The Neglected Role of Bile Duct Epithelial Cells in NASH.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and affects 25% of the population in Western countries. NAFLD is the hepatic manifestation of the metabolic syndrome, linked to insulin resistance, which is the common pathogenetic mechanism. In approximately 40% of NAFLD patients, steatosis is associated with necro-inflammation and fibrosis, resulting in nonalcoholic steatohepatitis (NASH), a severe condition that may progress to cirrhosis and liver cancer. Although the hepatocyte represents the main target of the disease, involvement of the bile ducts occurs in a subset of patients with NASH, and is characterized by ductular reaction and activation of the progenitor cell compartment, which incites portal fibrosis and disease progression. We aim to dissect the multiple biological effects that adipokines and metabolic alterations exert on cholangiocytes to derive novel information on the mechanisms driven by insulin resistance, which promote fibro-inflammation and carcinogenesis in NASH.

Acute pancreatitis due to severe hypertriglyceridemia in the COVID-19 era: The role of therapeutic plasma exchange.

The psychosocial consequences of the COVID-19 pandemic caused multifaceted challenges in clinical and therapeutic practices. This was the case at the Therapeutic Apheresis Unit of the Padua University Hospital too. Several published reports describe the increase in alcohol and food addiction diseases. In this context, during the last months, the Padua Therapeutic Apheresis Unit treated many more patients with acute pancreatitis due to severe hypertriglyceridemia with therapeutic plasma exchange than in the previous ten years. Furthermore, retrospective cohort studies have been recently published describing the onset of acute pancreatitis during the COVID-19 infection even if, to date, there is still insufficient evidence to estabilish a direct causality. Anyway, the COVID-19 pandemic translated into changes of the overall disease prevalence scenario and therefore the Padua Therapeutic Apheresis Unit will need to reorganise its Therapeutic Apheresis activity.

Association of obstructive sleep apnea with non-alcoholic fatty liver disease in patients with obesity: an observational study.

PURPOSE: Obstructive Sleep Apnea (OSA) is associated with the presence and severity of Non-Alcoholic Fatty Liver Disease (NAFLD). We aimed to investigate the relationship between the severity of OSA and NAFLD and to recognize a polysomnographic parameter correlated with progression of fibrosis, determined by a non-invasive score of liver fibrosis, FIBrosis-4 index (FIB-4), in patients affected by severe obesity and OSA. METHODS: We enrolled 334 patients (Body Mass Index, BMI 44.78 ± 8.99 kg/m2), divided into classes according to severity of OSA evaluated with Apnea Hypopnea Index (AHI): OSAS 0 or absent (17%), mild OSA (26%), moderate OSA (20%), severe OSAS (37%). We studied anthropometric, polysomnographic, biochemical data and FIB-4. A multiple regression model was computed to identify a polysomnographic independent predictor of FIB-4 among those parameters previously simple correlated with FIB-4. RESULTS: The severity of OSA was associated with a decrease in High-Density Lipoprotein-cholesterol (HDL) and an increase in BMI, triglycerides, Homeostasis model assessment insulin-resistance index (HOMA), transaminases and FIB-4. FIB-4 correlated with sex, age, BMI, AHI, mean percentage oxyhaemoglobin (meanSaO2%), number of desaturations, platelets, transaminases, HDL, triglycerides and HOMA. The only variables independently related to FIB-4 were sex, BMI, triglycerides and meanSpO2 (r = 0.47, AdjRsqr = 0.197). CONCLUSION: MeanSpO2% represented an independent determinant for the worsening of FIB-4 in patients with severe obesity and OSA. Hence, it could hypothesize a clinical role of meanSaO2% in recognizing patients with obesity and OSA and higher risk of developing advanced fibrosis and, thus, to undergo further investigation. LEVEL III: Evidence obtained from well-designed cohort analytic studies.

Correction to: Diet approach before and after bariatric surgery.

The original version of this article unfortunately, has the incorrect title reported in the published paper.

Diet approach before and after bariatric surgery.

