Search

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.

The mechanical characterization of adipose tissues is important for various medical purposes, including plastic surgery and biomechanical applications, such as computational human body models for the simulation of surgical procedures or injury prediction, for example, in the evaluation of vehicle crashworthiness. In this context, the measurement of human subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) mechanical properties in relation to subject characteristics may be really relevant. The aim of this work was to properly characterize the mechanical response of adipose tissues in patients with obesity. Then, the data were exploited to develop a reliable finite element model of the adipose tissues characterized by a constitutive material model that accounted for nonlinear elasticity and time dependence. Mechanical tests have been performed on both SAT and VAT specimens, which have been harvested from patients with severe obesity during standard laparoscopic sleeve gastrectomy intervention. The experimental campaign included indentation tests, which permitted us to obtain the initial/final indentation stiffnesses for each specimen. Statistical results revealed a higher statistical stiffness in SAT than in VAT, with an initial/final indentation stiffness of 1.65 (SD ± 0.29) N/30.30 (SD ± 20) N compared to 1.29 (SD ± 0.30) N/21.00 (SD ± 16) N. Moreover, the results showed that gender, BMI, and age did not significantly affect the stiffness. The experimental results were used in the identification of the constitutive parameters to be inserted in the constitutive material model. Such constitutive characterization of VAT and SAT mechanics can be the starting point for the future development of more accurate computational models of the human adipose tissue and, in general, of the human body for the optimization of numerous medical and biomechanical procedures and applications.

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.

Systemic diseases affect multiple tissues that interact with each other within a network difficult to explore at the body level. However, understanding the interdependences between tissues could be of high relevance for drug target identification, especially at the first stages of disease development. In vitro systems have the advantages of accessibility to measurements and precise controllability of culture conditions, but currently have limitations in mimicking human in vivo systemic tissue response. In this work, we present an in vitro model of cross-talk between an ex vivo culture of adipose tissue from an obese donor and a skeletal muscle in vitro model from a healthy donor. This is relevant to understand type 2 diabetes mellitus pathogenesis, as obesity is one of its main risk factors. The human adipose tissue biopsy was maintained as a three-dimensional culture for 48h. Its conditioned culture medium was used to stimulate a human skeletal muscle-on-chip, developed by differentiating primary cells of a patient's biopsy under topological cues and molecular self-regulation. This system has been characterized to demonstrate its ability to mimic important features of the normal skeletal muscle response in vivo. We then found that the conditioned medium from a diseased adipose tissue is able to perturb the normal insulin sensitivity of a healthy skeletal muscle, as reported in the early stages of diabetes onset. In perspective, this work represents an important step toward the development of technological platforms that allow to study and dissect the systemic interaction between unhealthy and healthy tissues in vitro. (c) 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2766, 2019.

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.

Pre-operative diet may play an important role as far as patients’ fitness for surgery, post-operative outcomes, and successful weight loss. Our aim was to compare surgical outcome and weight loss in two groups of patients who were offered two different pre-operative kinds of diet: very low calorie diet (VLCD) and very low calorie ketogenic diet (VLCKD). Patients candidate for bariatric surgery (laparoscopic sleeve gastrectomy) were registered and assessed according to pre- and post-diet BMI, operative time, hospital stay, drainage output, and hemoglobin (Hb) levels. Patients’ preference influenced the type of diet. From January to December 2016, 178 patients (139 F and 39 M) were enrolled in this study. The mean age was 43 years. In total, 72 patients were on VLCKD while 106 patients on VLCD. Pre-diet mean BMI was 46.3 ± 6.3 kg/m2 for VLCKD group and 43.1 ± 6.9 kg/m2 for VLCD group, while immediately pre-op BMI were 43.9 ± 5.9 kg/m2 and 41.9 ± 6.8 kg/m2, respectively. Drainage output and hemoglobin levels after surgery resulted significantly correlated with diet induced BMI reduction (141.2 ± 75.8 vs. 190.7 ± 183.6 ml, p = 0.032; 13.1 ± 1.2 vs. 12.7 ± 1.5 g/l, p = 0.04). The percentage of patients requiring a hospital stay longer than anticipated (> 3 days) was 2.8% in the VLCKD group and 10.4% in the VLCD group (p = 0.048). In our experience, VLCKD showed better results than VLCD on surgical outcome, influencing drainage output, post-operative hemoglobin levels, and hospital stay.

Oxygen radicals generated by p66Shc drive adipogenesis, but contradictory data exist on the role of p66Shc in the development of obesity and the metabolic syndrome. We herein explored the relationships among p66Shc, adipose tissue remodelling and glucose metabolism using mouse models and human adipose tissue samples.In wild-type (WT), leptin-deficient (ob/ob), p66Shc(-/-) and p66Shc(-/-) ob/ob mice up to 30 weeks of age, we analysed body weight, subcutaneous and visceral adipose tissue histopathology, glucose tolerance and insulin sensitivity, and liver and muscle fat accumulation. A group of mice on a high fat diet (HFD) was also analysed. A parallel study was conducted on adipose tissue collected from patients undergoing elective surgery.We found that p66Shc(-/-) mice were slightly leaner than WT mice, and p66Shc(-/-) ob/ob mice became less obese than ob/ob mice. Despite their lower body weight, p66Shc(-/-) mice accumulated ectopic fat in the liver and muscles, and were glucose intolerant and insulin resistant. Features of adverse adipose tissue remodelling induced by obesity, including adipocyte enlargement, apoptosis, inflammation and perfusion were modestly and transiently improved by p66Shc (also known as Shc1) deletion. After 12 weeks of the HFD, p66Shc(-/-) mice were leaner than but equally glucose intolerant and insulin resistant compared with WT mice. In 77 patients, we found a direct correlation between BMI and p66Shc protein levels. Patients with low p66Shc levels were less obese, but were not protected from other metabolic syndrome features (diabetes, dyslipidaemia and hypertension).In mice and humans, reduced p66Shc levels protect from obesity, but not from ectopic fat accumulation, glucose intolerance and insulin resistance.

Laparoscopic sleeve gastrectomy (LSG) is now considered an effective bariatric procedure (American Society for Metabolic and Bariatric Surgery statement). We attempted to assess the size of the gastric fundus remaining after LSG and gastric voiding rate (fast/slow) by radiological upper gastrointestinal series (UGS) with a water-soluble contrast medium (CM). The findings were compared with weight loss data. Seventy-four obese patients underwent LSG. Radiological UGS were used to measure the remaining fundus size in 28 of 74 patients 24–72 h after the procedure, with the aid of Matlab software and a library image processing toolbox (MathWorks®). Sleeve voiding was measured in 57 of 74 patients, based on the patients’ radiological reports. The mean volume of the remaining fundus was 17.56 ml (range 1.00–77.03 ml). The mean percent excess BMI loss (%EBL) was 39.5%, 53.7%, and 60.8%, respectively, 3, 6, and 12 months after LSG. Sleeve voiding was fast in 49 of 57 patients (85.96%) and slow in eight (14.03%). No correlation was found between the estimated volume of the remaining gastric fundus and weight loss (%EBL) after LSG. Patients showing a rapid gastroduodenal transit of the CM achieved a better weight loss than patients with a slow voiding rate.