Fetal Brown Adipose Tissue Research Articles

Omental Hibernoma Revealed by 18 F-FDG PET/CT.

Hibernomas are "pseudolipomas" originating from remnants of fetal brown adipose tissue. These rare benign tumors may occur throughout the body but most commonly in the thigh, shoulder, back, and neck, and are rarely found in the abdominal cavity, retroperitoneum, breast, bones, scrotum, and perirectum. We present a case of a 58-year-old woman with a known mediastinal mass, who was incidentally found to have a very FDG-avid fat-containing lesion in the omentum abutting the stomach. Subsequent endoscopic ultrasound-guided fine-needle aspiration confirmed hibernoma. The review of the literature shows the location is very unusual.

Integrated Analysis of Transcriptome, microRNAs, and Chromatin Accessibility Revealed Potential Early B-Cell Factor1-Regulated Transcriptional Networks during the Early Development of Fetal Brown Adipose Tissues in Rabbits.

In domestic mammals, cold stress decreases the survival rate of newborns and increases the cost of management. Brown adipose tissue (BAT) is the main thermogenic organ for cubs, and well-developed fetal BAT (FBAT) is beneficial for newborns to maintain core temperatures during the first several days of life. However, our knowledge of the epigenetic mechanisms during the early development of FBAT remains largely unknown. Rabbits (Oryctolagus cuniculus) are economically important domestic animals. In this study, a histological analysis shows that the tissue content, thermogenic capacity, and lipid content of FBAT dramatically increases from gestational day 21 (G21) to gestational day 24 (G24) in rabbits. RNA-seq, microRNA-seq (miRNA-seq), and the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) show that many genes, miRNAs, and chromatin-accessible regions (referred to as peaks) were identified as significantly changed from G21 to G24, respectively. The upregulated genes from G21 to G24 were significantly enriched in the mitochondrial metabolism and thermogenesis-related signal pathways. The integrated analysis of transcriptome and chromatin accessibility reveals that the peaks in the promoters have a more regulatory effect than peaks in other genomic elements on the expression of their nearby genes in FBATs. The upregulated genes that are associated with increased chromatin accessibility in the promoter regions are involved in the energy metabolism-related signaling pathways. The genes that have a greater tendency to be regulated by miRNAs than the chromatin accessibility in gene promoters are involved in the apelin, insulin, and endocytosis signaling pathways. Furthermore, genome-wide transcription factor (TF) footprinting analysis identifies early B-cell factor1 (EBF1) as playing a key role during early FBAT development. The carbon metabolism, citrate cycle, and PPAR signaling pathways are significantly enriched by the predicted EBF1-regulated cascade TF-network. In conclusion, our work provides a framework for understanding epigenetics regulatory mechanisms underlying the early development of FBAT and identifies potential TF involved in the early development of FBAT in rabbits.

Effects of dietary supplementation with N-carbamylglutamate on maternal endometrium and fetal development during early pregnancy in Inner Mongolia white cashmere goats.

This study investigated the effects of dietary supplementation with N-carbamylglutamate (NCG) on maternal endometrium and fetal development during early pregnancy of Inner Mongolia white cashmere goats. Forty-eight pregnant Inner Mongolia white cashmere goats (average age 3 years old, average lactation parity 2, and average body weight 43.81 ± 2.66 kg) were randomly allocated to three groups: a basal diet (control group, n = 16), a basal diet plus 0.30-g NCG/d (NCG1 group, n = 16), and a basal diet plus 0.40-g NCG/d (NCG2 group, n = 16). All of the does were housed in individual pens and the NCG treatment was conducted from Days 0 to 90 of pregnancy. At Days 17 and 90 of pregnancy, six representative pregnant does in each group were slaughtered. The current study results demonstrated that maternal NCG administration during early pregnancy effectively increased the arginine family of amino acids and the glucogenic amino acids concentrations and promoted the mRNA expression of osteopontin (OPN), αv and β3 integrins, and endometrial development of Inner Mongolia white cashmere goats. The supplementation improved the fetal brown adipose tissue (BAT) stores and the mRNA expression of UCP-1 and BMP7, thereby helping to the fetal early development.

