Lower Intrinsic ADP-Stimulated Mitochondrial Respiration Underlies In Vivo Mitochondrial Dysfunction in Muscle of Male Type 2 Diabetic Patients

OBJECTIVE—A lower in vivo mitochondrial function has been reported in both type 2 diabetic patients and first-degree relatives of type 2 diabetic patients. The nature of this reduction is unknown. Here, we tested the hypothesis that a lower intrinsic mitochondrial respiratory capacity may underlie lower in vivo mitochondrial function observed in diabetic patients

Role of Receptor-Interacting Protein 140 in human fat cells

<p>Abstract</p> <p>Background</p> <p>Mice lacking <it>Receptor-interacting protein 140 (RIP140) </it>have reduced body fat which at least partly is mediated through increased lipid and glucose metabolism in adipose tissue. In humans, <it>RIP140 </it>is lower expressed in visceral white adipose tissue (WAT) of obese versus lean subjects. We investigated the role of <it>RIP140 </it>in human subcutaneous WAT, which is the major fat depot of the body.</p> <p>Methods</p> <p>Messenger RNA levels of <it>RIP140 </it>were measured in samples of subcutaneous WAT from women with a wide variation in BMI and in different human WAT preparations. <it>RIP140 </it>mRNA was knocked down with siRNA in <it>in vitro </it>differentiated adipocytes and the impact on glucose transport and mRNA levels of target genes determined.</p> <p>Results</p> <p><it>RIP140 </it>mRNA levels in subcutaneous WAT were decreased among obese compared to lean women and increased by weight-loss, but did not associate with mitochondrial DNA copy number. <it>RIP140 </it>expression increased during adipocyte differentiation <it>in vitro </it>and was higher in isolated adipocytes compared to corresponding pieces of WAT. Knock down of <it>RIP140 </it>increased basal glucose transport and mRNA levels of <it>glucose transporter 4 </it>and <it>uncoupling protein-1</it>.</p> <p>Conclusions</p> <p>Human <it>RIP140 </it>inhibits glucose uptake and the expression of genes promoting energy expenditure in the same fashion as the murine orthologue. Increased levels of human <it>RIP140 </it>in subcutaneous WAT of lean subjects may contribute to economize on energy stores. By contrast, the function and expression pattern does not support that <it>RIP140 </it>regulate human obesity.</p

Inventory of the chemicals and the exposure of the workers’ skin to these at two leather factories in Indonesia

PURPOSE: Tannery workers are exposed to hazardous chemicals. Tannery work is outsourced to newly industrialized countries (NICs) where attention into occupational health hazards is limited. In this study, we investigated the skin exposure to hazardous chemicals in tannery workers and determined the prevalence of occupational skin diseases (OSDs) at tanneries in a NIC. METHODS: A cross-sectional study on the observation of the working process and an inventory and risk assessment of the chemicals used. Classification of chemicals as potential sensitizers/irritants and a qualitative assessment of exposure to these chemicals. Workers were examined and interviewed using Nordic Occupational Skin Questionnaire-2002/LONG. RESULTS: The risk of OSDs at the investigated tanneries was mainly related to the exposure of the workers' skin to chemicals in hot and humid environmental conditions. In 472 workers, 12% reported a current OSD and 9% reported a history of OSD. In 10% of all cases, an OSD was confirmed by a dermatologist and 7.4% had an occupational contact dermatitis (OCD). We observed that personal protective equipment (PPE) used was mainly because of skin problems in the past and not as a primary protection against OSD. CONCLUSION: We observed a high frequency and prolonged exposure to many skin hazardous factors in tannery work although PPE was relatively easily available and which was generally used as a secondary preventative measure. The observed point-prevalence in this study was at the same level as that reported for other high-risk OSDs in Western countries and other tanneries in NICs. However, the observed point-prevalence in this study was lower than that reported in India and Korea. The results of our study and those of other studies at tanneries from other NICs were probably influenced by Healthy Worker Survivor Effect (HWSE)

Monomeric Tartrate Resistant Acid Phosphatase Induces Insulin Sensitive Obesity

Obesity is associated with macrophage infiltration of adipose tissue, which may link adipose inflammation to insulin resistance. However, the impact of inflammatory cells in the pathophysiology of obesity remains unclear

Pregnancy in Obese Mice Protects Selectively against Visceral Adiposity and Is Associated with Increased Adipocyte Estrogen Signalling

Maternal obesity is linked with increased adverse pregnancy outcomes for both mother and child. The metabolic impact of excessive fat within the context of pregnancy is not fully understood. We used a mouse model of high fat (HF) feeding to induce maternal obesity to identify adipose tissue-mediated mechanisms driving metabolic dysfunction in pregnant and non-pregnant obese mice. As expected, chronic HF-feeding for 12 weeks preceding pregnancy increased peripheral (subcutaneous) and visceral (mesenteric) fat mass. However, unexpectedly at late gestation (E18.5) HF-fed mice exhibited a remarkable normalization of visceral but not peripheral adiposity, with a 53% reduction in non-pregnant visceral fat mass expressed as a proportion of body weight (P<0.001). In contrast, in control animals, pregnancy had no effect on visceral fat mass proportion. Obesity exaggerated glucose intolerance at mid-pregnancy (E14.5). However by E18.5, there were no differences, in glucose tolerance between obese and control mice. Transcriptomic analysis of visceral fat from HF-fed dams at E18.5 revealed reduced expression of genes involved in de novo lipogenesis (diacylglycerol O-acyltransferase 2--Dgat2) and inflammation (chemokine C-C motif ligand 20--Ccl2) and upregulation of estrogen receptor α (ERα) compared to HF non pregnant. Attenuation of adipose inflammation was functionally confirmed by a 45% reduction of CD11b+CD11c+ adipose tissue macrophages (expressed as a proportion of all stromal vascular fraction cells) in HF pregnant compared to HF non pregnant animals (P<0.001). An ERα selective agonist suppressed both de novo lipogenesis and expression of lipogenic genes in adipocytes in vitro. These data show that, in a HF model of maternal obesity, late gestation is associated with amelioration of visceral fat hypertrophy, inflammation and glucose intolerance, and suggest that these effects are mediated in part by elevated visceral adipocyte ERα signaling