorption. qRT-PCR results showed that the expression levels of the three circRNAs were consistent with the sequencing results and the sequencing results were accurate and reliable. This experiment provides a molecular basis for further understanding of fat metabolism in yaks.

Effects of Environmental Noise Stress on Mouse Metabolism

Environmental noise is associated with various health outcomes. However, the mechanisms through which these outcomes influence behavior and metabolism remain unclear. This study investigated how environmental noise affects the liver, adipose tissue, and brain metabolic functions, leading to behavioral and body weight changes. Mice were divided into a noise group exposed to construction noise and an unexposed (control) group. Behavior and body weight changes were monitored over 50 days. Early changes in response to noise exposure were assessed by measuring plasma cortisol and glial fibrillary acidic protein expression in brain tissues on days 1, 15, and 30. Chronic responses, including changes in lipoprotein and fat metabolism and neurotransmitters, were investigated by analyzing serum lipoprotein levels and body fat mass and evaluating liver, fat, and brain tissue after 50 days. The noise group showed higher locomotor activity and reduced anxiety in the open-field and Y-maze tests. Noise exposure caused an initial weight loss; however, chronic noise increased fat mass and induced adipocyte hypertrophy. Our findings underscore the role of environmental noise-induced stress in augmenting locomotor activity and reducing anxiety in mice through neurotransmitter modulation while increasing the risk of obesity by decreasing HDL cholesterol levels and promoting adipocyte hypertrophy.

The Assessment of Anthropometric Measures and Changes in Selected Biochemical Parameters in Obese Children in Relation to Blood Lead Level.

Our paper draws attention to the impact of lead (Pb) on the specificity of obesity development in children exposed to environmental pollution. An advantage of this paper is the homogeneous study group comprising children of identical age from a single geographic region. Moreover, while the influence of environmental toxins on adults has been extensively explored, this study delves into pediatric populations, which have yet to receive comprehensive scrutiny within the scientific literature. Initially, a group of 136 obese children (the research program lasted three consecutive years: 2016, 2017, and 2018) living in the north-western region of Poland, from whom biochemical tests and auxological data were obtained, were enrolled for analysis. Blood lead levels (BLLs) were determined in 115 children. The age of the children ranged from 7.1 to 10.4 years. The body mass index (BMI) of children averaged 21.5 ± 2.2. The results showed that a large proportion of the participants had BLLs above the threshold for Pb. BLLs ≤ 5 µg/dL (considered safe for children and pregnant women) were found in over 70% of the participants, with BLLs in the range of 5.01-10.00 µg/dL in over 26% of the children, and concentrations > 10 µg/dL (considered toxic threshold for adults) in nearly 2% of the children. The results of our research revealed a positive association between BLLs and average systolic and diastolic blood pressure in the studied children. Moreover, we found a negative correlation between BLLs and absolute fat tissue content and triglyceride concentration. Among the included biochemical factors, only insulin demonstrated a statistically significant relationship with fat mass. This result suggests that early carbohydrate metabolism disorders in overweight children involve decreased peripheral tissue insulin sensitivity. Lead exposure may significantly contribute to the development of hypertension, insulin resistance, and glucose metabolism disorders in overweight and obese children. It is essential to implement multidirectional actions to increase awareness of the harmful effects of xenobiotic exposure, including lead, in order to prevent early-life exposure.

New Insight for Enhanced Topical Targeting of Caffeine for Effective Cellulite Treatment: In Vitro Characterization, Permeation Studies, and Histological Evaluation in Rats

