Islet transplantation into brown adipose tissue can delay immune rejection.

Type 1 diabetes is an autoimmune disease characterized by insulin-producing ß cell destruction. Although islet transplantation restores euglycemia and improves patient outcomes, an ideal transplant site remains elusive. Brown adipose tissue (BAT) has a highly vascularized and antiinflammatory microenvironment. Because these tissue features can promote islet graft survival, we hypothesized that islets transplanted into BAT will maintain islet graft and BAT function while delaying immune-mediated rejection. We transplanted syngeneic and allogeneic islets into BAT or under the kidney capsule of streptozotocin-induced diabetic NOD.Rag and NOD mice to investigate islet graft function, BAT function, metabolism, and immune-mediated rejection. Islet grafts within BAT restored euglycemia similarly to kidney capsule controls. Islets transplanted in BAT maintained expression of islet hormones and transcription factors and were vascularized. Compared with those in kidney capsule and euglycemic mock-surgery controls, no differences in glucose or insulin tolerance, thermogenic regulation, or energy expenditure were observed with islet grafts in BAT. Immune profiling of BAT revealed enriched antiinflammatory macrophages and T cells. Compared with the kidney capsule control, there were significant delays in autoimmune and allograft rejection of islets transplanted in BAT, possibly due to increased antiinflammatory immune populations. Our data support BAT as an alternative islet transplant site that may improve graft survival.

The Effect of TLR Agonists and Myokines on Secretory Activity of Adipogenically Differentiated MSC Cultures.

We studied the effect of bacterial pathogen-associated molecular patterns and myokines on the secretion of adipokines by mesenchymal stem cells (MSC) and products of their adipogenic differentiation. The secretion of adiponectin, adipsin, leptin, and insulin by adipogenically differentiated cell cultures was quantitatively determined using multiplex ELISA. MSC obtained from the stromal vascular fraction of human subcutaneous adipose tissue were shown to secrete a known adipokine adipsin. The ability of white adipocytes to secrete significant amounts of insulin (in vitro) has been shown for the first time. Control cultures of white adipocytes secreted much higher levels of adiponectin, leptin, and insulin when compared to other adipocytes cultures. On the other hand, beige and brown adipocyte cultures secreted more adipsin than white adipocyte cultures. The influence of myokine ß-aminoisobutyric acid on the secretion of adipsin in MSC, white, beige, and brown adipocytes was also studied.

Surgical ablation of whitened interscapular brown fat ameliorates cardiac pathology in salt-loaded metabolic syndrome rats.

Brown adipose tissue (BAT) is an endocrine organ that contributes to thermogenesis and energy consumption. We investigated the effects of salt loading and surgical removal of whitened interscapular BAT (iBAT) on cardiac and adipose tissue pathology in DahlS.Z-Leprfa /Leprfa (DS/obese) rats, an animal model of metabolic syndrome (MetS). DS/obese rats were subjected to surgical removal of iBAT or sham surgery at 8 weeks of age and were provided with drinking water containing or not containing 0.3% NaCl for 4 weeks beginning at 9 weeks of age. Removal of iBAT suppressed the salt-induced exacerbation of left ventricular inflammation, fibrosis, and diastolic dysfunction, but not that of hypertension development, in DS/obese rats. Salt loading attenuated adipocyte hypertrophy but enhanced inflammation in both visceral white adipose tissue (WAT) and iBAT. Although iBAT removal did not affect visceral WAT pathology in salt-loaded DS/obese rats, it attenuated the elevation of circulating interleukin-6 levels in these animals. Downregulation of uncoupling protein-1 expression in iBAT of DS/obese rats was not affected by salt loading. Our results suggest that the conversion of iBAT to WAT-like tissue contributes to a salt-induced elevation of circulating proinflammatory cytokine levels that leads to exacerbation of cardiac pathology in this model of MetS.

Brown Adipose Tissue: A Potential Site for Islet Transplantation.