Imprinted lncRNA Dio3os preprograms intergenerational brown fat development and obesity resistance

Maternal obesity (MO) predisposes offspring to obesity and metabolic disorders but little is known about the contribution of offspring brown adipose tissue (BAT). We find that MO impairs fetal BAT development, which persistently suppresses BAT thermogenesis and primes female offspring to metabolic dysfunction. In fetal BAT, MO enhances expression of Dio3, which encodes deiodinase 3 (D3) to catabolize triiodothyronine (T3), while a maternally imprinted long noncoding RNA, Dio3 antisense RNA (Dio3os), is inhibited, leading to intracellular T3 deficiency and suppression of BAT development. Gain and loss of function shows Dio3os reduces D3 content and enhances BAT thermogenesis, rendering female offspring resistant to high fat diet-induced obesity. Attributing to Dio3os inactivation, its promoter has higher DNA methylation in obese dam oocytes which persists in fetal and adult BAT, uncovering an oocyte origin of intergenerational obesity. Overall, our data uncover key features of Dio3os activation in BAT to prevent intergenerational obesity and metabolic dysfunctions.

Dietary succinate supplementation to maternal mice improves fetal brown adipose tissue development and thermogenesis of female offspring

Succinic acid widely exists in foods and is used as a food additive. Succinate not only serves as an energy substrate, but also induces protein succinylation. Histone succinylation activates gene transcription. The brown adipose tissue (BAT) is critical for prevention of obesity and metabolic dysfunction, and the fetal stage is pivotal for BAT development. Up to now, the role of maternal succinate supplementation on fetal BAT development and offspring BAT function remains unexamined. To test, female C57BL/6J mice (2-month-old) were separated into 2 groups, received with or without 0.5% succinic acid in drinking water during gestation and lactation. After weaning, female offspring were challenged with high fat diet (HFD) for 12 weeks. Newborn, female weanling, and HFD female offspring mice were analyzed. For neonatal and weaning mice, the BAT weight relative to the whole body weight was significantly increased in the succinate group. The expression of PGC-1α, a key transcription co-activator promoting mitochondrial biogenesis, was elevated in BAT of female neonatal and offspring born to succinate-fed dams. Consistently, maternal succinate supplementation enhanced thermogenesis and the expression of thermogenic genes in offspring BAT. Additionally, maternal succinate supplementation protected female offspring against HFD-induced obesity. Furthermore, in C3H10T1/2 cells, succinate supplementation promoted PGC-1α expression and brown adipogenesis. Mechanistically, succinate supplementation increased permissive histone succinylation and H3K4me3 modification in the Ppargc1a promoter, which correlated with the higher expression of Ppargc1a. In conclusion, maternal succinate supplementation during pregnancy and lactation enhanced fetal BAT development and offspring BAT thermogenesis, which prevented HFD-induced obesity and metabolism dysfunction in offspring.

195 Maternal Impact on Fetal Muscle and Adipose Tissue Development

Abstract Tissues and organs are actively developing during the fetal stage, which is sensitive to nutritional alteration and exerts long-term impacts on offspring performance. Both muscle and adipose tissue are derived from the dermomyotome during the early embryonic stage, and their common origins provide an opportunity to promote myogenic instead of adipogenic differentiation, which enhances the lean/fat ratio of offspring. In previous studies with sheep and cattle, we found that maternal nutrient deficiency reduces fetal myogenesis and the lean/fat ratio of offspring. Stress is common in animals during pregnancy, and we examined the impacts of maternal stress induced by dexamethasone on fetal muscle and adipose development. We found that maternal stress impairs fetal muscle and brown adipose tissue (BAT) development. Mechanistically, we found that maternal stress suppresses mitochondrial biogenesis during fetal muscle and BAT development by elevating DNA methylation in the promoter of peroxisome proliferator-activated receptor-gamma coactivator α (PGC-1α), which persists in offspring muscle and BAT, generating lasting effects on the functions of muscle and adipose tissue. In short, available data clearly show that maternal nutrition and other physiological factors have profound impacts on fetal development, which programs offspring performance. Understanding related mechanisms are important for effective and precise management of animals during gestation in order to enhance production efficiency of offspring.