Cellulite (CLT) is one of the commonly known lipodystrophy syndromes affecting post-adolescent women worldwide. It is topographically characterized by an orange-peel, dimpled skin appearance hence, it is an unacceptable cosmetic problem. CLT can be modulated by surgical procedures such as; liposuction and mesotherapy. But, these options are invasive, expensive and risky. For these reasons, topical CLT treatments are more preferred. Caffeine (CA), is a natural alkaloid that is well-known for its prominent anti-cellulite effects. However, its hydrophilicity hinders its cutaneous permeation. Therefore, in the present study CA was loaded into solid lipid nanoparticles (SLNs) by high shear homogenization/ultrasonication. CA-SLNs were prepared using Compritol® 888 ATO and stearic acid as solid lipids, and span 60 and brij™35, as lipid dispersion stabilizing agents. Formulation variables were adjusted to obtain entrapment efficiency (EE > 75%), particle size (PS < 350 nm), zeta potential (ZP < −25 mV) and polydispersity index (PDI < 0.5). CA-SLN-4 was selected and showed maximized EE (92.03 ± 0.16%), minimized PS (232.7 ± 1.90 nm), and optimum ZP (−25.15 ± 0.65 mV) and PDI values (0.24 ± 0.02). CA-SLN-4 showed superior CA release (99.44 ± 0.36%) compared to the rest CA-SLNs at 1 h. TEM analysis showed spherical, nanosized CA-SLN-4 vesicles. Con-LSM analysis showed successful CA-SLN-4 permeation transepidermally and via shunt diffusion. CA-SLN-4 incorporated into Noveon AA−1® hydrogel (CA-SLN-Ngel) showed accepted physical/rheological properties, and in vitro release profile. Histological studies showed that CA-SLN-Ngel significantly reduced mean subcutaneous fat tissue (SFT) thickness with 4.66 fold (p = 0.035) and 4.16 fold (p = 0.0001) compared to CA-gel, at 7th and 21st days, respectively. Also, significant mean SFT thickness reduction was observed compared to untreated group with 4.83 fold (p = 0.0005) and 3.83 fold (p = 0.0043), at 7th and 21st days, respectively. This study opened new avenue for CA skin delivery via advocating the importance of skin appendages. Hence, CA-SLN-Ngel could be a promising nanocosmeceutical gel for effective CLT treatment.Graphical

Strangulation

Detection of manual strangulation, choking and hanging, as well as the intensity of these actions, helps to clarify the course of events, to enforce the state's right to prosecute and ultimately to protect against further attacks. However, this is complicated by the scarcity of externally visible findings. The forensic examination of the head and neck after strangulation is carried out by means of external inspection to detect injuries and congestion above the strangulation level. Lesions below the surface of the skin, in particular of the subcutaneous fat tissue, the muscles or the laryngeal structures, usually escape the external inspection. Imaging techniques allow internal injuries to be recorded and objectified, which can be of considerable added value in the collection of evidence. Since criminal proceedings must meet the highest standards of security, high demands are placed on imaging and diagnosis. Imaging techniques are suitable for detecting and objectifying internal injuries after aperson has survived strangulation. However, their excellent reconstruction and visualization capabilities also make them avaluable addition to postmortem examinations. After reported and survived strangulation, choking or hanging, magnetic resonance imaging (MRI) of the soft tissues of the neck should be performed as soon as possible, and if cerebral damage is suspected, the skull should also be examined. If the event was not survived, whole-body computed tomography (CT) is now standard practice at many forensic medicine institutes.

Abundance, habitat distribution and content of reserve energy substances in shrews (Sorex caecutiens, Sorex isodon) within the Seymchan-Buyundinskaya Depression (Upper Kolyma River region)

This research examined the influence of interspecific interactions among shrew species on their territorial distribution and trophic conditions within larch and poplar-chosenia forests along the upper Kolyma River. The study specifically analyzed the biotopic characteristics associated with the relative abundance and energy reserve content, including fat tissue mass and glycogen levels in the liver, of Sorex caecutiens and S. isodon. Fieldwork was conducted in the Seymchan- Buyunda depression during July and August in 2003 and 2010. A total of 1,588 individuals from both species were captured using pitfall traps. The assessment of energy reserve content in S. caecutiens (n = 736) and S. isodon (n = 113) was carried out between 2006 and 2010. The abundance of S. caecutiens in the examined habitats exhibited consistent trends and a strong correlation (RS = 0.95, p &lt; 0.01). Conversely, S. isodon displayed asynchronous fluctuations in abundance across various habitats, likely attributable to competition with Laxmann’s shrew, which tends to displace S. isodon from its preferred larch forest during periods of elevated population density. The interannual variations in energy reserve content for both shrew species were remarkably similar, with no significant differences observed between habitats. The nature of these variations suggested insufficient feeding conditions for the animals during years of high overall abundance, with the dominant species, S. caecutiens, contributing most significantly to this phenomenon in both habitats of the upper Kolyma. The results indicate that interspecific relationships play a crucial role in shaping both territorial distribution and food availability for these shrew species.

