Abdominal Fat Biopsy Research Articles

Accelerated subcutaneous abdominal stem cell adipogenesis predicts insulin sensitivity in normal-weight women with polycystic ovary syndrome

To examine whether subcutaneous (SC) abdominal adipose stem cell differentiation into adipocytes invitro predicts insulin sensitivity (Si) invivo in normal-weight women with polycystic ovary syndrome (PCOS) and controls. Prospective cohort study. Academic medical center. Eight normal-weight women with PCOS and 8 age- and body mass index-matched controls. Women underwent circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total-body dual-energy x-ray absorptiometry, and SC abdominal fat biopsy. PPARγ and CEBPa gene expression and lipid content of adipocytes matured invitro were compared between women with PCOS and control women, and correlated with patient characteristics, systemic Si, and adipose insulin resistance (adipose-IR). Serum androgen levels, adipose-IR, and percentage of android fat were greater in women with PCOS than control women. Stem cell PPARγ and CEBPa gene expression increased maximally by day 12 without a female-type effect. In control cells, gene expression positively correlated with fasting serum insulin levels (both genes) and adipose-IR (CEBPa) and negatively correlated with Si (CEBPa). Conversely, CEBPa gene expression in PCOS cells negatively correlated with adipose-IR and serum free testosterone, whereas total lipid accumulation in these cells positively corelated with Si. In normal-weight women with PCOS, accelerated SC abdominal adipose stem cell differentiation into adipocytes invitro favors Si invivo, suggesting a role for hyperandrogenism in the evolution of metabolic thrift to enhance fat storage through increased cellular glucose uptake.

P0307KIDNEY-HEMOPATHY CONSULTATION: A SINGLE-CENTER EXPERIENCE

Abstract Background and Aims Renal involvement in plasma cell dyscrasia has been widely described, including Monoclonal Gammopathy of Renal significance (MGRS). Chronic kidney disease (CKD) in hematological disorders carries major implications for management, prognosis and the potential for progressive renal injury and ESRD. Specific monthly Kidney-Hemopathy Consultation has been created in 2017 in the department of Nephrology. The aimed of this was to describe the clinical, biological and histological characteristics of patients with hematological disorders and CKD. Method From 01/05/2017 to 31/12/2019 adults with hematological disorders and CKD (eGFR<60ml/min and/or proteinuria or hematuria) were prospectively included. Results Fifty-six patients (27 men) were enrolled: Multiple Myeloma (n=30), MGUS (n=11), Lymphoma (n=5), Acute Leukemia (n=4), LMC (n=2), 1 LLC (n=2), Cryoglobulinemia (n=1), Refractory Anemia with Excess blasts (n=1), Bone marrow aplasia (n=1). This nephrology consultation was the first for 22 patients (39%), referred by a hematologist in 38 cases (68%). Renal injury was confirmed after the hematologic diagnosis in 34 patients (61%) and precedes the diagnosis of plasma cell dyscrasia for 8 patients (14%). The median eGFR was 54.1ml/min/1.73m (128-4): CKD stage II (n=16), stage III (n=28), stage IV (n=7) and stage V (n=2). Proteinuria was >0.5g/day for 22 (39.3%) patients including a Bence-Jones proteinuria for 15 patients (27%). Acute Kidney Injury (AKI) was confirmed in 34 patients (63%) and 8 (24%) requiring acute dialysis. Histologic diagnostic of kidney injury was confirmed for 21 patients (38%): 16 kidney biopsies and 5 AL renal amyloidosis confirmed by salivary glands or abdominal fat biopsy. MGRS was confirmed in 34 patients (61%): Cast nephropathy (n=10;29%), AL amyloidosis (n=7;20%); C3 nephropathy (n=3; 9%), Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits (n=3), Light Chain Proximal Tubulopathy (n=3), Randall-type monoclonal immunoglobulin deposition disease (n=2, 6%), 1 Minimal Change Disease (n=1; 3%), Glomerulonephritis with Organized Microtubular Monoclonal Ig Deposits (n=1) and exclusive tumoral renal infiltration (n=1). Associated tumoral infiltration or crystalline podocytopathy was confirmed in 2 and 1 biopsy respectively. Glomerular MGRS was highly suspected for 2 patients, even if no biopsy was performed. MGRS was excluded for 22 patients (39%): AKI due to antibiotics or sepsis (n=8; 36%), hypovolemia (n=4; 18%) or hypercalcemia (n=3; 14%); 2 renal artery stenosis due to tyrosine kinase inhibitors (n=2; 9%), nephroangiosclerosis (n=1), lithiasis (n=1), CKD post- nephrectomy CKD (n=1), and immunoallergic nephritis (n=1). Hematological treatment was initiated in 54 patients (96%). All patients with MGRS were treated, whom 17 (50%) completely or partially in the Nephrology department. Proteasome inhibitors, alkylant agents and IMIDs were the main molecule used in first line therapy (56%, 23% and 12% respectively). Eleven patients (20%) had stem cell transplantation. After a median follow up of 16 months (38-0), complete or very good partial hematologic response was obtained in 48 patients (89%); whom 30 with MGRS (88%). Median eGFR was 45ml/min/1.73m (142-4): CKD stage II (n=18), stage III (n=23) and stage IV (n=9). Only 1/3 CKD stade V patient needed chronic replacement therapy. Eight patients died (14%): 4 uncontrolled hematologic disease (50%) and 3 septic complications (38%). Conclusion Very closed collaboration between Nephrology and Hematology Department in our Center contributes to improve early management of patients with hematological disorders associated with CKD, and probably their survey. Hemato-Nephrology is a viable and emergent specialty.