Effects of maternal undernutrition during late pregnancy on the regulatory factors involved in growth and development in ovine fetal perirenal brown adipose tissue.

ObjectiveThe experiment was conducted to evaluate the effects of maternal undernutrition during late pregnancy on the expressions of genes involved in growth and development in ovine fetal perirenal brown adipose tissue (BAT).MethodsEighteen ewes with singleton fetuses were allocated to three groups at day 90 of pregnancy: restricted group 1 (RG1, 0.33 MJ metabolisable energy [ME]/kg body weight [BW]0.75/d, n = 6), restricted group 2 (RG2, 0.18 MJ ME/kg BW0.75/d, n = 6), and a control group (CG, ad libitum, 0.67 MJ ME/kg BW0.75/d, n = 6). The fetuses were removed at day 140 of pregnancy. All data were analyzed by using the analysis of variance procedure.ResultsThe perirenal fat weight (p = 0.0077) and perirenal fat growth rate (p = 0.0074) were reduced in RG2 compared to CG. In fetal perirenal BAT, the protein level of uncoupling protein 1 (UCP1) (p = 0.0001) was lower in RG1 and RG2 compared with CG and UCP1 mRNA expression (p = 0.0265) was decreased in RG2. The protein level of myogenic factor 5 (Myf5) was also decreased in RG2 (p = 0.0001). In addition, mRNA expressions of CyclinA (p = 0.0109), CyclinB (p = 0.0019), CyclinD (p = 0.0015), cyclin-dependent kinase 1 (CDK1) (p = 0.0001), E2F transcription factor 1 (E2F1) (p = 0.0323), E2F4 (p = 0.0101), and E2F5 (p = 0.0018) were lower in RG1 and RG2. There were decreased protein expression of peroxisome proliferator-activated receptor-γ (PPARγ) (p = 0.0043) and mRNA expression of CCAAT/enhancer-binding protein-α (C/EBPα) (p = 0.0307) in RG2 and decreased PPARγ mRNA expression (p = 0.0008) and C/EBPα protein expression (p = 0.0015) in both RG2 and RG1. Furthermore, mRNA expression of bone morphogenetic protein 4 (BMP4) (p = 0.0083) and BMP7 (p = 0.0330) decreased in RG2 and peroxisome proliferator-activated receptor co-activator-1α (PGC-1α) reduced in RG2 and RG1.ConclusionOur observations support that repression of regulatory factors promoting differentiation and development results in the inhibition of BAT maturation in fetal perirenal fat during late pregnancy with maternal undernutrition.

Maternal cold exposure induces distinct transcriptome changes in the placenta and fetal brown adipose tissue in mice

BackgroundBrown adipose tissue (BAT) is specialized to dissipate energy in the form of heat. BAT-mediated heat production in rodents and humans is critical for effective temperature adaptation of newborns to the extrauterine environment immediately after birth. However, very little is known about whether and how fetal BAT development is modulated in-utero in response to changes in maternal thermal environment during pregnancy. Using BL6 mice, we evaluated the impact of different maternal environmental temperatures (28 °C and 18 °C) on the transcriptome of the placenta and fetal BAT to test if maternal cold exposure influences fetal BAT development via placental remodeling.ResultsMaternal weight gain during pregnancy, the average number of fetuses per pregnancy, and placental weight did not differ between the groups at 28 °C and 18 °C. However, the average fetal weight at E18.5 was 6% lower in the 18 °C-group compared to the 28 °C-group. In fetal BATs, cold exposure during pregnancy induced increased expression of genes involved in de novo lipogenesis and lipid metabolism while decreasing the expression of genes associated with muscle cell differentiation, thus suggesting that maternal cold exposure may promote fetal brown adipogenesis by suppressing the myogenic lineage in bidirectional progenitors. In placental tissues, maternal cold exposure was associated with upregulation of genes involved in complement activation and downregulation of genes related to muscle contraction and actin-myosin filament sliding. These changes may coordinate placental adaptation to maternal cold exposure, potentially by protecting against cold stress-induced inflammatory damage and modulating the vascular and extravascular contractile system in the placenta.ConclusionsThese findings provide evidence that environmental cold temperature sensed by the mother can modulate the transcriptome of placental and fetal BAT tissues. The ramifications of the observed gene expression changes warrant future investigation.