Fresh Human Umbilical Cord Arteries as a Potential Source for Small-Diameter Vascular Grafts.

The demand for small-diameter vascular grafts has been globally increased but still lacks optimal solutions in this category. This study evaluated the feasibility of utilizing human pretreated fresh and nondecellularized umbilical cord arteries (hUCAs) as vascular grafts without needing any immunosuppression process. A mixed lymphocyte reaction assay revealed that hUCAs did not induce lymphocyte proliferation or cytokine production. To assess the in vivo inflammatory response, hUCAs were buried in fatty tissue under the skin of the abdominal wall in the left and right iliac fossas of rats. The average sizes of the implanted hUCAs remained consistent at 30 days post implantation. To evaluate xenogeneic transplantation, hUCAs were grafted to the abdominal aorta below the kidney of Wister rats. Remarkably, all rats exhibited positive revascularization and perfusion, maintaining blood pressure values of around 110/70 mmHg. Doppler ultrasound consistently indicated good circulation, with the three separate echogenic layers corresponding to the three arterial wall layers throughout the assessment period. Grafted rats exhibited normal motor behavior, accompanied by positive responses to thermal and pain stimulation. Blood biochemical values and whole blood cell counts showed no significant differences between pre and post-transplantation. Histological analysis of the grafts revealed no calcification or thrombosis, and a mild chronic inflammatory response was presented. In conclusion, hUCAs maintained their structural and functional properties after transplantation in rats without immunosuppression. This highlights their potential as a source for allogeneic, readily accessible, small-diameter vascular grafts.

Autophagy Alterations in White and Brown Adipose Tissues of Mice Exercised under Different Training Protocols.

Autophagy is a conserved catabolic process that promotes cellular homeostasis and health. Although exercise is a well-established inducer of this pathway, little is known about the effects of different types of training protocols on the autophagy levels of tissues that are tightly linked to age-related metabolic syndromes (like brown adipose tissue) but are not easily accessible in humans. Here, we take advantage of animal models to assess the effects of short- and long-term resistance and endurance training in both white and brown adipose tissue, reporting distinct alterations on autophagy proteins microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B, or LC3B) and sequestosome-1 (SQSTM1/p62). Additionally, we also analyzed the repercussions of these interventions in fat tissues of mice lacking autophagy-related protein 4 homolog B (ATG4B), further assessing the impact of exercise in these dynamic, regulatory organs when autophagy is limited. In wild-type mice, both short-term endurance and resistance training protocols increased the levels of autophagy markers in white adipose tissue before this similarity diverges during long training, while autophagy regulation appears to be far more complex in brown adipose tissue. Meanwhile, in ATG4B-deficient mice, only resistance training could slightly increase the presence of lipidated LC3B, while p62 levels increased in white adipose tissue after short-term training but decreased in brown adipose tissue after long-term training. Altogether, our study suggests an intricated regulation of exercise-induced autophagy in adipose tissues that is dependent on the training protocol and the autophagy competence of the organism.

Brown adipose tissue: a potential target for aging interventions and healthy longevity.

Brown Adipose Tissue (BAT) is a type of fat tissue that can generate heat and plays an important role in regulating body temperature and energy metabolism. Enhancing BAT activity through medication, exercise and other means has become a potential effective method for treating metabolic disorders. Recently, there has been increasing evidence suggesting a link between BAT and aging. As humans age, the volume and activity of BAT decrease, which may contribute to the development of age-related diseases. Multiple organelles signaling pathways have been reported to be involved in the aging process associated with BAT. Therefore, we aimed to review the evidence related to the association between aging process and BAT decreasing, analyze the potential of BAT as a predictive marker for age-related diseases, and explore potential therapeutic strategies targeting BAT for aging interventions and healthy longevity.