Bariatric surgery (BS) is today the most effective therapy for inducing long-term weight loss and for reducing comorbidity burden and mortality in patients with severe obesity. On the other hand, BS may be associated to new clinical problems, complications and side effects, in particular in the nutritional domain. Therefore, the nutritional management of the bariatric patients requires specific nutritional skills. In this paper, a brief overview of the nutritional management of the bariatric patients will be provided from pre-operative to post-operative phase. Patients with severe obesity often display micronutrient deficiencies when compared to normal weight controls. Therefore, nutritional status should be checked in every patient and correction of deficiencies attempted before surgery. At present, evidences from randomized and retrospective studies do not support the hypothesis that pre-operative weight loss could improve weight loss after BS surgery, and the insurance-mandated policy of a preoperative weight loss as a pre-requisite for admission to surgery is not supported by medical evidence. On the contrary, some studies suggest that a modest weight loss of 5-10% in the immediate preoperative period could facilitate surgery and reduce the risk of complications. Very low calories diet (VLCD) and very low calories ketogenic diets (VLCKD) are the most frequently used methods for the induction of a pre-operative weight loss today. After surgery, nutritional counselling is recommended in order to facilitate the adaptation of the eating habits to the new gastro-intestinal physiology. Nutritional deficits may arise according to the type of bariatric procedure and they should be prevented, diagnosed and eventually treated. Finally, specific nutritional problems, like dumping syndrome and reactive hypoglycaemia, can occur and should be managed largely by nutritional manipulation. In conclusion, the nutritional management of the bariatric patients requires specific nutritional skills and the intervention of experienced nutritionists and dieticians.

Short-term effects of surgical weight loss after sleeve gastrectomy on sex steroids plasma levels and PSA concentration in men with severe obesity.

Male obesity is known to be associated with hypogonadism, which can be reverted after surgical weight reduction. However, the evidence about how rapidly this effect rises after surgery and what consequences each procedure have on prostate function and prostatic-specific antigen (PSA) concentration is scarce. So, we evaluated total testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone and PSA plasma levels in a group of 29 Caucasian obese men (BMI - 43.4 ± 8.5 kg/m2) before and one month after sleeve gastrectomy. 19 lean healthy male subjects were considered as controls. As expected, obese patients showed a high prevalence of hypogonadism (51.6%) at baseline, with reduced total testosterone compared to lean controls (10.8 ± 3.5 vs 15.7 ± 4.2 nmol/l, p < .01), higher estradiol (124.4 ± 46.5 vs 78.7 ± 39.6 pmol/l, p < .01), lower luteinizing hormone and follicle stimulating hormone (3.6 ± 1.3 and 2.5 ± 0.9 vs 5.2 ± 2.4 and 5.9 ± 3.8 U/L, respectively, p < .05) plasma levels. One month after surgery, patients showed a significant body weight reduction (-17.2 ± 6.7 kg) with increased total testosterone (from 10.8 ± 3.5 to 18.9 ± 4.9 nmol/l, p < .001), reduced estradiol (from 124.4 ± 46.5 to 96.1 ± 34.3 pmol/l, p < .05) and increased PSA (from 0.74 ± 0.38 to 1.0 ± 0.51 µg/l, p < .001). These results confirm that hypogonadism is highly prevalent in obese males, but they also show that it can be early reversed after sleeve gastrectomy, further confirming the strong indication to surgery of hypogonadal patients with severely reduced quality of life. Higher testosterone levels may be responsible for the increase of PSA observed after surgery; however, PSA concentration has to be monitored over time to avoid underrating of potential severe prostate diseases.

Exercise training boosts eNOS-dependent mitochondrial biogenesis in mouse heart: role in adaptation of glucose metabolism.

Endurance exercise training increases cardiac energy metabolism through poorly understood mechanisms. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) in cardiomyocytes contributes to cardiac adaptation. Here we demonstrate that the NO donor diethylenetriamine-NO (DETA-NO) activated mitochondrial biogenesis and function, as assessed by upregulated peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A (Tfam) expression, and by increased mitochondrial DNA content and citrate synthase activity in primary mouse cardiomyocytes. DETA-NO also induced mitochondrial biogenesis and function and enhanced both basal and insulin-stimulated glucose uptake in HL-1 cardiomyocytes. The DETA-NO-mediated effects were suppressed by either PGC-1α or Tfam small-interference RNA in HL-1 cardiomyocytes. Wild-type and eNOS(-/-) mice were subjected to 6 wk graduated swim training. We found that eNOS expression, mitochondrial biogenesis, mitochondrial volume density and number, and both basal and insulin-stimulated glucose uptake were increased in left ventricles of swim-trained wild-type mice. On the contrary, the genetic deletion of eNOS prevented all these adaptive phenomena. Our findings demonstrate that exercise training promotes eNOS-dependent mitochondrial biogenesis in heart, which behaves as an essential step in cardiac glucose transport.