Retroperitoneal Hibernoma: Exhibition of Three Case Reports and Literature Review

Hibernoma is a rare benign tumor that becomes from the vestiges of fetal brown adipose tissue. It can be located on different regions of the body, being tight the most frequent. Retroperitoneal region is approximately of 9.4%. The first person to describe this histological type was Merkel. To the present, there are only described 25 cases on this location. It has a slowly growth, so it is normally asymptomatic, and it usually presents doing compression of different structures. To diagnose the MRI is the best prove, although biopsy will provide definite diagnosis describing four possible variants. Immunochemistry of MDM2, CDK4 and p16 genes is really important to do the differential diagnosis with well-differentiated liposarcoma (WDLS). Only one extensive review of hibernoma with 170 cases on different regions is published. But there is no review on literature specifically of retroperitoneal region, so this is the purpose of the current study. Following we present three more cases of retroperitoneal hibernoma that we have treat on our Mesenchymal Tumours Unit and a revision of the previously published.

Water-fat magnetic resonance imaging of adipose tissue compartments in the normal third trimester fetus.

Assessment of fetal adipose tissue gives information about the future metabolic health of an individual, with evidence that the development of this tissue has regional heterogeneity. To assess differences in the proton density fat fraction (PDFF) between fetal adipose tissue compartments in the third trimester using water-fat magnetic resonance imaging (MRI). Water-fat MRI was performed in a 1.5-T scanner. Fetal adipose tissue was segmented into cheeks, thorax, abdomen, upper arms, forearms, thighs and lower legs. PDFF and R2* values were measured in each compartment. Twenty-eight women with singleton pregnancies were imaged between 28 and 38weeks of gestation. At 30weeks' gestation (n=22), the PDFF was statistically different between the compartments (P<0.0001), with the highest PDFF in cheeks, followed by upper arms, thorax, thighs, forearms, lower legs and abdomen. There were no statistical differences in the rate of PDFF change with gestational age between the white adipose tissue compartments (P=0.97). Perirenal brown adipose tissue had a different PDFF and R2* compared to white adipose tissue, while the rate of R2* change did not significantly change with gestational age between white adipose tissue compartments (P=0.96). Fetal adipose tissue accumulates lipids at a similar rate in all white adipose tissue compartments. PDFF variances between the compartments suggest that accumulation begins at different gestational ages, starting with cheeks, followed by extremities, trunk and abdomen. Additionally, MRI was able to detect differences in the PDFF between fetal brown adipose tissue and white adipose tissue.

Embryonic exposure to hyper glucocorticoids suppresses brown fat development and thermogenesis via REDD1

