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Pentraxin 3 (PTX3) is a soluble pattern recognition receptor playing an important role in immune response and inflammation. Lipopolysaccharide (LPS) stimulation can significantly induce PTX3 expression and secretion in adipocytes. Appropriate regulation of PTX3 secretion is critical for inflammatory homeostasis. Using chemical inhibitors of conventional and unconventional protein secretion, we explored the mechanisms that control LPS-stimulated PTX3 secretion in 3T3-L1 adipocytes. Inhibiting the conventional protein secretion blocked LPS-stimulated PTX3 secretion, resulting in cellular PTX3 accumulation in adipocytes. We also detected PTX3 in exosomes from LPS-treated adipocytes; inhibiting exosome trafficking attenuated PTX3 secretion. However, only 4.3% of secreted PTX3 was detected in exosomes compared to 95.7% in the non-exosomal fractions. The fractionation of isolated exosomes by the iodixanol density gradient centrifugation confirmed that a small portion of secreted PTX3 overlapped with exosomal markers in small extracellular-vesicle fractions. We conclude that PTX3 is secreted mainly through conventional protein secretion, and a small percentage of PTX3 is released in exosomes from LPS-stimulated adipocytes.

Introduction: Erythema nodosum (EN) is the most common type of panniculitis. The most frequent etiological factors are streptococcal pharyngitis, sarcoidosis, Behçet's disease, and tuberculosis. Our objective was to identify the etiological factors and to evaluate the patients' clinical, laboratory, and histopathological findings., Methods: Eighty-eight patients diagnosed with EN at our clinic between 2013 and 2019 were evaluated retrospectively. Sixty-five patients were evaluated histopathologically., Results: The patients' ages ranged between 17 and 76 (mean age: 41.91 ± 13.07 years). EN was 7.8 times more frequent in women. Patients presenting with idiopathic EN were significantly older than secondary cases (p < 0.05). Sixty-one patients (69.3%) had an underlying disease (secondary EN). The most common etiological factors were upper respiratory tract infections (n = 26), followed by Behçet's disease (n = 20). Septal panniculitis was present in 89.2% of cases evaluated histopathologically. Mixed or lobular panniculitis was present in 35.7% of Behçet's disease patients with EN-like lesions. Vasculitis was also noted in 35.7% of Behçet's disease patients., Conclusions: Our data confirm the predominance of upper respiratory tract infections and Behçet's disease among patients with EN in Turkey. Behçet's disease patients presenting with EN-like lesions may show mixed panniculitis and vasculitis, whereas classic EN patients predominantly show septal panniculitis.

Pancreatic panniculitis (PP) is a rare clinical variant of subcutaneous fat necrosis, developing in patients with a variety of pancreatic diseases such as acute or chronic pancreatitis, tumors and cysts. The tumor-associated PP represents a noteworthy skin manifestation of underlying internal malignancies, also known as dermadrome. Among causative pancreatic tumors, acinar cell carcinoma is the most frequent malignancy; however, little is known about how the origin of tumor cells and progression stage of pancreatic tumors potentially contribute to the establishment of panniculitis. Here, we present a 69-year-old Japanese male case of clinically aggressive PP on the bilateral legs, whose skin lesions developed prior to the diagnosis of occult pancreatic tumor and liver metastasis. Moreover, the immunopathology of the pancreatic lesion revealed neuroendocrine tumor (NET), a rare pathological variant. Skin lesions immediately spread to the upper limbs with extensive ulcerations and necrosis, accompanied by high levels of serum lipase and elastase, but not with other pancreatic enzymes. He died 2 months after the initial development of the skin lesion due to rapid deterioration of general condition. We reviewed 14 cases, including ours, of PP with NET in the pancreas thus far reported, to identify the clinicopathological characteristics regarding to what extent this rare complication could reflect the clinical course of pancreatic tumors and overall prognosis. Our published work review found that the disease has a significant male predominance (male : female, 13:1) and cases with occult pancreatic tumors died within 4 months after the development of their skin lesions. Our case was the poorest prognostic outcome. This report emphasizes that dermatologists should recognize PP with NET, reflecting a fatal prognosis, and to make a prompt diagnosis., (© 2020 Japanese Dermatological Association.)