Defective ADAMTS13 synthesis as a possible consequence of NASH in an obese patient with recurrent thrombotic thrombocytopenic purpura.

OBJECTIVES: Thrombotic thrombocytopenic purpura (TTP) is a rare and devastating hematologic disorder frequently associated with multiple organ failure and sometimes death. This syndrome is mainly associated with severe deficiency of ADAMTS13, a disintegrin and metalloprotease with thrombospondin (TSP)-1 repeats, cleaving high molecular weight von Willebrand Factor (ULVWF) multimers. Decreased plasma ADAMTS13 activity results in the accumulation of ULVWF multimers with consequent platelet activation. Recently, obesity has been considered as a potential independent risk factor for TTP, but the reason of this association is still unknown. METHODS AND RESULTS: We describe an unusual case of fatal recurrent TTP in a morbid obese female with non-alcoholic steatohepatitis (NASH) and severe ADAMTS13 activity deficiency due neither to an inhibitory autoantibody nor to a gene mutation. CONCLUSIONS: Visceral obesity is associated with non-alcoholic fatty liver disease (NAFLD) and NASH: we hypothesized that these conditions can influence ADAMTS13 antigen and activity. In fact, hepatic stellate cells (HSC) are the main producers of ADAMTS13, and a decrease in ADAMTS13 activity has been reported in liver disease.

Body Weight Reduction by Bariatric Surgery Reduces the Plasma Levels of the Novel Orexigenic Gut Hormone Insulin-like Peptide 5 in Patients with Severe Obesity.

Insulin-like factor 5 (INSL5), a novel hormone secreted by the enteroendocrine cells of the distal colon, has been implicated in appetite and body weight regulation in animals given its orexigenic properties. We investigated basal INSL5 plasma levels in a group of morbidly obese subjects before and after laparoscopic sleeve gastrectomy. Furthermore, we analyzed the expression of INSL5 in human adipose tissue. Before bariatric surgery, obese subjects showed basal INSL5 plasma levels that were positively correlated with BMI, fat mass, and leptin plasma levels. After weight loss by laparoscopic sleeve gastrectomy, INSL5 plasma levels in obese subjects were significantly lower than those observed before surgery. Finally, we did not detect any expression of the INSL5 gene in human adipose tissue, both at the mRNA and protein levels. The present data show that subjects with obesity have INSL5 plasma levels positively correlating with adiposity markers. After bariatric surgery, INSL5 plasma levels decreased significantly, and this decrease was not directly due to the loss of adipose tissue since this tissue does not express INSL5. Considering the orexigenic properties of INSL5, the reduction of its plasma levels after bariatric surgery in obese subjects could participate in the still unclear mechanisms leading to appetite reduction that characterize bariatric surgery procedures.

Presence of anti-ADAMTS13 antibodies in obesity.