8660 Bodipy Labeled Vitamin D3 Associates With Lipid Droplets In Adipocytes

Abstract Disclosure: N. Ucar: None. J.T. Deeney: None. R. Pickering, PhD: None. M.T. Kirber: None. T. Fan: None. R. Loo, PhD: Research Investigator; Self; Carbogen Amcis BV. M.F. Holick: Grant Recipient; Self; Carbogen Amcis BV. Research Investigator; Self; Carbogen Amcis BV. Obese patients are often found to be deficient in vitamin D, requiring higher levels of supplementation than normal weight subjects. While this has been attributed to vitamin D3‘s lipid solubility and accumulation in fat tissue, little is known about how vitamin D3 enters adipocytes and associates with the intracellular lipid droplet. The goal of this study was to investigate this association using a novel fluorescently labelled vitamin D3. Bodipy, 4,4-difluoro-1,3,5, 7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (BODIPY 493/503), was covalently linked to vitamin D3 and its structure was confirmed by NMR and mass spectroscopy. Murine 3T3L1 and primary adipocytes were used for our study. Mouse 3T3L1 preadipocytes were cultured in multiwell plates or glass bottom dishes in high glucose DMEM media and differentiated for 7-14 days. Primary adipocytes were obtained by collagenase digestion after surgical extraction of adipose tissue from male/female C57BL/6J mice and attached to glass bottom dishes. The cultured adipocytes were exposed to 10 microM BODIPY labelled Vitamin D3 (vitD-B). BODIPY was added to cultured cells and served as the control. Cells were imaged at various times on a wide-field epifluorescence microscope and analysed with NIH ImageJ software. VitD-B adipocyte uptake and accumulation in lipid droplets was observed over 24 hrs. Isolated lipid droplets were also incubated with vitD-B and BODIPY. VitD-B in mature 3T3L1 cells was observed in lipid droplets after 1h incubation and increased fluorescent intensity was observed over the next 24 hrs. BODIPY was observed in the lipid droplets after 15-20 mins. As a negative control, non-differentiated 3T3L1 cells did not exhibit staining by BODIPY even after 24-hrs. When vitD-B was added to primary cultured adipocytes, it appeared in the adipocytes within 1-hr. Fluorescence intensity of primary adipocytes was increased 1.2-fold at 8 hrs and 5.7-fold at 24 hrs compared to 1 hr. For comparison the positive control treated with BODIPY exhibited rapid fluorescence uptake into primary adipocytes that was increased 29-fold higher than that of vitD-B at 1 hr. VitD-B and BODIPY both demonstrated rapid uptake into isolated lipid droplets (less than 2 min) based on fluorescence microscopy.These results hold promising implications for understanding of the interaction between vitamin D and intracellular lipid droplets. Keywords: Adipocyte, Vitamin D3, BODIPY, adipocytes, lipid droplet, fluorescent labelled vitamin D3 Presentation: 6/2/2024

8631 Tanycytic TSHR Activation Regulates Blood-Hypothalamus Barrier Plasticity, Ingestive Behavior, Adipose Remodeling, and Body Weight