Maternal stress during pregnancy is prevailing worldwide, which exposes fetuses to intrauterine hyper glucocorticoids (GC), programming offspring to obesity and metabolic diseases. Despite the importance of brown adipose tissue (BAT) in maintaining long-term metabolic health, impacts of prenatal hyper GC on postnatal BAT thermogenesis and underlying regulations remain poorly defined. Pregnant mice were administrated with synthetic GC dexamethasone (DEX) at levels comparable to fetal GC exposure of stressed mothers. Prenatal GC exposure dose-dependently reduced BAT thermogenic activity, contributing to lower body temperature and higher mortality of neonates; such difference was abolished under thermoneutrality, underscoring BAT deficiency was the major contributor to adverse changes in postnatal thermogenesis due to excessive GC. Prenatal GC exposure highly activated Redd1 expression and reduced Ppargc1a transcription from the alternative promoter (Ppargc1a-AP) in neonatal BAT. During brown adipocyte differentiation, ectopic Redd1 expression reduced Ppargc1a-AP expression and mitochondrial biogenesis; and the inhibitory effects of GC on mitochondrial biogenesis and Ppargc1a-AP expression were blocked by Redd1 ablation. Redd1 reduced protein kinase A phosphorylation and suppressed cyclic adenosine monophosphate (cAMP) -responsive element-binding protein (CREB) binding to the cAMP regulatory element (CRE) in Ppargc1a-AP promoter, leading to Ppargc1a-AP inactivation. In summary, excessive maternal GC exposure during pregnancy dysregulates Redd1-Ppargc1a-AP axis, which impairs fetal BAT development, hampering postnatal thermogenic adaptation and metabolic health of offspring.

1710-P: Maternal Supplementation of Tetrahydrobiopterin Regulates Differentiation of Fetal Brown Adipose Tissue and Contributes to Offspring Metabolic Health

Brown adipose tissue (BAT) is a key organ that produces heat and dissipates energy, and may be clinically relevant to the treatment of obesity and diabetes. Tetrahydrobiopterin (BH4) is an essential co-factor of tyrosine hydroxylase, a rate-limiting enzyme of catecholamine biosynthesis including that of norepinephrine (NA) and nitric oxide (NO) synthase. Although both NA and NO are well-known factors in BAT differentiation, the role of BH4 in the differentiation of BAT is poorly understood. We investigated the role of BH4 in differentiation of BAT using a mouse model of BH4 deficiency, the Hph-1 mouse. Hph-1 neonatal mice exhibit dysplasia of BAT as well as attenuated thermogenesis-related gene expressions (UCP1, Dio2, Pgc1a) compared with control mice. As differentiation capacity is considered to be at maximum during late gestation, we administered BH4 to fetal Hph-1 mice via placental transfer using intraperitoneal injection to pregnant Hph-1 mice for 6 days just before birth. Maternal BH4 supplementation ameliorated dysplasia of neonatal BAT and restored thermogenesis-related genes expression. Intriguingly, offspring of the maternal BH4-supplementation group showed less weight gain, ameliorated glucose intolerance, and improved cold tolerance after growth under high fat chow diet. We then evaluated the direct effect of BH4 on brown adipocyte differentiation using brown pre-adipocytes isolated from control and Hph-1 mice. Compared with control mice, brown pre-adipocytes from Hph-1 mice showed reduced differentiation capacity, while BH4 supplementation in brown pre-adipocytes from Hph-1 mice ameliorated differentiation capacity nitric oxide-dependently. Taking these findings together, BH4 plays an integral role in the differentiation of BAT, especially in the fetal period, and may represent a novel target for prevention of metabolic disorders such as obesity and diabetes. Disclosure H. Minamino: None. Y. Fujita: None. Y. Oguri: None. T. Goto: None. A. Ohashi: None. F. Furuya: None. N. Isomura: None. T. Kohei: None. Y. Li: None. S. Kawarasaki: None. T. Kawada: None. H. Hasegawa: None. N. Inagaki: Research Support; Self; Astellas Pharma Inc., Drawbridge Health, Japan Tobacco Inc., Kissei Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Life Scan Japan, Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Novo Nordisk Pharma Ltd.,, Sanofi K.K., Sanwa Kagaku Kenkyusho, Terumo Medical Corporation. Speaker’s Bureau; Self; Astellas Pharma Inc., Merck &amp; Co., Inc., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited.

Excessive Glucocorticoids During Pregnancy Impair Fetal Brown Fat Development and Predispose Offspring to Metabolic Dysfunctions.

