Lack of Adipocyte-Fndc5/Irisin Expression and Secretion Reduces Thermogenesis and Enhances Adipogenesis.

Irisin is a browning-stimulating molecule secreted from the fibronectin type III domain containing 5 precursor (FNDC5) by muscle tissue upon exercise stimulation. Despite its beneficial role, there is an unmet and clamorous need to discern many essential aspects of this protein and its mechanism of action not only as a myokine but also as an adipokine. Here we contribute to address this topic by revealing the nature and role of FNDC5/irisin in adipose tissue. First, we show that FNDC5/irisin expression and secretion are induced by adipocyte differentiation and confirm its over-secretion by human obese visceral (VAT) and subcutaneous (SAT) adipose tissues. Second, we show how secreted factors from human obese VAT and SAT decrease PGC1α, FNDC5 and UCP1 gene expression on differentiating adipocytes; this effect over UCP1 is blunted by blocking irisin in obese secretomes. Finally, by stable gene silencing FNDC5 we reveal that FNDC5-KO adipocytes show reduced UCP1 expression and enhanced adipogenesis.

Plasma FGF21 levels in obese patients undergoing energy-restricted diets or bariatric surgery: a marker of metabolic stress?

BACKGROUND: Fibroblast growth factor 21 (FGF21) has been suggested to be an endocrine signal of nutritional status and an active regulator of metabolism. However, there is no agreement on the effect of weight-loss therapies on circulating levels of FGF21 in humans. OBJECTIVE: To assess FGF21 circulating levels in adiposity excess and after different weight-loss strategies prescribed in five different groups from four independent centers. SUBJECTS AND METHODS: Body composition, ketosis, insulin sensitivity and FGF21 were evaluated in 181 excess body weight and 14 normal-weight subjects. From the excess body weight patients, two independent groups (discovery cohort; n=20 and validation cohort; n=28) undertook a very low-calorie ketogenic (VLCK) diet, a third group followed a low-calorie (LC) diet (n=84) and other two groups underwent bariatric surgery (discovery cohort; n=24 and validation cohort; n=25). The follow-up was 4 to 6 or 12 months, respectively. RESULTS: FGF21 levels were higher in excess body weight patients than in normal-weight subjects. The energy-restriction therapy to lose weight induced a significant decrease, with respect to baseline, in circulating levels of FGF21 (VLCK: -62.5 pg ml-1 or -14.8 pg ml-1 and LC diet: -67.9 pg ml-1). There were no differences in FGF21 levels between both energy-restriction treatments. On the contrary, after bariatric surgery morbidly obese patients showed a significant increase in FGF21, especially 1 month after surgery (148.8 pg ml-1 higher than baseline). The FGF21 differential changes occur concomitantly with a non-induced ketosis situation (0.66±0.56 mm) in bariatric surgery, and an improvement in adiposity and insulin sensitivity induced by the three therapies. CONCLUSIONS: FGF21 levels were reduced after energy-restricted treatments and severely increased after bariatric surgery, independently of the weight reduction magnitude, insulin sensitivity or ketosis. Therefore, FGF21 appears to be a marker of severe nutritional stress.

Parastomal hernia repair: laparoscopic ventral hernia meshplasty with stoma relocation. The current state and a clinical case presentation.

BACKGROUND: Parastomal hernia is a frequent complication after performing an ostomy, and although different technical options have been described, it lacks an ideal intervention to resolve it. The use of meshes and the laparoscopic approach, has led to a significant advance in resolving this condition. However, the ideal technique should guarantee must ensure integral repair of the abdominal wall, taking into account the functionality of the stoma. In large parastomal eventrations the repairing of the ventral hernia with a mesh and relocating the stoma in another quadrant may be an intervention that fulfills both principles, and open approach being described. METHODS: We review the current state of surgical management of this condition and analyze the different technical options. Present the first description for using a laparoscopic technique with meshplasty and stoma relocation in an obese patient with a complex parastomal hernia, with results in the 18 month follow up. CONCLUSIONS: Surgical technique repair of the parastomal hernia is sometimes a complex issue, which possibly requires different solutions according to the characteristics of the hernia and patient. The technique described of meshplasty with stoma relocation by laparoscopic approach has been revealed as an affordable technique, with minor inconvenience to the patient, absence of complications and good functional results in the long term, benefiting from the advantages of minimally invasive surgery itself.

Long-term results for liver transplantation from non-heart-beating donors maintained with chest and abdominal compression-decompression.

INTRODUCTION: The aim of this study was to evaluate long-term results after liver transplantation from non-heart-beating donors (NHBD) using the method of chest and abdominal compression-decompression to maintain donors. METHODS: From December 1995 to November 2004, 10 NHBD were identified and maintained by means of the method of chest and abdominal compression-decompression until family and judicial permission were granted. Nine donors were Maastricht type II and one was type IV. RESULTS: The mean age of donors was 40.5 years and the mean time under cardiopulmonary resuscitation (CPR) was 80 minutes. Orthotopic liver transplantation (OLT) was performed using these 10 liver grafts after a mean cold ischemia time of 561.5 minutes. All patients developed good posttransplant function, except for one patient who presented with primary nonfunction corrected with retransplantation. This complication was directly related to a long CPR time (P < .01). After a mean follow-up of 57 months, only one patient died from a hepatitis C virus (HCV) recurrence. The rest of the patients have maintained good graft function over time. CONCLUSIONS: NHBD maintained with the method of chest and abdominal compression-decompression are a valid choice to increase the donor pool. Liver transplantation using these grafts has proven good long-term results, comparable to their heart-beating counterparts.