Abstract Disclosure: L. Cullen: None. H.S. Kannangara: None. R. Witztum: None. J. Burgess: None. S. Miyashita: None. A. Gumerova: None. F. Korkmaz: None. S.L. Sims: None. U. Cheliadinova: None. G. Pevnev: None. O. Moldavski: None. O. Barak: None. S. Rojekar: None. V. Laurencin: None. T. Frolinger: None. T. Yuen: None. K. Goosens: None. W. Zhou: None. V. Ryu: None. M. Zaidi: None. The notion that TSH acts solely on its primary endocrine target, the thyroid gland, has long been challenged (Abe et al., 2003; PMID: 14567913). More recently, however, we and others have used single transcript technology to document, for the first time, Tshr expression in over 173 brain regions and nuclei, particularly hypothalamic tanycytes (eLife, 2022, PMID: 36052994). The latter cells are known to convey metabolic information across the blood-hypothalamus barrier (BHB) and regulate energy homeostasis. To study whether tanycytic TSHRs have a role in the regulation of BHB permeability, ingestive behavior, adipose tissue remodeling and body weight, we first compared BHB vascular permeability of food-deprived and ad libitum-fed Tshr+/- mice and their wild type (WT) littermates. Transmission electron microscopy and immunostaining was used to study the expression of the constitutive tight junction protein claudin-1 and the glycoprotein MECA-32, which are expressed in tanycytes and endothelial cells, respectively. In loss-of-function studies, fasting of Tshr+/- mice and of WT mice significantly increased the organization of tanycytic honeycomb pattern of claudin-1 and MECA-32-associated fenestral diaphragms in the median eminence and arcuate nucleus, suggesting decreased BHB permeability. As a result, peanut butter consumption following fasting was decreased significantly compared to control mice. In gain-of-function studies, intracerebroventricular (ICV) infusions of a highly specific TSHR agonist, MS438, profoundly increased BHB permeability in fasted mice, as evidenced by decreased claudin-1 and MECA-32 immunostaining and significant increases in peanut butter consumption. This was associated with greater loss of fat mass and body weight following food deprivation, as well as increased influx of fatty acids across the BHB, increased NPY expression (as a measure of increased appetite), and increased secretion of ghrelin from the stomach fundus. We further performed c-Fos immunostaining in brain centers regulating ingestive behavior. ICV MS438 significantly decreased c-Fos immunoreactivity in the hypothalamic paraventricular nucleus, arcuate nucleus and the nucleus of the solitary tract. Early studies using CRSIPR/Cas9 to delete Tshrs in tanycytes via ICV injection resulted in reduced body weight following food deprivation. Finally, using PRV152 (injected into fat tissue) and PRV614 (injected into stomach fundus), we colocalized immunostaining in the hypothalamic paraventricular nucleus, and hindbrain raphe pallidus. Collectively, these data establish a new role for tanycytic TSHRs in regulating BHB plasticity, ingestive behavior, adipose tissue remodeling, and body weight through a novel fast-forward circuit involving the hypothalamus, stomach fundus and fat depots. Presentation: 6/3/2024

8087 A Case Series on Thyroid Eye Disease Precipitated by the COVID Vaccine in Patients with Long-Standing Primary Hypothyroidism

Abstract Disclosure: R. Hassan: None. J. Islam: None. Background: Thyroid eye disease (TED) is an autoimmune disease characterized by progressive inflammation and damage to the tissues around the eyes, especially extraocular muscle, connective, and fatty tissue. It is most commonly seen in patients with Graves' disease. Less commonly, TED may occur in patients with hypothyroidism. Case Discussion We are presenting a case series on TED precipitated by the COVID vaccine in three patients with known cases of long-standing hypothyroidism. References ranges:TPO Ab: (Ref range: &amp;lt;9.0 IU/mL)TSI: (Ref range: &amp;lt;=1.3 TSI index)TRAb : (Ref range: 0.00-1.75 IU/L)TSH: (Ref range: 0.450-4.500 uIU/mL)Free T4: (Ref range: 0.82-1.77 ng/dL)T3: (Ref range: 87.00 - 178.00 ng/dL) CASE 1: 59 year-old female patient with 18-year history of primary hypothyroidism on levothyroxine who presented with a 5 month history of progressive ocular symptoms of double vision and “puffy eyes” along with other thyrotoxic symptoms. These occurred after receiving her second COVID-19 vaccine. Labs showed elevated TSI and TRAb (3.0, 6.32). TPO antibody was within normal limits at 0.5. Patient had undetectable TSH and free T4 within normal range (162, 1.08). CASE 2: 70 year-old female patient with 25-year history of primary hypothyroidism on levothyroxine who presented with a 4 month history of eye discomfort, eyelid blistering and ocular swelling after she receiving her first dose of COVID-19 vaccine. She was found to have increased ocular pressure per her ophthalmologist. On lab work, she was found to have elevated TSI and TRAb (7.1, 2.60). TPO antibody was within normal limits at 0.8. TSH was undetectable and free T4 were within normal range (159.76, 1.49). CASE 3: 82 year-old female with 30-year history of primary hypothyroidism on levothyroxine who started developing diplopia and proptosis over a 6 month course after she received her first COVID-19 vaccine.Labs showed elevated TSI and TRAb (5.1, 17). Her TPO antibody was within normal limits at 0.4. Her TSH was undetectable, and free T4 was within normal limits (71.76, 1.32). All three patients were started on low-dose methimazole, prednisone, and completed an eight week infusion course of Teprotumumab (Tepezza) with subsequent improvement of proptosis and diplopia. Conclusion Providers should be aware that patients with long standing hypothyroidism, who suddenly require less to no thyroid hormone replacement along with new onset ocular symptoms could be developing TED. This had previously been thought to be solely associated with Graves’ Disease but now has been seen with an uptick in incidence in patients with chronic hypothyroidism during the COVID pandemic. This is likely related to immune response that been associated with vaccines. Presentation: 6/3/2024