BACKGROUND: Islet transplantation is a promising treatment in patients with complicated diabetes. The ideal transplant site that can extend islet graft survival and reduce the required number of engrafted islets remains to be established. METHODS: Donor islets were isolated from red fluorescent protein (RFP) mice and transplanted into interscapular brown adipose tissue (BAT) or unilateral inguinal white adipose tissue of age-matched diabetic RFP mice. Blood glucose and body weight of the mice were monitored, and vitality and function of ectopic RFP islets were detected by fluorescence imaging, histological examination, and intraperitoneal glucose tolerance test (GTT). RESULTS: BAT enabled the marginal number of grafted islets (80 islets) to restore blood glucose, insulin level, and GTT to normal values in all diabetic recipient mice in the short term after graft, and maintained these values for 1 year at the end of the experiment. Importantly, in the short term after transplantation, abundant extra- and intraislet neovasculatures were observed in BAT, but not in white adipose tissue, which allowed the ectopic islets to retain typical architecture and morphology and contributed to the normal GTT. Moreover, the islet-engrafted BAT displayed normal structure and morphology without significant immunocyte infiltration, and the recipient mice also showed normal lipid levels in the blood. CONCLUSIONS: BAT remarkably enhances the viability and biological function of the transplanted ectopic islets. Moreover, the anatomical location of BAT lends itself to biopsy, removal, and islet retransplantation, which strongly suggests the BAT as a potential desirable site for islet transplantation in basic and clinical research.

Exendin-4 Improves Diabetic Kidney Disease in C57BL/6 Mice Independent of Brown Adipose Tissue Activation.

BACKGROUND: The role of exendin-4 in brown adipose tissue (BAT) activation was not very clear. This study is to verify the role of BAT involved in renal benefits of exendin-4 in diabetes mellitus (DM). METHODS: In vivo, C57BL/6 mice were randomly divided into nondiabetic (control) and diabetic groups (DM). The diabetic mice were randomized into a control group (DM-Con), BAT-excision group (DM+Exc), exendin-4-treated group (DM+E4), and BAT-excision plus exendin-4-treated group (DM+Exc+E4). The weight, blood glucose and lipids, 24 h urine albumin and 8-OH-dG, and renal fibrosis were analyzed. In vitro, we investigated the role of exendin-4 in the differentiation process of 3T3-L1 and brown preadipocytes and its effect on the rat mesangial cells induced by oleate. RESULTS: The expressions of UCP-1, PGC-1α, ATGL, and CD36 in BAT of DM mice were all downregulated, which could be upregulated by exendin-4 treatment with significant effects on ATGL and CD36. BAT-excision exacerbated high blood glucose (BG) with no significant effect on the serum lipid level. Exendin-4 significantly lowered the level of serum triglycerides (TG) and low-density lipoprotein- (LDL-) c, 24 h urine albumin, and 8-OH-dG; improved renal fibrosis and lipid accumulation; and activated renal AMP-activated protein kinase (AMPK) in diabetic mice regardless of BAT excision. In vitro, there was no significant effect of exendin-4 on brown or white adipogenesis. However, exendin-4 could improve lipid accumulation and myofibroblast-like phenotype transition of mesangial cells induced by oleate via activating the AMPK pathway. CONCLUSIONS: Exendin-4 could decrease the renal lipid deposit and improve diabetic nephropathy via activating the renal AMPK pathway independent of BAT activation.

Brown adipocytes and ß3-stimulant-induced brown-like adipocytes contribute to the prevention of renal crystal formation.

According to recent studies, kidney stones are associated with metabolic syndrome. We focused on brown adipocytes and ß3-stimulant-induced brown-like adipocytes to investigate how these adipocytes influence kidney stone disease. For the interscapular brown adipose tissue (iBAT) removal experiment, mice were subjected to either iBAT removal or sham operation (X-BAT group or sham group), and, after 3 wk, renal crystal deposition was induced by intra-abdominal injection of glyoxylate (GOX) for 6 days. For the ß3-stimulant experiment, mice were administered intra-abdominal injections of the ß3-stimulant (ß3-group) or saline (control group) for 6 days. Thereafter, renal crystal deposition was induced by intra-abdominal injection of GOX for 6 days. iBAT removal decreased the expression of Sod1 and increased that of chemokine (C-C motif) ligand 2 (Ccl2), EGF module-containing mucin-like receptor 1 (Emr1), and tumor necrosis factor (Tnf) in the kidneys. Renal crystal deposition was 2.06-fold higher in the X-BAT group than in the sham group. The ß3-stimulant caused differentiation of white adipocytes into brown-like adipocytes. In the kidneys of the ß3-group, the expression of Ccl2 and Emr1 decreased and that of Sod1 increased. Renal crystal deposition was 0.17-fold lower in the ß3-group than in the control group. In summary, iBAT removal promoted kidney inflammation and renal crystal formation. ß3-Stimulant-induced brown-like adipocytes reduced inflammation and improved antioxidant action in the kidneys, which suppressed renal crystal formation. This is the first report on the therapeutic role of brown and brown-like adipocytes for kidney stone formation.

