Mast cells in human adipose tissue: link with morbid obesity, inflammatory status, and diabetes.

AIMS AND HYPOTHESIS: Mast cells are immune cells known for their role in several inflammatory and fibrotic diseases. Recent works in mice suggest that mast cells could be cellular actors involved in the pathophysiology of obesity, a disease characterized by white adipose tissue (WAT) and systemic inflammation. The aim of the study was to better characterize mast cells in WAT of obese with or without type 2 diabetes and lean subjects as well as to explore the relationship with WAT inflammation and fibrosis. METHODS: Subcutaneous and omental adipose tissue from six lean subjects, 10 obese nondiabetic, and 10 diabetic patients was analyzed by immunohistochemistry and real-time PCR for inflammatory and fibrosis markers. Cytokines secretion of mast cells isolated from WAT and cultured in different conditions was estimated by cytokine array kit. RESULTS: We found that mast cells are activated in human adipose tissue and localized preferentially in fibrosis depots, a local condition that stimulates their inflammatory state. Mast cells with tryptase(+) chymase(+) staining tended to be higher in obese omental adipose tissue. We found positive links between mast cell number and several characteristics of obese WAT including fibrosis, macrophage accumulation, and endothelial cell inflammation. Mast cell number and their inflammatory phenotype are associated with diabetes parameters. CONCLUSION AND INTERPRETATION: Mast cells are cellular actors of WAT inflammation and possibly fibrotic state found in obesity and diabetes. Whether mast cells could be involved in the pathophysiology of diabetes needs additional study as well as the positioning of these cells in driving pathological alterations of WAT in these chronic metabolic diseases.

Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss.

OBJECTIVE: Fibrosis is a newly appreciated hallmark of the pathological alteration of human white adipose tissue (WAT). We investigated the composition of subcutaneous (scWAT) and omental WAT (oWAT) fibrosis in obesity and its relationship with metabolic alterations and surgery-induced weight loss. RESEARCH DESIGN AND METHODS: Surgical biopsies for scWAT and oWAT were obtained in 65 obese (BMI 48.2 ± 0.8 kg/m(2)) and 9 lean subjects (BMI 22.8 ± 0.7 kg/m(2)). Obese subjects who were candidates for bariatric surgery were clinically characterized before, 3, 6, and 12 months after surgery, including fat mass evaluation by dual energy X-ray absorptiometry. WAT fibrosis was quantified and characterized using quantitative PCR, microscopic observation, and immunohistochemistry. RESULTS: Fibrosis amount, distribution and collagen types (I, III, and VI) present distinct characteristics in lean and obese subjects and with WAT depots localization (subcutaneous or omental). Obese subjects had more total fibrosis in oWAT and had more pericellular fibrosis around adipocytes than lean subjects in both depots. Macrophages and mastocytes were highly represented in fibrotic bundles in oWAT, whereas scWAT was more frequently characterized by hypocellular fibrosis. The oWAT fibrosis negatively correlated with omental adipocyte diameters (R = -0.30, P = 0.02), and with triglyceride levels (R = -0.42, P < 0.01), and positively with apoA1 (R = 0.25, P = 0.05). Importantly, scWAT fibrosis correlated negatively with fat mass loss measured at the three time points after surgery. CONCLUSIONS: Our data suggest differential clinical consequences of fibrosis in human WAT. In oWAT, fibrosis could contribute to limit adipocyte hypertrophy and is associated with a better lipid profile, whereas scWAT fibrosis may hamper fat mass loss induced by surgery.

[Bariatric surgery: surgical techniques and their complications]. / Chirurgie bariatrique: techniques chirurgicales et leurs complications.

Bariatric surgery is the only treatment permitting significant and long lasting results for patients suffering from morbid obesity. Indications are BMI>40 kg/m(2) or BMI >35 kg/m(2) associated with one or multiples comorbidities. In all cases, a multidisciplinary approach is required. Laparoscopic surgery because of its mini-invasive nature is a significant improvement for early and late postoperative courses. Adjustable gastric banding, gastric by-pass, sleeve gastrectomy, bilio-pancreatic diversions are in this order the most frequent bariatric procedures performed in France. Severe and early surgical complications are dominated by occlusions and anastomotic leakages. Late complications are dominated by small bowel occlusions. Early medical complications are thrombo-embolism manifestations. Late medical complications are vitamin and trace elements deficiencies. Severe complications are due to pauci-symptomaticity of patients and their poor clinical status. Every practitioner taking care of these patients have to know all principles, specificity and complications of this kind of surgery.

Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss.

CONTEXT: Macrophages accumulate in adipose tissue and possibly participate in metabolic complications in obesity. Macrophage number varies with adipose tissue site and weight loss, but whether this is accompanied by phenotypic changes is unknown. OBJECTIVE: The objective of the study was to characterize the activation state of adipose tissue macrophages in human obesity. DESIGN/SETTING: We performed a single-center prospective study. PARTICIPANTS/INTERVENTIONS: Paired biopsies of sc and omental adipose tissue were obtained during gastric surgery in 16 premenopausal obese women (aged 41.1 +/- 8.6 yr; body mass index 43.8 +/- 3.4 kg/m(2)). Subcutaneous adipose tissue biopsies were obtained 3 months later in obese subjects and in 10 nonobese women (aged 43.3 +/- 3.5 yr; body mass index 22.5 +/- 0.75 kg/m(2)). The number of macrophages stained with CD40, CD206, and CD163 surface markers was determined by immunochemistry. MAIN OUTCOMES: The number of CD40(+) macrophages significantly increased with obesity and in omental vs. sc adipose tissue in obese women. No significant changes in CD163(+) and CD206(+) macrophage counts was found with obesity and fat pad anatomical location. Three months after gastric surgery, the ratio of CD40(+) to CD206(+) macrophages was 2-fold lower than before surgery in the sc adipose tissue of obese subjects (P < 0.001) due to a concomitant decrease of CD40(+) and increase of CD206(+) macrophages counts. CONCLUSION: We suggest that the activation state of adipose tissue macrophages is weighted toward M1 over M2 status in obese subjects and switch to a less proinflammatory profile 3 months after gastric bypass.

Value of a systematic operative protocol for cocaine body packers.

BACKGROUND: Internal concealment of illicit drugs during international drug traffic represents an important problem in developed countries. These drug traffickers are called "body packers." The aim of this study was to analyze retroprospectively the surgical indications and complications for cocaine body packers and to describe our systematic operative protocol. METHODS: From January 1997 to December 2005, 1,181 cocaine body packers were admitted to our Medico-Judiciary Emergency Department. All patients had the same medical surveillance protocol. Nineteen patients required surgical procedure to remove drug packets. RESULTS: Thirteen patients had obstruction or intestinal retention (68%). Suspicion of packet rupture or cocaine intoxication occurred in six patients (32%). Zero to three enterotomies were necessary during laparotomy. No deaths occurred. One pouch abscess required relaparotomy and one wound abscess was treated medically. The median hospital stay was 7 days (range: 5-30 days). CONCLUSIONS: Few cocaine body packers required a laparotomy. Our systematic operative protocol allowed intestinal clearance and caused acceptable morbidity rate.