Maternal stress during pregnancy exposes fetuses to hyperglucocorticoids, which increases the risk of metabolic dysfunctions in offspring. Despite being a key tissue for maintaining metabolic health, the impacts of maternal excessive glucocorticoids (GC) on fetal brown adipose tissue (BAT) development and its long-term thermogenesis and energy expenditure remain unexamined. For testing, pregnant mice were administered dexamethasone (DEX), a synthetic GC, in the last trimester of gestation, when BAT development is the most active. DEX offspring had glucose, insulin resistance, and adiposity and also displayed cold sensitivity following cold exposure. In BAT of DEX offspring, Ppargc1a expression was suppressed, together with reduced mitochondrial density, and the brown progenitor cells sorted from offspring BAT demonstrated attenuated brown adipogenic capacity. Increased DNA methylation in Ppargc1a promoter had a fetal origin; elevated DNA methylation was also detected in neonatal BAT and brown progenitors. Mechanistically, fetal GC exposure increased GC receptor/DNMT3b complex in binding to the Ppargc1a promoter, potentially driving its de novo DNA methylation and transcriptional silencing, which impaired fetal BAT development. In summary, maternal GC exposure during pregnancy increases DNA methylation in the Ppargc1a promoter, which epigenetically impairs BAT thermogenesis and energy expenditure, predisposing offspring to metabolic dysfunctions.

Maternal obesity impairs fetal mitochondriogenesis and brown adipose tissue development partially via upregulation of miR-204-5p

Maternal obesity (MO) predisposes offspring to metabolic disorders, but the mechanisms remain poorly defined. Recent studies emphasize the importance of brown adipose tissue (BAT) in maintaining metabolic health, and MO was recently demonstrated to impair BAT thermogenic function in offspring. The current study aimed to investigate the mechanisms leading to the impairment in fetal BAT development due to MO. Female C57BL/6J mice were fed a control diet or a 60% high-fat diet for 10 weeks, mated and maintained on their respective diets during pregnancy. Fetal tissue was collected at E18.5, the late stage of pregnancy. Fetal BAT contained more triglycerides compared to the control, which was correlated with higher expression of white adipogenic markers. On the other hand, the expression of BAT markers was down-regulated in the MO fetal BAT. Based on RNA-sequencing analyses, genes related to mitochondriogenesis and myogenesis were found to be down-regulated, while those related to white adipocyte differentiation were up-regulated in MO fetal BAT. Because brown adipocytes are derived from myogenic progenitors, the down-regulation of myogenic genes might partially explain hampered brown adipogenesis in MO fetal BAT. Consistently, mitochondrial DNA and mitochondrial biogenesis markers were also down-regulated in MO fetal BAT. MicroRNA-sequencing identified that miR-204-5p expression was elevated in MO fetal BAT. This microRNA targeted the 3′-untranslated regions of PGC1α and Sirt1 mRNA to suppress their expression and impair mitochondriogenesis. In summary, MO impaired fetal BAT development through suppressing myogenesis and brown adipogenesis while enhancing white adipogenic commitment, and inhibited mitochondriogenesis partially through enhancing miR-204-5p expression.

A rare case of adipocytic tumor in subscapular region: hibernoma

Hibernoma is a rare lipomatous tumor of brown fat origin that emerges from remnants of fetal brown adipose tissue. They are encapsulated, yellow-tan colored, painless and benign soft tissue tumors, usually seen in adults and occur with large cells that have acidophilic, granular and vacuolar cytoplasm and centraly nuclei. Our case is a 33-year-old female who had swelling in the subscapular region. Imaging studies depicted a lesion compatible with lipoma. Macroscopic evaluation of the excision specimen revealed brown, tan-yellow colored and hemorrhagic cut surface compatible with fat tissue. In microscopic examination, a tumor composed of cells with vacuolar, granular and eosinophilic cytoplasm, centrally or peripherally localized small, round nuclei, were observed. These cells were stained with immunhistochemical S-100 and were evaluated to be comparable with lipocytes. With these findings, the patient was diagnosed as having hibernoma. We present this case for its rarity, and for the fact that it can be treated with simple excision, and should be kept in mind especially in the differential diagnosis of lesions with high vascularity