Scope: Punicalagin (PU)-rich pomegranate peel extract has been shown before to exert protective effects against high fat-induced hepatic damage. The aim of this study is to explore whether and how PU antagonizes hepatic steatosis in Western diet-fed (WD) mice., Methods and Results: Mice are fed either chow diet, WD (containing 42% fat, 15% protein, and 43% carbohydrates), or WD supplemented with PU (50 mg kg -1 body weight/day) for 13 weeks. Weight gain, hepatic fat content, and inflammation in the liver and adipose tissues are measured. Compared to the WD group, PU-treated mice have lower fat content, decreased levels of alanine transaminase, and inflammation in liver. PU also changed the transcriptional expression of important genes in fatty acid oxidation pathway and alleviated glucose intolerance. Furthermore, PU improved adiponectin signaling and lipid metabolism in visceral adipose tissue. Moreover, PU improved gut microbiota dysbiosis induced by WD and enhanced gut barrier function., Conclusions: The findings suggest that PU improves hepatic steatosis induced by WD, in part through regulating lipid homeostasis and inflammation in liver and adipose tissue and restoring microbiota shift and impaired gut barrier function. Thus, PU can be potentially developed as a potential prevention strategy in combating nonalcoholic fatty liver disease., (© 2021 Wiley-VCH GmbH.)

Pancreatic panniculitis is a rare complication of pancreatic diseases. We aimed to evaluate a case of pancreatic panniculitis. A 58-year-old woman was referred to our hospital with complaints of painful cutaneous nodules on her limbs. Various diagnostic tests confirmed pancreatic panniculitis and pancreatic adenosquamous carcinoma. We diagnosed pancreatic panniculitis by a skin nodule biopsy that revealed fine basophilic material within anucleate cells and neutrophil infiltration. Abdominal imaging detected a tumor with necrosis on the pancreas and endoscopic ultrasound-guided fine-needle aspiration revealed it as an adenocarcinoma. The patient underwent pancreatoduodenectomy after neoadjuvant chemotherapy. The tumor was composed of differentiated adenocarcinoma and squamous cell carcinoma and diagnosed as adenosquamous carcinoma. This is the first report of pancreatic panniculitis in a patient with adenosquamous cell carcinoma of the pancreas.

Accumulating evidence reveals that adipose tissue is an immunologically active organ that exerts multiple impacts on the regulation of systemic energy metabolism. Adipose tissue immunity is modulated by the interactions between adipocytes and various immune cells. Nevertheless, the underlying mechanisms that control inter-cellular interactions between adipocytes and immune cells in adipose tissue have not been thoroughly elucidated. Recently, it has been demonstrated that adipocytes utilize lipid metabolites as a key mediator to initiate and mediate diverse adipose tissue immune responses. Adipocytes present lipid antigens and secrete lipid metabolites to determine adipose immune tones. In addition, the interactions between adipocytes and adipose immune cells are engaged in the control of adipocyte fate and functions upon metabolic stimuli. In this review, we discuss an integrated view of how adipocytes communicate with adipose immune cells using lipid metabolites. Also, we briefly discuss the newly discovered roles of adipose stem cells in the regulation of adipose tissue immunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Park, Sohn, Han, Park, Huh, Choe and Kim.)