Reduced adiposity by compensatory WAT browning upon iBAT removal in mice.

The strong effects of classic brown adipose tissue (BAT) and recruited beige adipocytes in treatment of obesity and metabolic syndrome have been attracting increasing research interest. Cold treatment is an effective, convenient approach to stimulate BAT activity and induce white adipose tissue (WAT) browning. Here, we utilized prolonged cold exposure (from 2 h to 2 weeks in a 4° cold chamber) to elucidate dynamic changes in BAT and in WAT browning during acute and chronic cold exposure in mice. BAT mass decreased quickly, with reduced lipid droplet sizes within 8 h of cold exposure owing to the utilization of BAT pre-storage triglycerides, and subsequently increased during prolonged cold exposure. These dynamic morphological changes in BAT were confirmed by gene expression changes in ADRB3 and PGC1α, while UCP1 and ELOVL3 expression was continuously up-regulated throughout the entire cold exposure period. Additionally, cold treatment increased BAT secretion of FGF21, which has been reported to activate beige adipocyte formation. Thus, to illustrate potential crosstalk between secreted BAT proteins (so-called BATokines) and beige adipogenesis during cold stress, we performed an interscapular BAT (iBAT) removal experiment in mice. Surprisingly, loss of classic iBAT enhanced WAT browning due to compensatorily increased sympathetic WAT input. Unexpectedly, we observed significantly reduced adiposity in the iBAT removal group compared with the control group. These results further suggest that WAT browning plays an important role in whole-body energy metabolism during cold acclimation, even without iBAT. Furthermore, our data imply that enhanced WAT browning may be an efficient therapeutic tool to combat obesity and related syndromes.

Removal of interscapular brown adipose tissue increases aortic stiffness despite normal systemic glucose metabolism in mice.

Brown adipose tissue (BAT) is considered protective against obesity and related cardiometabolic dysfunction. Indeed, activation of BAT improves glucose homeostasis and attenuates cardiovascular disease development. However, whether a reduction in BAT mass perturbs metabolic function and increases risk for cardiovascular disease remains largely unknown. To address this question, C57BL/6J male mice underwent a sham procedure or surgical bilateral excision of interscapular BAT (iBATx) and were fed a normal chow or a Western diet for 18 wk, creating four groups ( n = 10/group). Mice were housed at 25°C. As expected, the Western diet increased final body weight and adiposity; however, contrary to our hypothesis, iBATx did not potentiate adiposity independent of diet. Furthermore, iBATx did not affect indexes of glycemic control (HbA1c, fasting glucose and insulin, and glucose area under the curve during a glucose tolerance test) and produced minimal-to-no effects on lipid homeostasis. The absence of metabolic disturbances with iBATx was not attributed to regrowth of iBAT or a "browning" or proliferative compensatory response of other BAT depots. Notably, iBATx caused an increase in aortic stiffness in normal chow-fed mice only, which was associated with an increase in aortic uncoupling protein-1. Collectively, we demonstrated that, at 25°C (i.e., limited thermal stress conditions), a substantial reduction in BAT mass via iBATx does not disrupt systemic glucose metabolism, challenging the current dogma that preservation of BAT is obligatory for optimal metabolic function. However, iBATx caused aortic stiffening in lean mice, hence supporting the existence of an interplay between iBAT and aortic stiffness, independent of alterations in glucose homeostasis.

Age-Dependent Control of Energy Homeostasis by Brown Adipose Tissue in Progeny Subjected to Maternal Diet-Induced Fetal Programming.