1987-P: Inflammation and Insulin Resistance in Adipose Tissue

Background: Adipose tissue inflammation is linked to adipose tissue insulin resistance. However, whether this is a causal relationship remains controversial. Therefore, we aimed to explore the relationship between measures of adipose tissue inflammation and adipose tissue insulin sensitivity over a wide range of body fat distribution and adipose tissue insulin sensitivity. Methods: We recruited a total of 87 volunteers (30 men and 57 women). Adipose tissue insulin sensitivity was quantified as the insulin concentration required for a 50% suppression of lipolysis (IC50). Lipolysis was measured as steady-state palmitate flux before and during a hyperinsulinemic-euglycemic clamp. Adipose tissue macrophage (ATM) was quantified by immunohistochemistry with antibodies against CD68 (total ATM), CD14 (pro-inflammatory ATM) and CD206 (anti-inflammatory ATM) and senescent preadipocyte content was quantified by β-galactosidase positivity using fluorescent microscopy in abdominal and femoral fat biopsies. Results: Total ATM content was only weakly associated with IC50 in abdominal fat (r=0.26, p=0.01) and no association was observed for femoral fat. No association was observed between IC50 and pro-inflammatory ATM content. Anti-inflammatory ATM content was associated with IC50 in abdominal (r=0.46, p<0.001) and femoral (r=0.33, p=0.02) fat. Senescent preadipocyte content was weakly associated with IC50 in femoral fat (r=0.36, p=0.01), but no association was observed in abdominal fat. Fat cell size was strongly associated with IC50 in both abdominal (r=0.6 p<0.001) and femoral (r=0.48, p<0.01) fat. Conclusions: ATM content is only weakly associated to adipose tissue insulin sensitivity. Only the content of anti-inflammatory, not pro-inflammatory macrophages, was associated with adipose tissue insulin sensitivity. This argues against pro-inflammatory macrophages as mediators of insulin resistance in adipose tissue. Disclosure E. Søndergaard: None. A.E. Espinosa De Ycaza: None. M. Morgan-Bathke: None. K. Lytle: None. D.A. Delivanis: None. B.G. Carranza Leon: None. M.D. Jensen: None. Funding National Institutes of Health (DK40404, DK45343)

Fat Distribution in Women Is Associated With Depot-Specific Transcriptomic Signatures and Chromatin Structure.

BackgroundPreferential accumulation of fat in the upper body (apple shape) is associated with higher risk of developing metabolic syndrome relative to lower body fat (pear shape). We previously discovered that chromatin openness partially defined the transcriptome of preadipocytes isolated from abdominal and gluteofemoral fat. However, the molecular mechanisms underlying interindividual variation in body shape are unknown.MethodsAdipocyte fraction was isolated from abdominal and gluteofemoral fat biopsies of premenopausal women (age and body mass index matched) segregated initially only by their waist-to-hip ratio. We evaluated transcriptomic and chromatin accessibility using RNA sequencing and assay for transposase-accessible chromatin using sequencing (ATAC-seq) along with key clinical parameters.ResultsOur data showed that higher lower body fat mass was associated with better lipid profile and free fatty acid decrease after glucose administration. Lipid and glucose metabolic pathways genes were expressed at higher levels in gluteofemoral adipocyte fraction in pears, whereas genes associated with inflammation were higher both in abdominal and gluteofemoral apple adipocyte fraction. Gluteofemoral adipocyte chromatin from pear-shaped women contained a significantly higher number of differentially open ATAC-seq peaks relative to chromatin from the apple-shaped gluteofemoral adipocytes. In contrast, abdominal adipocyte chromatin openness showed few differences between apple- and pear-shaped women. We revealed a correlation between gene transcription and open chromatin at the proximity of the transcriptional start site of some of the differentially expressed genes.ConclusionsIntegration of data from all 3 approaches suggests that chromatin openness partially governs the transcriptome of gluteofemoral adipocytes and may be involved in the early metabolic syndrome predisposition associated with body shape.