12542 Results Of The Foresight Trial Support The Efficacy And Safety Of Once-weekly Lonapegsomatropin In Adults With Growth Hormone Deficiency (ghd)

Abstract Disclosure: B.M. Biller: Consulting Fee; Self; HRA Pharmaceuticals, Novartis Pharmaceuticals, Sparrow, Strongbridge Biopharma. Grant Recipient; Self; Strongbridge Biopharma. A. Gilis-Januszewska: Speaker; Self; Ipsen, Novartis Pharmaceuticals, Novo Nordisk, Recordati, Teva Pharmaceutical Industries Ltd.. M. Doknic: None. A.M. Pico: None. M. Fleseriu: Consulting Fee; Self; Ascendis, GlaxoSmithKline, Johnson &amp;Johnson, Karyopharm, Novo Nordisk, Pfizer, Inc., Pharmacosmos. Research Investigator; Self; Ascendis. G. Raverot: None. A.M. Isidori: None. Y. Takahashi: None. J.M. Garcia: None. J.M. Silverstein: None. I. Bancos: None. E. Huang: Employee; Self; Ascendis Pharma, Inc. J. Kang: Employee; Self; Ascendis Pharma, Inc. A.S. Komirenko: Employee; Self; Ascendis Pharma, Inc. L. Domrzalski: Employee; Self; Ascendis Pharma, Inc. A. Shu: Employee; Self; Ascendis Pharma, Inc. K. Yuen: Advisory Board Member; Self; Amryt, Ascendis, Corcept, Crinetics, Novo Nordisk, Recordati, Strongbridge, Xeris. Grant Recipient; Self; Amryt, Ascendis, Corcept, Crinetics. Speaker; Self; Corcept, Novo Nordisk, Recordati. Background: Adult GHD (aGHD) is characterized by metabolic abnormalities due to insufficient growth hormone (GH) production. Lonapegsomatropin was designed to provide sustained release of unmodified somatropin, with the identical amino acid sequence as endogenous GH, and once-weekly injection reduces the burden of daily GH replacement therapy. MethodsForesiGHt was a randomized, parallel-3-arm, placebo(PL)-controlled (double-blind) and active-controlled (open-label) trial designed to establish the efficacy and safety of lonapegsomatropin in aGHD. It evaluated 259 adults with GHD across 21 countries who were GH treatment-naïve or not treated with GH in the prior year, randomized 1:1:1 to receive lonapegsomatropin, once-weekly PL, or daily somatropin (dGH). Fixed dosing was based on age and oral estrogen intake, and designed to be comparable across lonapegsomatropin and dGH arms. Following a 12-week (w) titration period to target maintenance dose, fixed doses were administered for 26w. ResultsBaseline (BL) characteristics were similar between arms. Lonapegsomatropin demonstrated superiority on the primary efficacy endpoint of change from BL in trunk percent fat at Week 38 vs PL (lonapegsomatropin -1.7% vs PL 0.4%, LS mean difference -2.0%, p &amp;lt; 0.0001) and on the key secondary efficacy endpoints of change from BL in total body lean mass (lonapegsomatropin 1.6 kg vs PL -0.1 kg, LS mean difference 1.7 kg, p &amp;lt; 0.0001) and change from BL in trunk fat mass (lonapegsomatropin -0.5 kg vs PL 0.2 kg, LS mean difference -0.7 kg, p = 0.0053). Mean total exposure and maintenance doses were similar for lonapegsomatropin and dGH arms, with larger changes from BL in average IGF-I SDS mean at Week 38 in the lonapegsomatropin arm (1.4) vs dGH arm (0.5). To assess outcomes at comparable weekly IGF-I exposure, a post-hoc analysis was performed in a subset of participants with average IGF-I SDS ≤1.75 SDS at Week 38. Mean IGF-I SDS for these subsets were similar (lonapegsomatropin -0.1, dGH -0.5), and comparable effects in fat and lean tissue compartments were demonstrated (change from BL in trunk percent fat mean -2.4% and -2.6% respectively; change from BL in total body lean mass mean 1.7 kg and 1.4 kg respectively). In the safety population, the incidence of severe AEs was low (lonapegsomatropin, 3.4%; placebo, 1.2%; dGH, 2.3%) and the incidence of treatment-related AEs was similar (lonapegsomatropin 24.7%, dGH 22.1%). Injection site reaction incidence was low and similar for lonapegsomatropin (4.5%), dGH (5.8%) and placebo (4.8%), and A1c levels remained stable in all treatment arms. ConclusionsThe results of the foresiGHt trial indicate that lonapegsomatropin is a safe, efficacious, and tolerable replacement for endogenous GH. Once-weekly dosing may be impactful for adults with GHD who typically manage multiple other medical therapies. Presentation: 6/3/2024