Epidemiological and animal studies show that deleterious maternal environments predispose aging offspring to metabolic disorders and type 2 diabetes. Young progenies in a rat model of maternal low-protein (LP) diet are normoglycemic despite collapsed insulin secretion. However, without further worsening of the insulin secretion defect, glucose homeostasis deteriorates in aging LP descendants. Here we report that normoglycemic and insulinopenic 3-month-old LP progeny shows increased body temperature and energy dissipation in association with enhanced brown adipose tissue (BAT) activity. In addition, it is protected against a cold challenge and high-fat diet (HFD)-induced obesity with associated insulin resistance and hyperglycemia. Surgical BAT ablation in 3-month-old LP offspring normalizes body temperature and causes postprandial hyperglycemia. At 10 months, BAT activity declines in LP progeny with the appearance of reduced protection to HFD-induced obesity; at 18 months, LP progeny displays a BAT activity comparable to control offspring and insulin resistance and hyperglycemia occur. Together our findings identify BAT as a decisive physiological determinant of the onset of metabolic dysregulation in offspring predisposed to altered ß-cell function and hyperglycemia and place it as a critical regulator of fetal programming of adult metabolic disease.

Intraosseous hibernoma: a case report and review of the literature.

STUDY DESIGN: A case report and a literature review are presented. OBJECTIVE: To describe and review the clinical presentation and characteristic imaging and pathology findings of intraosseous hibernoma. SUMMARY OF BACKGROUND DATA: Hibernomas are lesions of brown fat. Brown fat is typically found in newborn mammals and is rich in mitochondria, thus enabling its role in thermoregulation. It represents a small proportion of adult fat and is distinct from the more common "white fat." Rarely does a hibernoma occur within bone. To the authors' knowledge, 5 cases in all have been reported in the literature. METHODS: We report the first case to our knowledge of an intraosseous hibernoma occurring within the lumbar spine as well as a review of the literature. RESULTS: Characteristic findings from magnetic resonance studies include variable T1W signal relative to skeletal muscle and hyperintense signal on fluid-sensitive imaging. Computed tomography has consistently demonstrated a sclerotic lesion with variable definition. Pathologic findings include sheets of multivacuolated cells with centrally placed nuclei and numerous tiny surrounding cytoplasmic vacuoles overlying bony trabeculae. CONCLUSION: Our review of the literature demonstrates that intraosseous hibernoma is most likely an incidental finding with a predilection for the lower extremities in middle-aged females. LEVEL OF EVIDENCE: 4.

Localization, identification, and excision of murine adipose depots.

Obesity has increased dramatically in the last few decades and affects over one third of the adult US population. The economic effect of obesity in 2005 reached a staggering sum of $190.2 billion in direct medical costs alone. Obesity is a major risk factor for a wide host of diseases. Historically, little was known regarding adipose and its major and essential functions in the body. Brown and white adipose are the two main types of adipose but current literature has identified a new type of fat called brite or beige adipose. Research has shown that adipose depots have specific metabolic profiles and certain depots allow for a propensity for obesity and other related disorders. The goal of this protocol is to provide researchers the capacity to identify and excise adipose depots that will allow for the analysis of different factorial effects on adipose; as well as the beneficial or detrimental role adipose plays in disease and overall health. Isolation and excision of adipose depots allows investigators to look at gross morphological changes as well as histological changes. The adipose isolated can also be used for molecular studies to evaluate transcriptional and translational change or for in vitro experimentation to discover targets of interest and mechanisms of action. This technique is superior to other published techniques due to the design allowing for isolation of multiple depots with simplicity and minimal contamination.

Analysis and measurement of the sympathetic and sensory innervation of white and brown adipose tissue.

Here, we provide a detailed account of how to denervate white and brown adipose tissue (WAT and BAT) and how to measure sympathetic nervous system (SNS) activity to these and other tissues neurochemically. The brain controls many of the functions of WAT and BAT via the SNS innervation of the tissues, especially lipolysis and thermogenesis, respectively. There is no clearly demonstrated parasympathetic innervation of WAT or the major interscapular BAT (IBAT) depot. WAT and BAT communicate with the brain neurally via sensory nerves. We detail the surgical denervation (eliminating both innervations) of several WAT pads and IBAT. We also detail more selective chemical denervation of the SNS innervation via intra-WAT/IBAT 6-hydroxy-dopamine (a catecholaminergic neurotoxin) injections and selective chemical sensory denervation via intra-WAT/IBAT capsaicin (a sensory nerve neurotoxin) injections. Verifications of the denervations are provided (HPLC-EC detection for SNS, ELIA for calcitonin gene-related peptide (proven sensory nerve marker)). Finally, assessment of the SNS drive to WAT/BAT or other tissues is described using the alpha-methyl-para-tyrosine method combined with HPLC-EC, a direct neurochemical measure of SNS activity. These methods have proven useful for us and for other investigators interested in innervation of adipose tissues. The chemical denervation approach has been extended to nonadipose tissues as well.