Resveratrol and metabolic health in COPD: A proof-of-concept randomized controlled trial.

Patients with COPD are often characterized by disturbed metabolic health which is reflected in altered body composition. Current studies in healthy subjects suggest that resveratrol improves metabolic health by enhancing muscle mitochondrial function and adipose tissue morphology. The primary objective was to investigate the effect of four weeks resveratrol supplementation on muscle mitochondrial function in patients with COPD. Secondary objectives were to investigate the effect of resveratrol on adipose tissue inflammatory and metabolic gene expression, systemic inflammation and body composition in patients with COPD. In a double-blind randomized placebo-controlled proof-of-concept study, 21 COPD patients (FEV1: 53±15% predicted; age: 67±9 years and BMI: 24.5±3.3kg/m2) received resveratrol (150mg/day) or placebo for four weeks. Before and after intervention, blood samples, quadriceps muscle and subcutaneous abdominal fat biopsies were obtained for metabolic and inflammatory profiling. Body composition was assessed by dual energy X-ray absorptiometry. Muscle mitochondrial biogenesis regulators AMPK, SIRT1 and PGC-1α as well as mitochondrial respiration, Oxphos complexes, oxidative enzyme activities and kynurenine aminotransferases were not improved by resveratrol. Plasma high-sensitive C-reactive protein and kynurenine did not change after resveratrol supplementation. Adipose tissue inflammatory markers were unaffected by resveratrol, while markers of glycolysis and lipolysis were significantly increased compared to placebo supplementation. Body weight decreased after resveratrol supplementation (resveratrol-0.95±1.01kg vs placebo-0.16±0.66kg, p=0.049) due to a reduction in lean mass (resveratrol-1.79±1.67kg vs 0.37±0.86kg, p=0.026). We do not confirm previously reported positive effects of resveratrol on skeletal muscle mitochondrial function in patients with COPD, but show an unexpected decline in lean mass. Clinicaltrials.gov NCT02245932.

Testosterone Increases the Expression and Phosphorylation of AMP Kinase α in Men With Hypogonadism and Type 2 Diabetes.

Adenosine 5'-monophosphate-activated protein kinase-α (AMPKα) is a mediator of exercise-induced glucose uptake in skeletal muscle. We evaluated whether AMPKα expression and phosphorylation are reduced in skeletal muscle and adipose tissue of patients with hypogonadotropic hypogonadism (HH), and whether testosterone replacement therapy results in restoration of the expression and phosphorylation of AMPKα. This is a secondary analysis of a previously completed trial that showed an insulin-sensitizing effect of testosterone therapy in men with type 2 diabetes and HH. Clinical research center at university. Thirty-two men with HH and 32 eugonadal men were compared at baseline. Men with HH were treated with intramuscular injections of testosterone or placebo every 2 weeks for 22 weeks. Quadriceps muscle biopsies and subcutaneous abdominal fat biopsies were obtained before and after 4-hour euglycemic hyperinsulinemic clamp, prior to and after testosterone or placebo therapy. mRNA expression of AMPKα in hypogonadal men was lower by 37% in adipose tissue and 29% in skeletal muscle, respectively, compared with levels in eugonadal men, while phosphorylated AMPKα was lower by 22% and 28%, respectively. Following testosterone replacement, the expression of AMPKα did not alter in the fasting state but increased markedly by 41% and 46% in adipose tissue and muscle, respectively, after the clamp. In contrast, phosphorylated AMPKα increased by 69% in muscle after testosterone therapy but did not change following the clamp. Testosterone modulates the expression of AMPKα and phosphorylated AMPKα. These effects may contribute to the improved insulin sensitivity following testosterone therapy.

Brief Report: Adipogenic Expression of Brown Fat Genes in HIV and HIV-Related Parameters.

Persons with HIV are at increased risk for adipose dysfunction, which could mediate metabolic complications such as cardiovascular disease, fatty liver disease, and diabetes. We have previously reported reduced browning and beiging capacity of the subcutaneous adipose depot in HIV. We sought to evaluate how HIV-related parameters are related to the expression of brown and beige fat genes in the abdominal subcutaneous adipose tissue. Eighteen persons with HIV underwent punch biopsy of abdominal subcutaneous fat to determine mRNA expression of adipose-related genes using quantitative reverse transcriptase-polymerase chain reaction. Duration of antiretroviral therapy use, particularly related to protease inhibitor use, was significantly related to reduced expression of multiple brown and beige fat genes (including UCP1, PGC1α, PRDM16 and others, all P ≤ 0.04) in the abdominal subcutaneous fat. In addition, duration of HIV and CD4 T-cell count were significantly correlated with reduced expression of multiple brown and beige fat genes in the abdominal subcutaneous fat (PGC1α, P2XR5, TMEM26, CD137, all P ≤ 0.05 for duration of HIV; and PGC1α, ZIC1, PRDM16, PAT2, P2RX5, TMEM26, CD137, all P ≤ 0.04). In contrast, HIV viral load did not correlate with any brown or beige fat genes. Key HIV-related parameters reflective of nonacute infection (increased duration of HIV and duration of antiretroviral therapy use) or relatively reduced immunologic function (lower CD4 count) were linked to reduced expression of brown and beige fat gene in the abdominal subcutaneous adipose depot. NCT01098045.