BACKGROUND: The low-grade chronic inflammation present in obesity has been recognized as a risk factor for thrombosis, atherosclerosis and cardiovascular complications. In this context, production by adipose organ of a number of inflammatory adipokines could play a crucial role. It has been reported that obesity represents a risk factor for acquired thrombotic thrombocytopenic purpura (TTP), a disease caused by ADAMTS13 deficiency because of anti-ADAMTS13 antibodies, but the pathophysiological link between obesity and TTP is still unknown. We aimed to investigate mechanisms linking obesity to risk of TTP. MATERIALS AND METHODS: Eighty obese patients consecutively admitted to Bariatric Unit of Padua between 2006 and 2009, and 39 lean subjects were characterized by anthropometric, metabolic and inflammatory parameters. ADAMTS13 autoantibodies, activity and antigen levels, and several cytokines including thrombospondin-1 were measured. RESULTS: 21.3% of obese patients were positive for noninhibitory ADAMTS13 autoantibodies, while all lean subjects were negative (P<0.01). No differences in ADAMTS13 activity and antigen levels were found. Thrombospondin-1 levels were significantly higher in obese than in lean subjects (974.4 ± 592.7 vs. 318.9 ± 202.1 ng/mL; P<0.001) and were inversely correlated with ADAMTS13 activity (R=-0.4853; P<0.001). Dot blot suggests that anti-ADAMTS13 antibodies in obese patients bind recombinant thrombospondin-1. CONCLUSIONS: We suggest that anti-ADAMTS13 antibodies are directed against thrombospondin domains shared between ADAMTS13 and thrombospondin-1 and that their generation may be sustained by high levels of thrombospondin-1. This phenomenon could be of relevance, because little is known on the pathogenesis of TTP and its possible link with obesity.

Metabolic Slowing Vanished 5 Years After Sleeve Gastrectomy in Patients With Obesity and Prediabetes/Diabetes.

BACKGROUND: Resting energy expenditure (REE) decreases after weight loss more than expected according to body composition changes. Metabolic adaptation (MA) or metabolic slowing represents the difference between measured (m) and predicted (p) REE, and it is not clear whether it persists in the long-term. The aim of this study is to evaluate MA occurring 1 year (V1) and 5 years (V5) after laparoscopic sleeve gastrectomy (LSG) in patients with obesity and normal glucose tolerance, prediabetes (preDM) and type 2 diabetes (T2DM). METHODS: We reassessed 37 patients (14 males/23 females) of 44.8 ±â€…10 years old, since they registered all the biochemical, body composition, and REE assessments at baseline (V0), V1, and V5. Physical activity (PA) was assessed by interview and questionnaire. RESULTS: Patients displayed a percentage of weight loss of 31.5 ±â€…7.4% at V1 and a weight regain of 8.9 ±â€…7.5% at V5. Comparing V1 and V5, fat mass showed a slight increase (P = 0.011), while free fat mass remained unchanged (P = 0.304). PA improved at V1 (P < 0.001), remaining stable at V5 (P = 0.9). Measured REE (mREE) displayed a 31.2% reduction with a corresponding decrease of predicted REE (pREE) of 21.4% at V1, compared with V0 (P = 0.005), confirming a significant MA at V1. Conversely, no difference between mREE and pREE was observed at V5 (P = 0.112). CONCLUSION: Our results suggested that only patients with preDM and T2DM displayed MA at V1, which vanished 5 years after LSG. Patients who practiced more PA prevent MA after surgery-induced wight loss.

Oral Manifestations and Maxillo-Facial Features in the Acromegalic Patient: A Literature Review.

Background: Acromegaly is a chronic disease caused by an abnormal secretion of growth hormone (GH) by a pituitary adenoma, resulting in an increased circulating concentration of insulin-like growth factor 1 (IGF-1). The main characteristics are a slow progression of signs and symptoms, with multisystemic involvement, leading to acral overgrowth, progressive somatic changes, and a complex range of comorbidities. Most of these comorbidities can be controlled with treatment. The literature reveals that the most evident and early signs are those related to soft tissue thickening and skeletal growth, especially in the head and neck region. Methods: The authors reviewed the available literature on the clinical oro-dental features of acromegaly, selecting articles from PubMed and Google Scholar. The aim of this review was to summarize all the reported clinical oro-dental features of acromegalic patients. Results: The most common facial dimorphisms involved the maxillo-facial district, with hypertrophy of the paranasal sinuses, thickening of the frontal bones, and protruding glabella, which may be associated with joint pain and clicks. Regarding the oro-dental signs, the most frequent are dental diastema (40-43%), mandibular overgrowth (22-24%), mandibular prognathism (20-22%), and macroglossia (54-58%). These signs of acromegaly can be significantly reduced with adequate treatment, which is more effective when initiated early. Conclusions: Increased awareness of acromegaly among dentists and maxillo-facial surgeons, along with the early identification of oro-facial changes, could lead to an earlier diagnosis and treatment, thereby improving patients' quality of life and prognosis.