6963 A Rare Case Presentation of Untreated Congenital Adrenal Hyperplasia with Bilateral Giant Myelolipoma

Abstract Disclosure: F. Omran: None. S. Bromley: None. M. Ilahi: None. M. Zena: None. W. Al-Refaie: None. J. Delto: None. A. Singh,: None. Background: Adrenal myelolipoma is a rare benign neoplasm predominantly composed of mature adipose tissue and intermixed myeloid tissue, often associated with conditions like Congenital Adrenal Hyperplasia. The etiology of this neoplasm is not definitively known although there are numerous hypotheses, including research suggesting that excess ACTH could be responsible for the pathogenesis. Clinical Case: A 40-year-old female with a history of congenital adrenal hyperplasia noncompliant with treatment. She presented with cholelithiasis (s/p laparoscopic cholecystectomy), abdominal imaging revealed incidental finding of a large right retroperitoneal mass. She was noted to have generalized excessive hirsutism in male distribution, small breasts, enlarged clitoris, male body habitus, and amenorrhea after stopping steroids years prior. Laboratory workup showed the following hormonal abnormalities: elevated ACTH (1080 pg/ml), elevated testosterone (243 ng/dl) and free testosterone (31.3 pg/ml), elevated androstenedione (23.431 ng/ml), and low LH (&amp;lt;0.02 miu/ml), low FSH (&amp;lt;0.02 miu/ml). CT abdomen showed right lobulated retroperitoneal mass of 4x14.3x20cm with internal fat and soft tissue components, left lobulated retroperitoneal mass of 13.7x4.7x7.5cm with soft tissue and fat components. CT guided-biopsy showed pathology consistent with adrenal myelolipoma: fatty areas with interspersed hematopoietic tissue components, peripheral rim of normal adrenal cortical tissue. Given the large size of the mass and compressive effects on surrounding organs, patient underwent exploratory laparotomy with resection of right retroperitoneal mass, nephrectomy, and adrenalectomy. Discharged on hydrocortisone and fludrocortisone, instructed to follow up by endocrinologist, always wear medical alert bracelet, and provided with hydrocortisone emergency kit. Conclusion: This case serves as a classic presentation of a rare disease state. Adrenal myelolipomas, a rare benign adrenal neoplasm, have been found in several disorders associated with chronic ACTH hypersecretion including congenital adrenal hyperplasia. Most CAH patients with myelolipomas have untreated or poorly treated CAH. Adrenal myelolipomas that are asymptomatic and &amp;lt;5cm in size are usually monitored if one is certain there is no occult malignancy. If these tumors are symptomatic or &amp;gt;7cm, patients should undergo surgical excision. These patients should be followed by endocrinology. Importantly, further guidelines should be further developed for management. Presentation: 6/3/2024