bromochloroacetic-acid and Obesity

Hidradenitis suppurativa (HS) is an inflammatory, debilitating follicular skin disease with recurring flare-ups. The painful, deep-seated, inflamed lesions in the inverse areas of the body cause severe discomfort, and hence, serious psycho-social and economic costs. HS is common, but often misdiagnosed and mechanistically poorly understood. Furthermore, HS is notoriously difficult to treat resulting in a high unmet medical need. To provoke debate, rational experimentation and initiate strategic studies, we here present a concise viewpoint on seven topics: the diagnosis of HS, the role of mechanical friction, the critical importance of accurate clinical subgrouping, smoking and obesity, the role of bacteria, and our comprehensive view on HS pathogenesis with a central role for keratin clearance, and novel treatment approaches.

Topics: Diagnostic Errors; Friction; Hidradenitis Suppurativa; Humans; Immunologic Factors; Inflammation Mediators; Keratins; Metagenome; Models, Biological; Obesity; Risk Factors; Smoking; Stress, Mechanical; Sweat Glands

The relationship between resistin and non-alcoholic steatohepatitis (NASH) is not clear, some studies claimed that serum resistin levels were associated with neither the presence of NASH nor its severity, others declared that serum resistin was related with inflammation and fibrosis in NASH. Our animal study verified that the distribution of resistin in the liver is correlated with inflammation in NASH. However, there is no pertinent study in humans.. Thirty patients with NASH, 28 simple steatosis, and 43 controls were recruited. Blood was collected for resistin, liver chemistries, fasting insulin and some metabolic parameters. Liver histology was scored according to NAFLD activity scoring system. Hepatic resistin expression was examined by real-time polymerase chain reaction, immunohistochemistry. Resistin protein expression was confirmed by western blotting in 13 patients with concomitant NAFLD and gallstone.. Serum resistin was significantly elevated in both NASH and simple steatotic subjects compared with controls (all P < 0.05). Hepatic resistin was significantly increased in NASH patients in both mRNA and protein levels than those in simple steatosis and control subjects (all P < 0.05). Both serum and hepatic resistin had a correlation with obesity, but not with insulin resistance. The distribution of resistin positive cells was predominantly in perisinusoidal cells (such as Kupffer cells and hepatic stellate cells) in human NASH. Multivariate analysis revealed that waist-hip ratio, higher serum triglyceride, and hyperresistinemia were independent factors related to higher grade of steatosis; whereas hepatic resistin and serum cytokeratin predict NASH and severity of liver fibrosis.. Hepatic resistin overexpression in NASH patients is associated with the severity of liver inflammation and fibrosis. Liver-derived resistin may be involved in the pathogenesis of human NASH.

Topics: Adult; Case-Control Studies; Fatty Liver; Female; Hepatic Stellate Cells; Humans; Insulin Resistance; Keratins; Kupffer Cells; Liver Cirrhosis; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Prospective Studies; Resistin; RNA, Messenger; Triglycerides; Up-Regulation; Waist-Hip Ratio

Obesity causes changes in fatty acid metabolism that consequently leads to fatty liver. To identify the possible proteins involved in the processes of obesity, we performed a proteomic analysis of obesity-induced mouse liver. Male C57BL/6J mice that were fed a high-fat diet (HFD) for 24 wk, developed hepatic steatosis characterized by considerable increase in free fatty acid (FFA) and triglyceride levels. Body weights were measured weekly and other measurements at weeks 2, 6, 12, 16, and 24. 2-D-based proteomic analysis revealed that, compared with the normal diet (ND) (n=50), high-fat diet (n=50) changed the expression of 12 protein (8 up and 4 downregulated, by a 1.5× fold change and more, p<0.05). The most pronounced difference was observed in intermediate microfilament (IF) cytoskeleton proteins. In particular, vimentin (vim) as well as cytokeratins (CK-8 and CK-18) were significantly upregulated in obese animals. Moreover, the level of caspase-generated IF fragment was also positively correlated with the degree of steatosis. The results suggest a significant alteration in IF organization during the development of hepatic steatosis leading to inflammation. The expression profile of selected proteins including vim was validated by Western blot, microarray analysis, and hepatocyte morphology by immunohistochemistry. Our results suggest that vim, like CK-18, may be a useful marker for predicting obesity and liver disease.