Higher Levels of C-Reactive Protein and Ferritin in Patients with Overweight and Obesity and SARS-CoV-2-Related Pneumonia.

INTRODUCTION: Overweight and obesity are associated with a more severe COronaVirus Disease 19 (COVID-19). Adipose tissue-related chronic inflammation could be a promoter for the occurrence of the cytokine storm that predicts aggravation of COVID-19. The primary aim was to investigate if this increased risk for more severe COVID-19 was associated with a higher inflammatory response. METHODS: We enrolled patients <75 years old hospitalized in a medical COVID-19 ward with SARS-CoV-2-related pneumonia. Patients were classified according to BMI as normal weight, overweight, and obesity. Laboratory parameters were measured at admission and every second day during the hospital stay. RESULTS: Ninety patients (64.4% males; median age 61 years) were enrolled. Invasive mechanical ventilation (IMV) was needed in 9% of the patients with normal weight, in 32.4% of the patients with overweight, and in 12.9% of the patients with obesity (p = 0.045). Maximal C-reactive protein (CRP) level during hospital stay was 92 (48-122) mg/L in patients with normal weight, 140 (82-265) mg/L in patients with overweight, and 117 (67-160) mg/L in patients with obesity (p = 0.037). Maximal ferritin values were 564 (403-1,379) µg/L in patients with a normal weight, 1,253 (754-2,532) µg/L in patients with overweight, and 828 (279-1,582) µg/L in patients with obesity (p = 0.015). CONCLUSION: Patients with overweight and obesity required more IMV and had higher peaks of CRP and ferritin than patients with normal weight during COVID-19.

Improvement of Lipid Profile after One-Anastomosis Gastric Bypass Compared to Sleeve Gastrectomy.

Fewer studies compared the improvement of plasma lipid levels after different types of surgery, in particular compared to one-anastomosis gastric bypass (OAGB). The aim of our study was to investigate how laparoscopic sleeve gastrectomy (LSG) and OAGB impact on weight loss and lipid profile 18 months after surgery, in patients with severe obesity. Forty-six patients treated with OAGB were matched to eighty-eight patients submitted to LSG. Weight loss after OAGB (33.2%) was more evident than after LSG (29.6%) (p = 0.024). The difference in the prevalence of dyslipidemia showed a statistically significant reduction only after OAGB (61% versus 22%, p < 0.001). After adjustment for delta body mass index (BMI), age and sex, we demonstrated a statistically significant decrease of the differences between the changes before and after (delta Δ) the two surgery procedures: Δ total cholesterol values (p < 0.001), Δ low density lipoprotein-cholesterol values (p < 0.001) and Δ triglycerides values (p = 0.007). Patients with severe obesity undergoing to OAGB presented a better improvement of lipid plasma values than LSG patients. The reduction of lipid plasma levels was independent of the significant decrease of BMI after surgery, of age and of sex.

Liver histopathology in COVID-19 patients: A mono-Institutional series of liver biopsies and autopsy specimens.

Few studies have focused on COVID-19 patients' hepatic histopathological features. Many of the described morphological landscapes are non-specific and possibly due to other comorbidities or to Sars-CoV-2-related therapies. We describe the hepatic histopathological findings of 3 liver biopsies obtained from living COVID-19 patients in which active SARS-CoV-2 infection was molecularly confirmed and biopsied because of significant alterations of liver function tests and 25 livers analyzed during COVID-19-related autopsies. Main histopathological findings were (i) the absence of significant biliary tree or vascular damages, (ii) mild/absent lymphocytic hepatitis; (iii) activation of (pigmented) Kupffer cells, (iv) hepatocellular regenerative changes, (v) the presence of steatosis, (vi) sinusoidal ectasia, micro-thrombosis and acinar atrophy in autopsy specimens No viral particle actively infecting the hepatic or endothelial cells was detected at in situ hybridization. The morphological features observed within the hepatic parenchyma are not specific and should be considered as the result of an indirect insult resulting from the viral infection or the adopted therapeutic protocols.

Obesity and COVID-19: An Italian Snapshot.