Amyloid associated infiltrative cardiomyopathy with Waldenstrom’s Macroglobulinemia

Amyloid associated infiltrative cardiomyopathy with Waldenstrom’s Macroglobulinemia - IJPO- Print ISSN No: - 2394-6784 Online ISSN No:- 2394-6792 Article DOI No:- 10.18231/j.ijpo.2019.135, Indian Journal of Pathology and Oncology-Indian J Pathol Oncol

1617 Colon Ischemia as Initial Presentation of Amyloidosis: A Rare and Challenging Diagnosis

INTRODUCTION: Amyloidosis is a systemic disease rarely involving gastrointestinal tract (GIT) and requires a high index of suspicion to diagnose. GI presentations including abdominal pain, bleeding, malabsorption or protein losing enteropathy. Predisposing conditions are plasma cell dyscrasia, chronic inflammatory conditions or hemodialysis. We present case of Amyloidosis involving entire GIT presented with severe colon ischemia required total colectomy. CASE DESCRIPTION/METHODS: A 59-year-old man with 6 months history of abdominal pain, bloating and constipation. He tried laxatives with partial relief. A colonoscopy revealed ulcerations in the sigmoid colon with biopsies consistent with ischemic colitis. CT angiography of the abdomen showed patent vessels with no findings to explain ischemic changes. A colonoscopy repeated 3 months later showed persistent inflammation in the sigmoid colon. He, subsequently, was diagnosed with multiple myeloma and initiated on bortezomib and dexamethasone. A few weeks after initiating this treatment, he presented to ED with significantly worsened abdominal pain, distension and nausea. CT A/P revealed thickening from the rectum to the descending colon with proximal dilation, concerning for pneumatosis and ischemic colitis. He was taken emergently for a total colectomy with end ileostomy. Pathology revealed that he, in fact, had extensive amyloidosis (transmural, interstitial, and vascular involvement) with hemorrhage and necrosis throughout the removed colon as well as the removed portion of the ileum with positive margins. There have been prior reports of colonic ischemia after initiation of bortezomib however this does not appear to be culprit in this case given the patient’s findings on initial colonoscopy prior to starting the medication. DISCUSSION: Amyloid deposition infiltrates multiple organs. GIT involvement is common, rectal biopsy can confirm diagnosis. However, severe colon ischemia is uncommon presentation. Our patient presented with severe ischemic colitis and pneumatosis on CT scan. Prior to this, he had 2 colonoscopies, EGD, and abdominal fat biopsy all was non-diagnostic. He subsequently, had total colectomy, pathology revealed Amyloidosis. Duodenal biopsies confirmed small intestine amyloidosis. Colon ischemia due to Amyloidosis is rare. Diagnosis is challenging but can lead to detrimental consequences when it is delayed. Early diagnosis is critical in preventing progressive disease and potentially fatal complications.

Une maladie systémique mimant une polyarthrite rhumatoïde

IntroductionRare systemic diseases such as amyloidosis can mimic inflammatory rheumatic diseases. Because of their poor prognosis, physicians should rule them out at the onset of inflammatory rheumatism. We report a case of AL amyloidosis misdiagnosed as rheumatoid arthritis. Case reportA 71-year-old woman was referred for seronegative rheumatoid arthritis, resistant to three biologic therapies. She had an IgA lambda monoclonal gammopathy of undetermined significance (MGUS). The patient subsequently developed glomerular proteinuria. Abdominal fat and accessory salivary glands biopsies revealed amyloid light-chain (AL) amyloidosis. Treatment with bortezomib–cyclophosphamide–dexamethasone, led to complete hematologic, renal and rheumatologic remission. Ten months after treatment interruption, the patient had an articular and hematologic relapse. ConclusionAmyloid light-chain amyloidosis arthropathy is probably underdiagnosed. A review of amyloid arthropathy associated with multiple myeloma found that 33% of patients had been misdiagnosed with rheumatoid arthritis.

Molecular adaptation in adipose tissue in response to overfeeding with a high-fat diet under sedentary conditions in South Asian and Caucasian men.