High-fat diet (HFD)-induced inflammation and steatosis of adipose tissue and liver are associated with a variety of serious health risks. Sialic acids are found as the distal terminal sugar on glycoproteins, which are removed by sialidases (neuraminidases). In humans and mice, pulmonary fibrosis is associated with up-regulation of sialidases, and injections of sialidase inhibitors attenuate bleomycin-induced pulmonary fibrosis. Sialidase levels are altered in obese rodents and humans. This report shows that for mice on an HFD, injections of the sialidase inhibitor N-acetyl-2,3-dehydro-2-deoxyneuraminic acid inhibit weight gain, reduce steatosis, and decrease adipose tissue and liver inflammation. Compared with control, mice lacking the sialidase neuraminidase 3 have reduced HFD-induced adipose tissue and liver inflammation. These data suggest that sialidases promote adipose and liver inflammation in response to a high-fat diet., (Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Scope: Glucose intolerance during pregnancy is associated with short- and long-term maternal and offspring health consequences. In young male mice, knockout of the major pro-inflammatory mediator interleukin-1-receptor-1 (IL1R1) protects against high-fat diet (HFD)-induced glucose intolerance and metabolic dysfunction. This phenotype has not been examined during pregnancy. The hypothesis that IL1R1 depletion will protect females against HFD-induced glucose intolerance and metabolic dysfunction before, during, and post pregnancy is tested., Methods and Results: C57BL/6J control and IL1R1 knockout (IL1R1 -/- ) mice are randomized to either a control diet (10% kcal from fat) or HFD (45% kcal from fat), and three distinct cohorts are established: nulliparous, pregnant, and postpartum females. Contrary to the authors' hypothesis, it is found that IL1R1 -/- does not protect against glucose intolerance in nulliparous or pregnant females, and while control HFD animals see a resolution of glucose tolerance postpartum, IL-1R1 -/- mice remain impaired. These effects are accompanied by adipocyte hypertrophy, hyperleptinemia, and increased adipose tissue inflammatory gene expression. Maternal genotype differentially affects fetal growth in male and female fetuses, demonstrating sexual dimorphism in this genotype prior to birth., Conclusions: These findings suggest that IL1R1 signaling is important for normal metabolic functioning in females, during and outside of pregnancy., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: Smooth muscle cells and pericytes display remarkable plasticity during injury and disease progression. Here, we tested the hypothesis that perivascular cells give rise to Klf4 -dependent macrophage-like cells that augment adipose tissue (AT) inflammation and metabolic dysfunction associated with diet-induced obesity (DIO). Approach and Results: Using Myh11-Cre ERT2 eYFP (enhanced yellow fluorescent protein) mice and flow cytometry of the stromovascular fraction of epididymal AT, we observed a large fraction of smooth muscle cells and pericytes lineage traced eYFP + cells expressing macrophage markers. Subsequent single-cell RNA sequencing, however, showed that the majority of these cells had no detectable eYFP transcript. Further exploration revealed that intraperitoneal injection of tamoxifen in peanut oil, used for generating conditional knockout or reporter mice in thousands of previous studies, resulted in large increase in the autofluorescence and false identification of macrophages within epididymal AT as being eYFP + ; and unintended proinflammatory consequences. Using newly generated Myh11-Dre ERT2 tdTomato mice given oral tamoxifen, we virtually eliminated the problem with autofluorescence and identified 8 perivascular cell dominated clusters, half of which were altered upon DIO. Given that perivascular cell KLF4 (kruppel-like factor 4) can have beneficial or detrimental effects, we tested its role in obesity-associated AT inflammation. While smooth muscle cells and pericytes-specific Klf4 knockout (smooth muscle cells and pericytes Klf4 Δ/Δ ) mice were not protected from DIO, they displayed improved glucose tolerance upon DIO, and showed marked decreases in proinflammatory macrophages and increases in LYVE1 + lymphatic endothelial cells in the epididymal AT., Conclusions: Perivascular cells within the AT microvasculature dynamically respond to DIO and modulate tissue inflammation and metabolism in a KLF4-dependent manner.

Adipocyte-mediated inflammatory signalling has been proposed to alter adipose physiology in obesity and Type 2 diabetes mellitus. Novel targets for alteration of inflammatory signalling are needed to improve obesity-related outcomes. The γ-secretase enzyme complex has been suggested to play a role both in adipocyte function as well as in immune regulation. We hypothesized that adipocyte-specific γ-secretase inhibition could alter the inflammatory makeup of adipose tissue. We found that genetic blockade of γ-secretase in adipocytes leads to a decrease in EMR1 (F4/80) expression, as a marker of macrophage presence, in adipose tissue without changes in expression of markers of other inflammatory cell types. To explore the mechanism by which adipocytes can alter macrophage function in vitro , fully differentiated 3T3-L1 adipocytes were treated with a γ-secretase inhibitor in the presence of lipopolysaccharide (LPS) and transcription of IL6 and ccl2 (MCP1) were quantified. IL-6 expression and secretion were significantly inhibited by γ-secretase blockade, with little effect on MCP1. Preconditioned media from 3T3-L1 adipocytes treated with a γ-secretase inhibitor also alters macrophage activation but did not affect macrophage translocation in vitro . Therefore, γ-secretase inhibition in fully differentiated adipocytes can alter IL-6 signalling to macrophages, consistent with our hypothesis that that γ-secretase is involved in adipocyte-initiated inflammatory signalling cascades.