OBJECTIVE: The clinical manifestations of coronavirus disease (COVID-19) run from asymptomatic disease to severe acute respiratory syndrome. Older age and comorbidities are associated to more severe disease. A role of obesity is suspected. METHODS: Patients hospitalized in the medical COVID-19 ward with severe acute respiratory syndrome coronavirus 2-related pneumonia were enrolled. The primary outcome of the study was to assess the relationship between the severity of COVID-19 and obesity classes according to BMI. RESULTS: A total of 92 patients (61.9% males; age 70.5 [13.3] years) were enrolled. Patients with overweight and obesity were younger than patients with normal weight (68.0 [12.6] and 67.0 [12.6] years vs. 76.1 [13.0] years, P < 0.01). A higher need for assisted ventilation beyond pure oxygen support (invasive mechanical ventilation or noninvasive ventilation) and a higher admission to intensive or semi-intensive care units were observed in patients with overweight and obesity (P < 0.01 and P < 0.05, respectively) even after adjusting for sex, age, and comorbidities (P < 0.05 and P < 0.001, respectively) or when patients with dementia or advanced cancer were removed from the analysis (P < 0.05). CONCLUSIONS: Patients with overweight and obesity admitted in a medical ward for severe acute respiratory syndrome coronavirus 2-related pneumonia, despite their younger age, required more frequently assisted ventilation and access to intensive or semi-intensive care units than normal weight patients.

Resting Energy Expenditure, Insulin Resistance and UCP1 Expression in Human Subcutaneous and Visceral Adipose Tissue of Patients With Obesity.

Determinants of resting energy expenditure (REE) in humans are still under investigation, especially the association with insulin resistance. Brown adipose tissue (AT) regulates energy expenditure through the activity of the uncoupling protein 1 (UCP1). White AT browning is the process by which some adipocytes within AT depots acquire properties of brown adipocytes ("brite" adipocytes) and it correlates with metabolic improvement. We analyzed determinants of REE in patients with obesity and assessed UCP1 expression as a "brite" marker in abdominal subcutaneous AT (SAT) and visceral omental AT (VAT). Clinical data, REE, free fat mass (FFM), and fat mass (FM) were determined in 209 patients with obesity. UCP1, PPARG coactivator 1 alpha (PPARGC1A), transcription factor A, mitochondrial (TFAM), T-box transcription factor 1 (TBX1), and solute carrier family 27 member 1 (SLC27A1) expression was assayed in SAT and VAT samples, obtained during sleeve gastrectomy from 62 patients with obesity. REE and body composition data were also available for a subgroup of 35 of whom. In 209 patients with obesity a multiple regression model was computed with REE as the dependent variable and sex, waist, FFM, FM, homeostasis model assessment-insulin resistance (HOMA), interleukin-6 and High Density Lipoprotein-cholesterol as the independent variables. Only FFM, FM and HOMA were independently correlated with REE (r = 0.787, AdjRsqr = 0.602). In each patient VAT displayed a higher UCP1, PPARGC1A, TFAM, TBX1, and SLC27A1 expression than SAT and UCP1 expression in VAT (UCP1-VAT) correlated with Body Mass Index (BMI) (r = 0.287, p < 0.05). Introducing UCP1-VAT in the multivariate model, we showed that FFM, HOMA, interleukin-6, High Density Lipoprotein-cholesterol, and UCP1-VAT were independent factors correlated with REE (r = 0.736, AdjRsqr = 0.612). We confirmed that REE correlates with FFM, FM and HOMA in a large cohort of patients. Our results clearly showed that UCP1-VAT expression was significantly increased in severe human obesity (BMI > 50 kg/m2) and that it behaved as an independent predictor of REE. Lastly, we suggest that an increased REE and browning in metabolically complicated severe obesity could represent an effort to counteract further weight gain.