Topics: Animals; Diet; Dietary Fats; Fatty Liver; Gene Expression Profiling; Hepatocytes; Humans; Intermediate Filaments; Keratins; Lipid Metabolism; Liver; Male; Mass Spectrometry; Mice; Mice, Inbred C57BL; Microarray Analysis; Obesity; Proteome; Proteomics; Random Allocation; Two-Dimensional Difference Gel Electrophoresis; Vimentin

Liver histology is the gold standard for diagnosis of non-alcoholic fatty liver disease. Ethical considerations and patient choice often preclude performing a liver biopsy, especially considering the rare but potential risk. Searching for a good serological marker substitute for the invasive procedure was the aim of our study. Keratins, mainly 8 and 18, play not only a mere structural role providing mechanical stability to hepatocytes, but also represent a target via toxic stress ultimately inducing apoptosis/necrosis. Tissue polypeptide-specific antigen (TPS), a serological mirror of keratin 18, is widely used as a marker for various cancers. This antigen was assessed in three different groups who were overweight or obese.. In this cross-sectional case-control study, 48 cancer-free patients with non-alcoholic steatohepatitis (NASH, Group 1), 48 patients with pure fatty liver (FL, Group 2), and 47 volunteers (Group 3) were studied. All of them were referred to our metabolic unit for routine evaluation.. The median (range) TPS levels were 123 (56-286) ng mL(-1) in NASH patients. FL patients and volunteers had significantly lower TPS levels, 76 (38-98) ng mL(-1) and 64 (28-87) ng mL(-1), respectively (P = 0.0001). A value of 88 ng mL(-1) in patients with underlying bright liver was associated with a high probability of NASH (sensitivity and specificity = 92% and 96%, respectively). One patient (2.1%) with FL had a TPS value > 88 ng mL(-1), but in the same group, 29 FL patients (60.4%) had an alanine aminotransferase value > 40 U L(-1). Based on a recent classification of liver fibrosis, the median (range) TPS values were significantly different among the stages: F1 (n = 23) = 100 (76-264) ng mL(-1); F2 (n = 21) = 134 (56-276) ng mL(-1); and F3 (n = 4) = 199.5 (123-286) ng mL(-1), respectively (P = 0.014).. Our study shows that TPS is a better marker than alanine aminotransferase activity, ultrasonography or the combination of both parameters in differentiating NASH from FL.

Topics: Adult; Alanine Transaminase; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Fatty Liver, Alcoholic; Female; Hepatitis; Humans; Keratins; Male; Obesity; Overweight; Peptides

The case of a 62-year-old woman with severe post-menopausal hirsutism is described. Her clinical history revealed regular menstrual periods until menopause at the age of 50, hysterectomy for fibromatosis at 58 years, non-insulin dependent diabetes mellitus, hypertension, obesity, severe hirsutism, which had developed in the previous 3 years, with a deeping of the voice. Examination showed android obesity, hypertension and severe hirsutism involving the face and the trunk. Endocrine evaluation pointed out regular adrenal function, serum total and free-testosterone in the adult male range, with normal androstenedione, DHEAS and 17OHP levels. Estradiol was slightly increased and LH and FSH were inappropriately low for her post-menopausal age. Computed tomography of the abdomen showed regular adrenal glands, and a radio-labeled cholesterol scan was negative. A further pelvic transvaginal ultrasonography revealed a small cystic formation near the right ovary and a slight increase in the size of the left ovary. The patient underwent bilateral ovariectomy. Histological examination showed a lipoid cell tumor within the left ovary. Immunohistochemical studies were positive for inhibin and cytokeratin. After surgery, serum testosterone fell to normal levels, gonadotropins increased to menopausal levels, confirming that the tumor was able to produce both LH, and FSH-inhibiting factors, and hirsutism greatly improved. Periodic hormonal tests remained normal and CT of the abdomen and pelvic ultrasonography did not show alterations at a 3 years follow-up.

Topics: Androgens; Biomarkers, Tumor; Diabetes Mellitus, Type 2; Estradiol; Female; Follicle Stimulating Hormone; Hirsutism; Humans; Hypertension; Inhibins; Keratins; Luteinizing Hormone; Middle Aged; Neoplasms, Gonadal Tissue; Obesity; Ovarian Neoplasms; Ovariectomy; Virilism