Cellular mechanisms by which FGF21 improves insulin sensitivity in male mice.

Fibroblast growth factor 21 (FGF21) is a potent regulator of glucose and lipid metabolism and is currently being pursued as a therapeutic agent for insulin resistance and type 2 diabetes. However, the cellular mechanisms by which FGF21 modifies insulin action in vivo are unclear. To address this question, we assessed insulin action in regular chow- and high-fat diet (HFD)-fed wild-type mice chronically infused with FGF21 or vehicle. Here, we show that FGF21 administration results in improvements in both hepatic and peripheral insulin sensitivity in both regular chow- and HFD-fed mice. This improvement in insulin responsiveness in FGF21-treated HFD-fed mice was associated with decreased hepatocellular and myocellular diacylglycerol content and reduced protein kinase Cε activation in liver and protein kinase Cθ in skeletal muscle. In contrast, there were no effects of FGF21 on liver or muscle ceramide content. These effects may be attributed, in part, to increased energy expenditure in the liver and white adipose tissue. Taken together, these data provide a mechanism by which FGF21 protects mice from lipid-induced liver and muscle insulin resistance and support its development as a novel therapy for the treatment of nonalcoholic fatty liver disease, insulin resistance, and type 2 diabetes.

Hibernoma--a case series with multimodality imaging and pathologic correlation.

Hibernoma is an uncommon, benign tumor of brown fat origin. The distribution of this tumor originally was described as following the location of persistent brown fat within the subcutaneous tissue of the thorax (especially the periscapular and interscapular regions), neck, axilla, shoulder, and retroperitoneum. Recently, hibernoma was described as being most common in the thigh.

Partial removal of brown adipose tissue enhances humoral immunity in warm-acclimated Mongolian gerbils (Meriones unguiculatus).

Temperate rodent species experience marked seasonal fluctuations in environmental temperatures. High thermoregulatory demands during winter usually weaken immune function. Brown adipose tissue (BAT) plays a crucial role in adaptive thermoregulatory process. Thus, we proposed the hypothesis that BAT might participate in the regulation of seasonal changes in immune function. The present study examined the trade-off between thermoregulation and immune function and the potential role of BAT in regulating seasonal changes in immune function in Mongolian gerbils. Specifically, surgical removal of interscapular BAT (34% of total BAT) was performed in male gerbils, and subsequently acclimated to either warm (23 ± 1 °C) or cold (4 ± 1 °C) conditions. Gerbils were then challenged with innocuous antigens and the immune responses were measured. Resting metabolic rate (RMR) and nonshivering thermogenesis (NST) were increased under cold conditions. However, the cost of thermoregulation during cold acclimation did not suppress T-cell mediated immunity and humoral immunity or decrease spleen mass, thymus mass and white blood cells. Partial removal of BAT significantly enhanced humoral immunity in warm-acclimated, but not in cold-acclimated gerbils. T-cell mediated immunity, white blood cells and immune organs were not affected by BAT removal under both warm and cold conditions. Collectively, our results imply that BAT has a suppressive effect on humoral immunity in warm-acclimated gerbils and differential effects of BAT on humoral immunity under different temperatures (e.g., summer and winter) might be benefit to their survival.

Cannabinoid receptor 1 (CB1) antagonism enhances glucose utilisation and activates brown adipose tissue in diet-induced obese mice.

AIMS/HYPOTHESIS: We examined the physiological mechanisms by which cannabinoid receptor 1 (CB1) antagonism improves glucose metabolism and insulin sensitivity independent of its anorectic and weight-reducing effects, as well as the effects of CB1 antagonism on brown adipose tissue (BAT) function. METHODS: Three groups of diet-induced obese mice received for 1 month: vehicle; the selective CB1 antagonist SR141716; or vehicle/pair-feeding. After measurements of body composition and energy expenditure, mice underwent euglycaemic-hyperinsulinaemic clamp studies to assess in vivo insulin action. In separate cohorts, we assessed insulin action in weight-reduced mice with diet-induced obesity (DIO), and the effect of CB1 antagonism on BAT thermogenesis. Surgical denervation of interscapular BAT (iBAT) was carried out in order to study the requirement for the sympathetic nervous system in mediating the effects of CB1 antagonism on BAT function. RESULTS: Weight loss associated with chronic CB1 antagonism was accompanied by increased energy expenditure, enhanced insulin-stimulated glucose utilisation, and marked activation of BAT thermogenesis. Insulin-dependent glucose uptake was significantly increased in white adipose tissue and BAT, whereas glycogen synthesis was increased in liver, fat and muscle. Despite marked weight loss in the mice, SR141716 treatment did not improve insulin-mediated suppression of hepatic glucose production nor increase skeletal muscle glucose uptake. Denervation of iBAT blunted the effect of SR141716 on iBAT differentiation and insulin-mediated glucose uptake. CONCLUSIONS/INTERPRETATION: Chronic CB1 antagonism markedly enhances insulin-mediated glucose utilisation in DIO mice, independent of its anorectic and weight-reducing effects. The potent effect on insulin-stimulated BAT glucose uptake reveals a novel role for CB1 receptors as regulators of glucose metabolism.