For the same BMI, South Asians have a higher body fat percentage than Caucasians. There might be differences in the fatty acid (FA) handling in adipose tissue when both ethnicities are exposed to high-fat overfeeding. The objective of the present study was to investigate the molecular adaptation in relation to FA metabolism in response to overfeeding with a high-fat diet (OHFD) in South Asian and Caucasian men. Ten South Asian men (BMI 18-29 kg/m2) and ten Caucasian men (BMI 22-33 kg/m2), matched for body fat percentage, aged 20-40 years were included. A weight-maintenance diet (30 % fat, 55 % carbohydrate and 15 % protein) was given for 3 d followed by 3 d of overfeeding (150 % energy requirement) with a high-fat diet (60 % fat, 25 % carbohydrate and 15 % protein) while staying in a respiration chamber. Before and after overfeeding, abdominal subcutaneous fat biopsies were taken. Proteins were isolated, analysed and quantified for short-chain 3-hydroxyacyl-CoA dehydrogenase (HADH), carnitine palmitoyl-transferase 1α (CPT1a), adipose TAG lipase, perilipin A (PLINA), perilipin B, lipoprotein lipase and fatty acid binding protein 4 using Western blotting. OHFD decreased the HADH level (P < 0·05) in Caucasians more than in Asians (P < 0·05), but the baseline and after intervention HADH level was relatively higher in Caucasians. The level of CPT1a decreased in South Asians and increased in Caucasians (P < 0·05). PLINA did not change with diet but the level was higher in South Asians (P < 0·05). The observed differences in HADH and PLINA levels as well as in CPT1a response may be important for differences in the long-term regulation of energy (fat) metabolism in these populations.

Prevalence of cardiac amyloidosis among adult patients referred to tertiary centres with an initial diagnosis of hypertrophic cardiomyopathy

BackgroundDifferential diagnosis of genetic causes of left ventricular hypertrophy (LVH) is crucial for disease-specific therapy. We aim to describe the prevalence of Cardiac Amyloidosis (CA) among patients ≥40 years with an initial diagnosis of HCM referred for second opinion to national cardiomyopathy centres. MethodsConsecutive patients aged ≥40 years referred with a tentative HCM diagnosis in the period 2014–2017 underwent clinical evaluation and genetic testing for HCM (including trans-thyretin-TTR). Patients with at least one red flag for CA underwent blood/urine tests, abdominal fat biopsy and/or bone-scintigraphy tracing and eventually ApoAI sequencing. ResultsOut of 343 patients (age 60 ± 13 years), 251 (73%) carried a likely/pathogenic gene variant, including 12 (3.5%) in the CA-associated genes TTR (n = 11) and ApoAI (n = 1). Furthermore, 6 (2%) patients had a mutation in GLA. Among the remaining, mutation-negative patients, 26 with ≥1 CA red-flag were investigated further: 3 AL-CA and 17 wild-type-TTR-CA were identified. Ultimately, 32(9%) patients were diagnosed with CA. Prevalence of CA increased with age: 1/75 (1%) at age 40–49, 2/86 (2%) at age 50–59, 8/84 (9%) at age 60–69, 13/61 (21%) at age 70–79, 8/31 (26%) at age ≥80 (p for trend <0.01). ConclusionsAmong patients referred with and initial diagnosis of HCM, CA was the most common unrecognized mimic (9% prevalence) and increased with age (from 1% at ages 40–49 years to 26% >80 years). Age at diagnosis should be considered one of the most relevant red flags for CA in patients with HCM phenotypes; however, there is no clear age cut-off mandating scintigraphy and other second level investigations in the absence of other features suggestive of CA.