SCCA-IgM as a Potential Biomarker of Non-Alcoholic Fatty Liver Disease in Patients with Obesity, Prediabetes and Diabetes Undergoing Sleeve Gastrectomy.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in obesity and its presence should be screened. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for obesity, but its effects on NAFLD are still to be firmly established. The diagnosis of non-alcoholic steatohepatitis (NASH) is currently performed by liver biopsy, a costly and invasive procedure. Squamous cell carcinoma antigen-IgM (SCCA-IgM) is a biomarker of viral hepatitis to hepatocellular carcinoma development and its role in NAFLD to NASH progression has not yet been investigated. OBJECTIVE: The aim of this study was to evaluate SCCA-IgM as a non-invasive biomarker of NAFLD/NASH in patients with different degrees of metabolic-complicated obesity before and after LSG. METHOD: Fifty-six patients with obesity were studied before and 12 months after LSG; anthropometric, biochemical, clinical, and imaging data were collected. RESULTS: At baseline steatosis was strongly associated with the glycaemic profile (p = 0.016) and was already present in prediabetic patients with obesity (82%). Only 3 patients had an SCCA-IgM level above the normal cut-off. SCCA-IgM titre did not change according to glycaemic profile or steatosis. Metabolic and inflammatory factors and transaminases significantly reduced after LSG-induced weight loss, except for SCCA-IgM. The ALT/AST ratio decreased post-LSG correlated with BMI (r = 0.297, p = 0.031), insulin (r = 0.354, p = 0.014), and triglycerides (r = 0.355, p = 0.009) reduction. CONCLUSIONS: Our results confirm the tight link between NAFLD and metabolic complications, suggesting prediabetes as a new risk factor of steatosis. SCCA-IgM does not seem to have a role in the identification and prognosis of NAFLD.

Characterization of subcutaneous and omental adipose tissue in patients with obesity and with different degrees of glucose impairment.

Although obesity represents a risk factor for the development of type 2 diabetes mellitus (T2DM), the link between these pathological conditions is not so clear. The manner in which the different elements of adipose tissue (AT) interplay in order to grow has been suggested to have a role in the genesis of metabolic complications, but this has not yet been fully addressed in humans. Through IHC, transmission electron microscopy, cytometry, and in vitro cultures, we described the morphological and functional changes of subcutaneous and visceral AT (SAT and VAT) in normoglycemic, prediabetic and T2DM patients with obesity compared to lean subjects. In both SAT and VAT we measured a hypertrophic and hyperplastic expansion, causing similar vascular rarefaction in obese patients with different degrees of metabolic complications. Capillaries display dysfunctional basement membrane thickening only in T2DM patients evidencing VAT as a new target of T2DM microangiopathy. The largest increase in adipocyte size and decrease in adipose stem cell number and adipogenic potential occur both in T2DM and in prediabetes. We showed that SAT and VAT remodeling with stemness deficit is associated with early glucose metabolism impairment suggesting the benefit of an AT-target therapy controlling hypertrophy and hyperplasia already in prediabetic obese patients.

Modifications of Resting Energy Expenditure After Sleeve Gastrectomy.

OBJECTIVES: Resting energy expenditure (REE) declines more than what is expected according to body composition changes after caloric restriction. This metabolic adaptation is considered one of the factors favoring weight regain. The aim of this study is to evaluate the changes of REE and calculate the degree of metabolic adaptation occurring after laparoscopic sleeve gastrectomy (LSG). METHODS: REE (by indirect calorimetry) and body composition (fat-free mass or FFM, fat mass or FM by bioelectrical impedance analysis) were determined before and after 12 months in 154 patients with obesity treated with laparoscopic sleeve gastrectomy (LSG). RESULTS: Weight loss was 29.8 ± 10.6%, with corresponding relative reductions in FM (44.5 ± 22.8%), FFM (13.7 ± 9.9%), and REE (27.3 ± 12.9%). A predictive equation for REE was computed by using the baseline FFM and FM values to account for body composition changes. A predicted post-weight loss REE was calculated by using this equation and entering post-weight loss body composition values. Observed post-surgery REE was significantly lower than predicted one (1410 ± 312 vs 1611 ± 340 kcal/day, P < 0.001) and metabolic adaptation, calculated as the difference between observed and predicted post-weight loss REE, was - 199 ± 238 kcal/day. The post-surgery level of metabolic adaptation was inversely related to postoperative percent weight loss (r = - 0.170; P < 0.05) and FM loss (r = - 0.245; P < 0.01). CONCLUSIONS: A significant reduction of resting energy expenditure and a significant degree of metabolic adaptation both occur after sleeve gastrectomy. A greater metabolic adaptation could be partly responsible for a lower weight loss after surgery.