A 5-year-old male neutered domestic shorthair cat suffered from recurrent solitary nodules in different subcutaneous body regions. Nodules were surgically removed and each time histopathological diagnosis was fat necrosis and fibrosing to pyogranulomatous panniculitis. After the second surgery the alpha (α)-tocopherol concentration in serum of the cat was examined and the result (21 mg/L) exceeded the upper limit of the reference interval (3-11 mg/L). Vitamin E amount in diet fed solely in the past was checked as studies have shown that vitamin E amounts in food significantly influence vitamin E concentrations in serum. For comparative purposes, α-tocopherol concentrations were determined in sera of healthy control cats. Additionally, vitamin E amount in wet food from different manufacturers was analysed using gas chromatography coupled to mass spectrometry (GC-MS). The results showed that the diet did not have higher vitamin E amounts compared to other diets. All control cats had similar high serum α-tocopherol concentrations. We conclude that panniculitis can occur despite high serum α-tocopherol concentrations in cats. Further studies are needed to redefine reference values of α-tocopherol in serum of cats., (© 2020 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

Neutrophilic infiltrates in panniculitis can be seen in different clinical-pathological entities. There are a "mostly neutrophilic inflammatory infiltrate" in some entities classically defined as neutrophilic panniculitis and already included in algorithms, such as enzymatic panniculitis, infective and factitial ones, erythema induratum, or subcutaneous Sweet syndrome, but there are also other panniculitis where neutrophils are frequently observed such as panniculitis associated with inflammatory bowel disease or rheumatoid arthritis, or drug-induced panniculitis associated with BRAF inhibitors, and finally, some panniculitis are better classified in other panniculitides groups but may present with neutrophil-rich variants, such as the neutrophil-rich subcutaneous fat necrosis of the newborn. We review the main clinical and histopathological features of most of these panniculitides and construct a diagnostic algorithm including these diseases.

Skin findings are common among patients with hematological malignancies and are thought to be expressions of a reactive spectrum peculiar to immunosuppressed patients with an unclear pathogenesis. Eosinophilic panniculitis is a reaction pattern defined by single or multiple lesions consisting in nodules and plaques, and sometimes in papules and pustules, characteristically associated to hematological neoplasms or to a series of benign conditions such as arthropod bites. We report a case of eosinophilic panniculitis occurring in a 77-year-old woman with chronic lymphocytic leukemia. Our case is remarkable as the histology of panniculitis was associated with a clinical evidence of dermal papules and a history of insect bites.