MON-223 Adipose Insulin Resistance in Normal-Weight Women with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and oligo-ovulation associated with insulin resistance (IR). Adipose-IR may underlie this PCOS phenotype and could contribute to IR by impairing insulin-mediated glucose uptake and/or lipogenesis, while diminishing insulin suppression of lipolysis. The present study examined whether adipose-IR, defined as the product of fasting circulating free fatty acid and insulin levels (1), was increased in normal-weight PCOS versus age-/BMI-balanced normo-androgenic ovulatory (control) women and, if so, whether it correlated with insulin sensitivity (Si) as measured by frequently-sampled intravenous glucose tolerance testing (FSIVGTT) and/or hyperandrogenism. Ten normal-weight PCOS women (by NIH criteria) and 18 controls (19-35 years; 19-25 kg/m2) of non-Hispanic Caucasian descent underwent serum hormone/metabolic measurements, FSIVGTT, total body dual-energy x-ray absorptiometry, and subcutaneous (SC) abdominal fat biopsy. Circulating hormone/metabolite levels, adipose-IR, Si, acute insulin response to glucose (AIRg), body fat distribution and adipocyte size distribution were compared between female types using Student’s t-test. Partial correlation coefficients examined associations between adipose-IR and outcome variables, adjusting for serum androgen levels. PCOS women exhibited greater serum LH, androstenedione (A4), total testosterone (T) and free (f) T levels than controls (P<0.05, all parameters), and demonstrated trends for increased abdominal adiposity (P=0.06) and serum triglyceride (TG) levels (P=0.09) with low-normal Si values. PCOS women also had greater (P=0.007) adipose-IR than controls, with a value of 29 pM/L*mM/L providing 94% specificity (95% CI 84%-100%) and 80% sensitivity (95% CI 55%-100%) in discriminating PCOS subjects from controls (AUC=0.81, 95% CI 0.61-1.00, P<0.001). In all women combined, adipose-IR negatively correlated with Si (P=0.01) and positively correlated with serum A4 (P=0.002), total T (P=0.004), fT (P=0.001) and fasting TG (P=0.001) levels as well as with AIRg (P=0.03) and percent small SC abdominal adipocytes (P=0.01). Relationships of adipose-IR with Si (P=0.04) and with serum TG (P=0.01) levels remained after adjusting for serum total T and fT levels, respectively, while the other correlations lost significance. Thus, in normal-weight PCOS women, adipose-IR is intimately linked with dyslipidemia and is associated with reduced Si in part through hyperandrogenism. Reference: Sondergaard E, et al. JCEM 2017;102:1193. Sources of Research Support: NIH Grants and Santa Monica Bay Woman’s Club.

Od monoklonalnej gammapatii o nieokreślonym znaczeniu (MGUS) do szpiczaka plazmocytowego i amyloidozy — opis przypadku

We present a 69-year-old patient, in whom in March 2016 a monoclonal gammopathy of undetermined significance (MGUS) was diagnosed. The disease was found during the diagnostics of thrombocytopenia (from 2009 the number of platelets varied between 90–140 G/l). In serum immunofixation assay the presence of monoclonal IgG kappa protein was confirmed. In July 2017, when the patient presented with nephrotic syndrome and acute renal failure, 14.5% of plasma cells were found in the bone marrow. Moreover, a biopsy of abdominal fat revealed the presence of amyloid composed of kappa light chains. The diagnosis of IgG kappa plasma cell myeloma (PCM) complicated with amyloidosis of the kidneys, heart, liver and spleen was established. The PCM progression complicated with amyloidosis was very aggressive. Despite the treatment with bortezomib and dexamethasone the patient died early. Sudden deterioration of health (e.g. in the form of acute renal failure) in a patient with MGUS may indicate not only the progression of MGUS to PCM, but also the development of amyloidosis, which is associated with turbulent disease and poor prognosis.

Incidental multiple adenopathies and the diagnosis of systemic amyloidosis

This report describes the clinical case of a 67-yearold man with hypertension referenced to the medical consultation for the study of several bilateral mediastinal adenopathies discovered accidentally on a chest computed tomography (CT) following the patient’s admission to the emergency department after falling off a tree. Of note in the physical examination is the presence of macroglossia and thick lips (Figure 1A). In the complementary study of adenopathies serologic data and a positron emission tomography (PET) scan were requested. Analytically with a sedimentation rate of 21 mm, the peripheral blood smear analysis was normal and there was a good renal function with no change in phosphocalcic metabolism. At the level of immunoglobulins, a value of IGG-2300 mg/dl was found with the respective gamma-monoclonal peak (IGG-lambda) in the electrophoresis allowing the diagnosis of monoclonal gammopathy of undetermined significance. Posteriorly, PET scan demonstrated additional cervical and mediastinum-hilar bilateral ganglia with low metabolic activity of inflammatory nature, without suggestive alterations of tumor lesions with significant hypermetabolism of 18F-FDG (Figure 1B, Figure 1C). The definitive diagnosis of primary amyloidosis was obtained later through abdominal fat biopsy (Figure 1D). An echocardiogram was requested to rule out the cardiac involvement of the disease. Given the clinical stability of the patient and the absence of significant findings in the complementary diagnostic tests, the strategy adopted in this patient was “watch and see.”

Molecular adaptations in human subcutaneous adipose tissue after ten weeks of endurance exercise training in healthy males.