Posterior fossa hibernoma: A rare case in unexpected location radiologically mimicking arteriovenous malformation

Abstract Background Hibernomas are rare tumors histologically originate from the fetal brown adipose tissue. Here, we reported the first hibernoma case located in posterior fossa radiologically mimicking arteriovenous malformation (AVM), presenting with abrupt onset of dizziness, and hiccups. This is the first case of hibernoma location in the posterior fossa. Case description A previously well 32-year-old man, presented with a headache for three days and abrupt onset of dizziness, nausea, vomiting, and hiccups. He had left-sided muscle weakness and hypoesthesia. Non-contrast enhanced computed tomography revealed hemorrhagic lesion at the inferoventral portion of the posterior lobe of cerebellum with compression to medulla oblongata with partial obstruction of fourth ventricle. Magnetic Resonance Imaging (MRI) revealed a mass lesion neighbouring at medulla oblongata which had intratumoral large vessels with branching segments. On T1 weighted images the lesion was isointense, on T2 weighted images it was hyperintense. On contrast-enhanced MRI images, heterogeneous contrast pattern was observed which is highly suspicious for AVM. Emergent surgery was performed and total excision was achieved. Histopathological analysis with Hematoxylin and eosin staining revealed yellow coloured, minimal hemorrhagic areas and well-defined encapsulated solid structure. The specimen showed brown adipose tissue content, with well-defined cytoplasm, large granular or multivacuolated cytoplasmic cells. Besides, small groups of univacuolar adipocytes were also observed. The histopathologic diagnosis was typical hibernoma. The postoperative period was uneventful and the patient was discharged in the fourth postoperative day with full neurological recovery. His neurological examination at the sixth postoperative month was completely normal. Radiological evaluation revealed total excision without any recurrence. Conclusions Hibernoma located in the posterior fossa is a unique condition, which may cause acute deterioration of the patient. These lesions may radiologically mimic vascular malformations. The neurological surgeons must kept in mind that hibernoma could also be seen in posterior fossa.

Maternal n-3 PUFA supplementation promotes fetal brown adipose tissue development through epigenetic modifications in C57BL/6 mice

Brown adipose tissue (BAT) is a crucial regulator of energy expenditure. Emerging evidence suggests that n-3 PUFA potentiate brown adipogenesis in vitro. Since the pregnancy and lactation is a critical time for brown fat formation, we hypothesized that maternal supplementation of n-3 PUFA promotes BAT development in offspring. Female C57BL/6 mice were fed a diet containing n-3 PUFA (3%) derived from fish oil (FO), or an isocaloric diet devoid of n-3 PUFA (Cont) during pregnancy and lactation. Maternal n-3 PUFA intake was delivered to the BAT of neonates significantly reducing the n-6/n-3 ratio. The maternal n-3 PUFA exposure was linked with upregulated brown-specific gene and protein profiles and the functional cluster of brown-specific miRNAs. In addition, maternal n-3 PUFA induced histone modifications in the BAT evidenced by 1) increased epigenetic signature of brown adipogenesis, i.e., H3K27Ac and H3K9me2, 2) modified chromatin-remodeling enzymes, and 3) enriched the H3K27Ac in the promoter region of Ucp1. The offspring received maternal n-3 PUFA nutrition exhibited a significant increase in whole-body energy expenditure and better maintenance of core body temperature against acute cold treatment. Collectively, our results suggest that maternal n-3 PUFA supplementation potentiates fetal BAT development via the synergistic action of miRNA production and histone modifications, which may confer long-lasting metabolic benefits to offspring.