Objective: Glucose-dependent insulinotropic polypeptide (GIP) conveys information from ingested nutrients to peripheral tissues, signaling energy availability. The GIP Receptor (GIPR) is also expressed in the bone marrow, notably in cells of the myeloid lineage. However, the importance of gain and loss of GIPR signaling for diverse hematopoietic responses remains unclear., Methods: We assessed the expression of the Gipr in bone marrow (BM) lineages and examined functional roles for the GIPR in control of hematopoiesis. Bone marrow responses were studied in (i) mice fed regular or energy-rich diets, (ii) mice treated with hematopoietic stressors including acute 5-fluorouracil (5-FU), pamsaccharide (LPS), and Pam3CysSerLys4 (Pam3CSK4), with or without pharmacological administration of a GIPR agonist, and (iii) mice with global (Gipr -/- ) or selective deletion of the GIPR (Gipr Tie2-/- ) with and without bone marrow transplantation (BMT)., Results: Gipr is expressed within T cells, myeloid cells, and myeloid precursors; however, these cell populations were not different in peripheral blood, spleen, or BM of Gipr -/- and Gipr Tie2-/- mice. Nevertheless, gain and loss of function studies revealed that GIPR signaling controls the expression of BM Toll-like receptor (TLR) and Notch-related genes regulating hematopoiesis. Loss of the BM GIPR attenuates the extent of adipose tissue inflammation and dysregulates the hematopoietic response to BMT. GIPR agonism modified BM gene expression profiles following 5-FU and Pam3CSK4 whereas loss of the Gipr altered the hematopoietic responses to energy excess, two TLR ligands, and 5-FU. However, the magnitude of the cellular changes in hematopoiesis in response to gain or loss of GIPR signaling was relatively modest., Conclusion: These studies identify a functional gut hormone-BM axis positioned for the transduction of signals linking nutrient availability to the control of TLR and Notch genes regulating hematopoiesis. Nevertheless, stimulation or loss of GIPR signaling has minimal impact on basal hematopoiesis or the physiological response to hematopoietic stress., (Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Objective: Expansion of visceral adipose tissue (VAT) and metabolic inflammation are consequences of obesity and associated with type 2 diabetes (T2DM). Metabolically activated adipose tissue macrophages (ATMs) undergo qualitative and quantitative changes that influence their inflammatory responses. How these cells contribute to insulin resistance (IR) in humans is not well understood. Cholesterol 25-Hydroxylase (CH25H) converts cholesterol into 25-Hydroxycholesterol (25-HC), an oxysterol that modulates immune responses. Using human and murine models, we investigated the role of CH25H in metabolic inflammation., Methods: We performed transcriptomic (RNASeq) analysis on the human whole AT biopsies and sorted ATMs from obese non-diabetic (NDM) and obese diabetic (DM) subjects to inquire if CH25H was increased in DM. We challenged mice lacking Ch25h with a high-fat diet (HFD) to characterize their metabolic and immunologic profiling. Ch25h KO mice and human adipose tissue biopsies from NDM and DM subjects were analyzed. LC-MS was conducted to measure 25-HC level in AT. In vitro analysis permitted us to investigate the effect of 25-HC on cytokine expression., Results: In our RNASeq analysis of human visceral and subcutaneous biopsies, gene pathways related to inflammation were increased in obese DM vs. non-DM subjects that included CH25H. CH25H was enriched in the stromal vascular fraction of human adipose tissue and highly expressed in CD206 + human ATMs by flow cytometry analysis. We measured the levels of the oxysterols, 25-HC and 7α25diHC, in human visceral adipose tissue samples and showed a correlation between BMI and 25-HC. Using mouse models of diet-induced obesity (DIO), we found that HFD-induced Ch25h expression in eWAT and increased levels of 25-HC in AT. On HFD, Ch25h KO mice became obese but exhibited reduced plasma insulin levels, improved insulin action, and decreased ectopic lipid deposit. Improved insulin sensitivity in Ch25h KO mice was due to attenuation of CD11c + adipose tissue macrophage infiltration in eWAT. Finally, by testing AT explants, bone marrow-derived macrophages (BMDMs) and SVF cells from Ch25h deficient mice, we observed that 25-HC is required for the expression of pro-inflammatory genes. 25-HC was also able to induce inflammatory genes in preadipocytes., Conclusions: Our data suggest a critical role for CH25H/25-HC in the progression of meta-inflammation and insulin resistance in obese humans and mouse models of obesity. In response to obesogenic stimuli, CH25H/25-HC could exert a pro-inflammatory role., (Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Pancreatic panniculitis is a rare skin manifestation in pancreatic disease patients that most frequently develops on the lower legs. We report the unique case of a 68-year-old man who suffered from pancreatic panniculitis on his trunk associated with acute pancreatitis due to an intraductal papillary mucinous neoplasm., Case Presentation: A 68-year-old man complained of a 2-day history of a tender subcutaneous nodule on his trunk. Laboratory tests and abdominal contrast computed tomography were consistent with acute pancreatitis due to an intraductal papillary mucinous neoplasm. A skin biopsy of the nodule histologically displayed lobular panniculitis with characteristic "ghost cells", which indicated pancreatic panniculitis., Conclusions: In order to avoid a missed or delayed diagnosis, clinicians should bear in mind that pancreatic panniculitis can be the first manifestation of pancreatic disease when encountering subcutaneous nodules on the trunk.