White adipose tissue re-growth after partial lipectomy in high fat diet induced obese wistar rats.

The effects of partial removal of epididymal (EPI) and retroperitoneal (RET) adipose tissues (partial lipectomy) on the triacylglycerol deposition of high fat diet induced obese rats were analyzed, aiming to challenge the hypothesized body fat regulatory system. Male 28-day-old wistar rats received a diet enriched with peanuts, milk chocolate and sweet biscuits during the experimental period. At the 90th day of life, rats were submitted to either lipectomy (L) or sham surgery. After 7 or 30 days, RET, EPI, liver, brown adipose tissue (BAT), blood and carcass were obtained and analyzed. Seven days following surgery, liver lipogenesis rate and EPI relative weight were increased in L. After 30 days, L, RET and EPI presented increased lipogenesis, lipolysis and percentage of small area adipocytes. L rats also presented increased liver malic enzyme activity, BAT lipogenesis, and triacylglycerol and corticosterone serum levels. The partial removal of visceral fat pads affected the metabolism of high fat diet obese rats, which leads to excised tissue re-growth and possibly compensatory growth of non-excised depots at a later time.

[Diffuse uptake of brown fat on computed-tomography coupled positron emission tomoscintigraphy (PET-CT) for the exploration of extra-adrenal pheochromocytoma]. / Hyperfixation diffuse de la graisse brune à la tomoscintigraphie par émission de positons couplée à la tomodensitométrie (TEP-TDM) dans l'exploration d'un phéochromocytome extra surrénalien.

We report an observation of strong bilateral uptake on a PET-CT scan compatible with activation of brown adipose tissue in a patient with extra-adrenal pheochromocytoma. A 42-year-old man was hospitalized for hypersudation together with weight loss and palpitations. Heart rate was 120 bpm and fasting blood glucose 1.36 g/l. Endocrine explorations revealed elevated serum chromogranine which reached 517 ng/ml (19-38). The norepinephrine level reached 49.7 nmol/l (<4.00) and urinary norepinephrine and normetanephrine levels reached 13977 nmol/24h (<414) and 32 micromol/24h (0.4-2.5) respectively. The thoraco-abdominal and pelvic scan showed a 6 cm diameter paraaortic hypervascularized mass with an infiltrative lesion of both perirenal area and mediastinal tissue without adenopathies. The abdominal MRI revealed the mass with a low intensity signal in T1 and a slight high intensity signal in T2. MIBG and octreoscan scintigraphies were negative. 18F-DG PET showed intensed uptake in the tumor mass together with intense, diffuse and bilateral uptake above and below the diaphragm. The mass was resected. Histological examination of the surgical specimen confirmed the diagnosis of extra-adrenal pheochromocytoma with an index of 13% cellular proliferation without cell atypia. There was a hypervascularization with small islets of brown adipose tissue in the perirenal fat. Both plasmatic and urinary catecholamines decreased to the normal range after the operation and PET-scan normalized. Bilateral spread of the radiotracer uptake was probably due to brown adipose tissue activation by excessive sympathetic stimulation induced by catecholamines released by the tumor.

Hibernoma arising from the adrenal gland.

Hibernomas, or "brown fat" tumors, arising from the adrenal gland, have not been reported previously. These benign lesions consist of brown fat and demonstrate inert features. The most common anatomic location of these tumors is in the adipose tissue of the thigh, shoulder, chest, and back. We describe a hibernoma within the adrenal gland in close association with a myelolipoma that was excised for its solid enlarging characteristics.