Endurance exercise training induces adaptations in metabolically active organs, but adaptations in human subcutaneous adipose tissue (scAT) remains incompletely understood. On the basis of animal studies, we hypothesized that endurance exercise training would increase the expression of proteins involved in lipolysis and glucose uptake in scAT. To test these hypotheses, 19 young and healthy males were randomized to either endurance exercise training (TR; age 18-24 yr; BMI 19.0-25.4 kg/m2) or a nonexercising control group (CON; age 21-35 yr; BMI 20.5-28.8 kg/m2). Abdominal subcutaneous fat biopsies and blood were obtained at rest before and after intervention. By using Western blotting and PCR, we determined expression of lipid droplet-associated proteins, various proteins involved in substrate metabolism, and mRNA abundance of cell surface G protein-coupled receptors (GPCRs). Adipose tissue insulin sensitivity was determined from fasting plasma insulin and nonesterified fatty acids (adipose tissue insulin resistance index; Adipo-IR). Adipo-IR improved in TR compared with CON ( P = 0.03). This was accompanied by increased insulin receptor (IR) protein expression in scAT with a 1.54-fold (SD 0.79) change from baseline in TR vs. 0.85 (SD 0.30) in CON ( P = 0.007). Additionally, hexokinase II (HKII) and succinate dehydrogenase complex subunit A (SDHA) protein increased in TR compared with CON ( P = 0.006 and P = 0.04, respectively). We did not observe changes in lipid droplet-associated proteins or mRNA abundance of GPCRs. Collectively, 10 weeks of endurance exercise training improved adipose tissue insulin sensitivity, which was accompanied by increased IR, HKII, and SDHA protein expression in scAT. We suggest that these adaptations contribute to an improved metabolic flexibility. NEW & NOTEWORTHY This study is the first to investigate the molecular adaptations in human subcutaneous adipose tissue (scAT) after endurance exercise training compared with a nonexercising control group. We show that endurance exercise training improves insulin sensitivity in human scAT, and this is accompanied by increased expression of insulin receptor, hexokinase II, and succinate dehydrogenase complex subunit A. Collectively, our data suggest that endurance exercise training induces molecular adaptations in human scAT, which may contribute to an improved metabolic flexibility.

A Study on the Immunological Changes in Adult Male Obese Rats and the Possible Immune Modulator Effect of Conjugated Linoleic Acid Supplementation

AbstractBackground: Conjugated Linoleic Acid [CLA] is suggested as a novel drug to improve obesity.Objectives: The aim of this study was to elucidate the possible role of CLA in ameliorating the pathophysiology in obese rats and modulate its immune function.Methods: Forty adult male albino rats of local strain, weighing [120-160] grams each, were used. Rats were ran-domly divided into five equal experimental groups, control, CLA-supplemented, obese, CLA-prophylactic obese and CLA-treated obese groups obesity was induced by High Fat Diet [HFD] for 12 weeks. CLA was administered orally in a dose of 1500mg/kg body weight for 12 weeks. Initial and final Body Weight (BW) and Body Mass Index (BMI) and food intake were measured. Total Leucocytic Count (TLC) and its differential count and serum Tumor Necrosis Factor-alpha (TNF-a) were measured. Visceral fat and total white abdominal fat to each 100 [gm]/BW were measured. Caspase 3 expression was evaluated in the abdominal fat biopsies using immuno-histochemistry.Results: High fat diet resulted in deterioration and impair-ment of most measured parameters. CLA supplementation decreased final BW of obese rats, food intake, visceral fat, and total abdominal together with increased CD8+, CD4+ T lymphocytes and eosinophilic %. Moreover, CLA supplemen-tation decreased TNF-a in CLA-supplemented and CLA-prophylactic groups but not in CLA-treated group. High fat diet increased TLC and CD4+ T lymphocytes but decrease eosinophilic % and CD8+ T lymphocytes. In addition, CLA increased the positivity of caspase 3 in CLA-prophylactics and CLA-treated obese groups.Conclusion: CLA supplementation, either as a prophylactic agent or a therapeutic one, to the high fat feed rats could ameliorate most of the detrimental effects of obesity, particu-larly those related to the immune system. This beneficial effect of CLA could be explained by its immune modulator, anti-inflammatory and pro apoptotic effects.

Precocious subcutaneous abdominal stem cell development to adipocytes in normal-weight women with polycystic ovary syndrome

To examine whether abnormal subcutaneous (SC) abdominal adipose stem cell (ASC) development to adipocytes in polycystic ovary syndrome (PCOS) correlates with hyperandrogenism. Prospective cohort study. Academic medical center. Eight normal-weight women with PCOS and eight normoandrogenic ovulatory (control) women matched for age and body mass index. Circulating hormone and metabolic measurements, intravenous glucose tolerance testing, total body dual-energy X-ray absorptiometry, and SC abdominal fat biopsy. Invitro ASC commitment to preadipocytes (ZFP423 protein expression, day 0.5), preadipocyte differentiation to adipocytes (PPARγ gene expression, day 3) and adipocyte lipid content (Oil-Red-O fluorescence, day 12) comparisons correlated with clinical outcomes. In women with PCOS, SC abdominal ASCs compared with those of control women showed exaggerated commitment to preadipocytes and had greater lipid content in newly formed adipocytes after invitro maturation. In all women combined, ZFP423 protein expression negatively correlated with fasting plasma glucose levels whereas the lipid content of newly formed adipocytes positively correlated with both PPARγ gene expression and serum free testosterone levels. In normal-weight women with PCOS compared with the control group, exaggerated SC abdominal ASC commitment to preadipocytes and enhanced adipocyte lipid content during maturation invitro negatively and positively correlate with circulating fasting glucose and androgen levels, respectively, as a possible mechanism to maintain glucose-insulin homeostasis when fat accretion is accelerated.