Scope: The authors aim to investigate the mechanisms by which red raspberry (RR) polyphenolic fractions regulate obesity and inflammation with an emphasis on the crosstalk between adipose tissue macrophages (ATM) and adipocyte progenitors., Methods and Results: C57BL/6 male mice are fed either a high-fat (HF) diet or an HF diet supplemented with a RR polyphenolic fraction from whole fruit, pulp, or seed. Supplementation with pulp significantly increases energy expenditure and reduces HF-diet-induced obesity and insulin resistance. The pulp, and to a lesser extent, whole polyphenols, decreases the recruitment of ATM, activation of the nod-like receptor protein 3 (NLRP3) inflammasome, and adipocyte hypertrophy, which is associated with epigenetic modulation of adipogenesis (e.g., H3K27Ac, H3K9Ac). Results from an IL-1β reporter assay in J774 macrophages recapitulate the inhibitory role of RR polyphenols on NLRP3 inflammasome activation. Using conditioned media from macrophages, it is demonstrated that RR polyphenols reverse the IL-1β-mediated epigenetic suppression of H3K27Ac in adipocyte progenitor cells., Conclusions: RR polyphenols from pulp and whole fruit serve as an inhibitor for NLRP3 inflammasome activation and an epigenetic modifier to regulate adipogenesis, which confers resistance against diet-induced obesity and metabolic dysfunction., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: The alpha7 nicotinic acetylcholine receptor (α7nAChR), involved in the modulation of inflammation and insulin sensitivity, is downregulated in white adipose tissue (WAT) of obese patients. This study aims to test the ability of a selective synthetic α7nAChR agonist, the spirocyclic Δ 2 -isoxazoline derivative (R)-(-)-ICH3 (ICH3), to counteract acute inflammation and obesity-associated modifications in WAT., Methods: We employed the LPS-septic shock murine model, human primary adipocytes and diet-induced obese (DIO) mice. Inflammatory factor expression was assessed by ELISA and quantitative real-time PCR. Flow cytometry was employed to define WAT inflammatory infiltrate. Insulin signaling was monitored by quantification of AKT phosphorylation., Results: In the septic shock model, ICH3 revealed antipyretic action and reduced the surge of circulating cytokines. In vitro, ICH3 stimulation (10 µM) preserved viability of human adipocytes, decreased IL-6 mRNA (P < 0.05) and blunted LPS-induced peak of TNFα (P < 0.05) and IL-6 (P < 0.01). Chronic administration of ICH3 to DIO mice was associated with lower numbers of CD8+ T cells (P < 0.05) and to changed WAT expression of inflammatory factors (Hp, P < 0.05; CD301/MGL1, P < 0.01; Arg-1, P < 0.05). As compared to untreated, ICH3 DIO mice exhibited improved insulin signaling in the skeletal muscle (P < 0.01) mirrored by an improved response to glucose load (ipGTT: P < 0.05 at 120 min)., Conclusions: We proved that ICH3 is an anti-inflammatory drug, able to reduce inflammatory cytokines in human adipocytes and to blunt the effects of obesity on WAT inflammatory profile, on glucose tolerance and on tissue insulin sensitivity.

Primary effusion lymphoma (PEL) is defined as a HHV-8-associated large B-cell lymphoma, which favors HIV-infected young adults, typically presenting as a serous (pleural, pericardial, or peritoneal) effusion with no identifiable tumor mass. Uncommon instances of lymphoid proliferations with the same morphology, immunophenotype, and molecular features as PEL, but occurring as a solid tumor mass without serous cavities involvement, have been termed extracavitary (or solid) variant of PEL. We hereby report the exceptional case of a HIV-associated extracavitary PEL primarily localized to the skin and exhibiting a panniculitis-like presentation. Primary cutaneous presentation of extracavitary PEL is exceedingly uncommon, with only 6 cases previously described in the literature. In light of its atypical immunophenotype, the differential diagnosis in case of skin involvement by extracavitary PEL is challenging: demonstration of HHV-8 infection in neoplastic cells is of pivotal importance. Our case is further atypical in that the lymphoid proliferation underwent complete and protracted regression solely by establishment of highly active antiretroviral therapy.

Scope: To assess the individual effects of dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on insulin resistance (IR), gut microbiome, and gut metabolites in high-fat-diet-induced obese (DIO) mice., Methods and Results: DIO mice are fed an either high-fat diet (HFD), EPA (1% w/w) enriched HFD, or DHA (1% wt/wt) enriched HFD for 15 weeks. Both EPA and DHA supplements reverse hyperglycemia and IR but do not affect body weight in DIO mice while DHA exhibits a more pronounced ameliorative effect in male mice. Both EPA- and DHA-enriched Lactobacillus and short-chain fatty acids (SCFAs)-producing species from Lachnospiraceae while reduced lipopolysaccharide (LPS)-producing Bilophila and Escherichia/Shigella. Compared with EPA, DHA-supplemented mice have more abundant propionic/butyric acid-producing bacteria, including Coprococcus, Butyricimonas synergistica, Bacteroides acidifaciens, and Intestinimonas, and less-abundant LPS-correlated species Streptococcus and p-75-a5. The shifts in gut microbiome co-occurred with the changes in levels of propionic/butyric acid, circulating LPS, and serotonin. Additionally, EPA/DHA supplementation attenuates adipose inflammation with upregulated glucose transporter 4 and Akt phosphorylation, indicating the improvement of insulin signaling., Conclusion: EPA and DHA differentially reverse IR and relieve adipose inflammation while modulating gut microbiome and SCFAs/LPS production, underscoring the gut-adipose axis as a primary target of EPA/DHA., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Dermatomyositis is an idiopathic muscle disease characterized by proximal muscle weakness, raised muscle enzymes, characteristic changes in electromyography and typical skin rash and biopsy findings. Dermatological features like Gottron's sign and papules are considered as pathognomonic for dermatomyositis. Panniculitis is one of the rare findings in dermatomyositis. Here, we report a case of dermatomyositis in 37 years old female who presented with only panniculitis and the diagnosis was delayed by more than a year.