De novo reconstruction of human adipose transcriptome reveals conserved lncRNAs as regulators of brown adipogenesis

Obesity has emerged as an alarming health crisis due to its association with metabolic risk factors such as diabetes, dyslipidemia, and hypertension. Recent work has demonstrated the multifaceted roles of lncRNAs in regulating mouse adipose development, but their implication in human adipocytes remains largely unknown. Here we present a catalog of 3149 adipose active lncRNAs, of which 909 are specifically detected in brown adipose tissue (BAT) by performing deep RNA-seq on adult subcutaneous, omental white adipose tissue and fetal BATs. A total of 169 conserved human lncRNAs show positive correlation with their nearby mRNAs, and knockdown assay supports a role of lncRNAs in regulating their nearby mRNAs. The knockdown of one of those, lnc-dPrdm16, impairs brown adipocyte differentiation in vitro and a significant reduction of BAT-selective markers in in vivo. Together, our work provides a comprehensive human adipose catalog built from diverse fat depots and establishes a roadmap to facilitate the discovery of functional lncRNAs in adipocyte development.

Technical note: Isolation and characterization of ovine brown adipocyte precursor cells.

Brown adipose tissue (BAT) plays a critical role in regulating body temperature in newborn lambs. Availability of a stable BAT cell line would be invaluable for biochemical studies to elucidate cellular and molecular mechanisms responsible for nutritional regulation of fetal BAT growth and development. Ovine brown adipocyte precursor cells (BAPC) were isolated from fetal lambs at d 90 of gestation and cultured to establish a stable cell line. These cells were characterized by adipogenic differentiation and expression of a hallmark gene, (). The BAPC doubled every 24 h. After a 9-d induction with a serum-free Dulbecco's modified Eagle Ham/F12 medium, BAPC differentiated into brown adipocytes with large lipid droplets. The differentiation medium induced expression of mRNA and protein in BAPC. Furthermore, after BAPC were passaged 30 times, they maintained similar cell morphology, the potential for adipogenic differentiation, and the ability to express . Taken together, we have established a stable ovine BAPC cell line for studying nutritional regulation of BAT growth and development in the fetus.

The influence of dietary manipulations and gastrointestinal nematodes on twin-bearing merino ewes and determinants of lamb survival

The aim in this experiment was to examine the effects of prepartum supplementation, fat score (FS) and gastrointestinal nematode (GIN) infection on whole-body composition of twin-bearing and rearing Merino ewes. These effects were then related to lamb birth weight, ewe colostrum yield and foetal brown adipose tissue stores as principal determinants of neonatal mortality. The experiment was conducted as a 3×2×2 factorial design from day (d) −98 to weaning at d 55 (relative to the mid-point of lambing, d 0). There were three infection groups (uninfected, 1000 Haemonchus contortus L3/week, or 6000 Trichostrongylus colubriformis L3/week), two levels of nutrition from d −97 to d −52 (designed to achieve FS targets of 2 and 4) and two prepartum supplementation groups (0 or 200g/d cottonseed meal; CSM) from d −52 to d −12. Ewes managed to higher FS during mid-pregnancy were 8kg heavier and 1.3 FS units greater (p<0.001) by d −54, 4kg (p=0.049) and 0.6 FS units (p<0.001) by d −12, but did not differ from low FS ewes by d 53. Carcass fat, omental fat and lean muscle mass (all p<0.001) were greater in high FS ewes at d −12 but not at d 55. Neither colostrum yield, milk yield or lamb birth weight differed between FS groups but lambs born to low FS ewes had greater (p=0.050) brown adipose tissue reserves. Prepartum supplementation increased ewe live weight (p=0.049), carcass fat (p=0.032) and muscle (p=0.013) by parturition and lamb birth weight (p=0.012), with the benefit being greatest for low FS ewes. T. colubriformis infection reduced lamb birth weight and H. contortus reduced ewe live weight, milk yield and lamb growth to weaning. These results highlight the effectiveness of providing adequate nutrition to twin-bearing Merino ewes in late pregnancy and controlling GIN infections, especially where ewe FS has fallen below Australian industry targets.