Diffuse parenchymal pulmonary amyloidosis associated with multiple myeloma: a case report and systematic review of the literature

BackgroundPulmonary is an uncommon site of extramedullary involvement in multiple myeloma (MM). Diffuse parenchymal amyloidosis as pulmonary manifestation of MM is even rarer. We report a rare case of diffuse parenchymal pulmonary amyloidosis associated with MM diagnosed by video-assisted thoracoscopic lung biopsy (VATLB).Case presentationA 58-year-old woman complained of cough and shortness of breath. HRCT disclosed diffuse ground-glass opacifications with interlobular septal thickening in bilateral lungs. A lung-biopsy sample obtained by VATLB revealed Congo Red-positive amorphous eosinophilic deposits in the alveolar septa. Surgical biopsy of abdominal wall skin and subcutaneous fat was also performed, which showed the apple-green birefringence with polarized light on Congo red stain was demonstrated in dermis. The serum immunoelectrophoresis showed monoclonal lambda light chains. A bone marrow biopsy specimen comprised 11.5% plasma cells. She was therefore diagnosed with diffuse parenchymal pulmonary amyloidosis accompanied by MM. The patient was referred to the hematology department for further chemotherapy.ConclusionsIt is important to recognize diffuse parenchymal pulmonary amyloidosis to avoid misdiagnosis.

Abstract P031: Effect of Exercise on Function and Differentiation of Adipose Tissue Derived Mesenchymal Stromal Cells (MSCs)

Approximately 422 million people have diabetes worldwide (2014) and it is predicted that diabetes will rise by nearly 54% by 2030. Aerobic exercise is known to show positive effect on health of diabetic and pre diabetic patients. The effect of exercise has been studied extensively using plasma biochemistry but cellular data is scares. Previously, we have shown endothelial progenitor cells (EPCs) can act as a strong cellular biomarker of endothelial function following aerobic exercise as an intervention. In this study, we are examining the effect of aerobic exercise on adipocyte derived MSCs to study stromal cell differentiation and as a cellular surrogate of fat metabolism. Methods: Overweight and obese subjects (n=5) were enrolled in a 12 week exercise intervention study. The biweekly exercise sessions were supervised by a trained exercise physiologist and consisted of a 1 hour sessions that included warm-up and cool-down and 30 min of combined aerobic and resistance training at an exercise intensity of 50-80% of heart rate reserve. Physical and biochemical parameters were tested pre and post exercise. Subcutaneous abdominal fat biopsies were obtained and fat derived stromal cells were cultured in vitro for 2-3 weeks. MSCs were analyzed for mRNA gene expression (qRT-PCR) and cellular oxygen consumption rate (OCR), pre and post 12 week exercise. Results: With exercise, A1C reduced significantly. An increase of METs was also noticed post exercise. Both basal and maximal respiration increased significantly post exercise when compared with commercially obtained MSCs. Simultaneously, mitochondrial genes COX4 and ATP5B (p= 0.01, 1.4 fold, 0.02, 1.5 fold respectively), Glucose transporter, GLUT1 (p=0.04, 1.8 fold), antioxidants GPX3 and CAT (p= 0.01, 3.2 fold and p=0.04, 1.5 fold respectively) upregulated whereas pro-inflammatory cyclo-oxygenase-2 (p=0.04, 2.5 fold) gene reduced significantly, post exercise. Regarding differentiation potential of multipotent MSCs, post exercise, we noted enhanced expression of bone markers such Alkaline Phosphatase (p= 0.03, 2.7 fold) BGLAP and RUNX2 (1.3 and 1.2 fold) and also for collagen marker COL2 (2.4 fold) expression. For adipogenic differentiation potential PPARG mRNA expression was reduced. Interestingly, serum value of osteocalcin increased significantly from 15.0 (5.5) to 16.3(6.1) ng/ml (9% increase, p=0.03) with 1% increase in bone alkaline phosphatase level, post exercise. Conclusion: We conclude that exercise augments cellular glucose transporters (GLUT1), anti-oxidants and reduce MSC inflammation and up-regulates mitochondrial function and gene expression profile of MSCs. Increased serum value of osteocalcin complement increased gene expression of bone formation markers indicating a cross talk between fat derived MSCs and bone formation, post exercise.