A captive, adult female Brent goose ( Branta bernicla ) with a history of severe feather picking by its mate, was presented with 0.5-2.5 cm skin nodules on the head and neck. Histologic examination revealed a well-delineated dermal mass that surrounded an intact feather follicle and was composed of lakes of proteinaceous fluid and fibrin with scattered foamy macrophages and multinucleate giant cells. No bacteria or fungi were identified with histology, microbial culture, or PCR. Sterile panniculitis is an infrequent finding in animals and traumatic panniculitis is rarely sterile.

Scope: Two hydrogenated xanthohumol (XN) derivatives, α,β-dihydro-XN (DXN) and tetrahydro-XN (TXN), improved parameters of metabolic syndrome (MetS), a critical risk factor of cardiovascular disease (CVD) and type 2 diabetes, in a diet-induced obese murine model. It is hypothesized that improvements in obesity and MetS are linked to changes in composition of the gut microbiota, bile acid metabolism, intestinal barrier function, and inflammation., Methods and Results: To test this hypothesis, 16S rRNA genes were sequenced and bile acids were measured in fecal samples from C57BL/6J mice fed a high-fat diet (HFD) or HFD containing XN, DXN or TXN. Expression of genes associated with epithelial barrier function, inflammation, and bile acid metabolism were measured in the colon, white adipose tissue (WAT), and liver, respectively. Administration of XN derivatives decreases intestinal microbiota diversity and abundance-specifically Bacteroidetes and Tenericutes-alters bile acid metabolism, and reduces inflammation. In WAT, TXN supplementation decreases pro-inflammatory gene expression by suppressing macrophage infiltration. Transkingdom network analysis connects changes in the microbiota to improvements in MetS in the host., Conclusion: Changes in the gut microbiota and bile acid metabolism may explain, in part, the improvements in obesity and MetS associated with administration of XN and its derivatives., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report the case of an otherwise healthy 60-year-old man presenting with fever, leucocytosis and a painful swelling of the right calf. We initially performed cultural and cytological examination of the popliteal fossa mass, but the results were disappointingly inconclusive. The subsequent development of several erythematous subcutaneous nodules, rapidly evolving to broad ulcerative lesions, prompted us to reconsider the clinical setting as a whole, which included fever, marked leucocytosis and multiple subcutaneous nodules. A biopsy of the ulcerative lesions finally led to the diagnosis of neutrophilic panniculitis, which was sustained by a hybrid myelodysplastic/myeloproliferative disorder like BCR-ABL1-negative atypical chronic myeloid leukaemia. The patient was initially treated with high-dose intravenous corticosteroids, resulting in a dramatic improvement of the skin lesions and normalisation of blood tests. Azacytidine treatment was subsequently started, and the haematological disease remained stable., Competing Interests: Competing interests: Not required., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

We present a rare case of pancreatic panniculitis in a 59-year-old male simultaneous pancreas-kidney (SPK) recipient with failed allografts. The patient presented with fever and painful erythematous nodules on his leg 1 month after stopping all immunosuppression. A thorough infectious and rheumatological workup was negative. He had pancreas rejection 4 years after SKP transplant and was restarted on dialysis after 14 years when his renal allograft failed due to chronic allograft nephropathy. His chronic immunosuppression (tacrolimus, azathioprine) was stopped and prednisone was weaned over 3 months at that time. A skin biopsy revealed saponification of the subcutaneous fat with inflammation pathognomonic of pancreatic panniculitis. Concurrent allograft pancreatitis confirmed with elevated lipase and a computed tomography scan finding of peripancreatic graft stranding and atrophic native pancreas. He was started on pulse steroid therapy for 3 days followed by oral taper. This resulted in dramatic resolution of all skin lesions and normalization of lipase levels within 1 week, followed by resumption of low-dose tacrolimus and azathioprine. This is an extremely rare occurrence of panniculitis in pancreas allograft after 10 years of pancreatic failure associated with stopping immunosuppression., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)