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Interspecies hydrogen transfer in anoxic ecosystems is essential for the complete microbial breakdown of organic matter to methane. Acetogenic bacteria are key players in anaerobic food webs and have been considered as prime candidates for hydrogen cycling. We have tested this hypothesis by mutational analysis of the hydrogenase in the model acetogen Acetobacterium woodii. Hydrogenase-deletion mutants no longer grew on H2 + CO2 or organic substrates such as fructose, lactate, or ethanol. Heterotrophic growth could be restored by addition of molecular hydrogen to the culture, indicating that hydrogen is an intermediate in heterotrophic growth. Indeed, hydrogen production from fructose was detected in a stirred-tank reactor. The mutant grew well on organic substrates plus caffeate, an alternative electron acceptor that does not require molecular hydrogen but NADH as reductant. These data are consistent with the notion that molecular hydrogen is produced from organic substrates and then used as reductant for CO2 reduction. Surprisingly, hydrogen cycling in A. woodii is different from the known modes of interspecies or intraspecies hydrogen cycling. Our data are consistent with a novel type of hydrogen cycling that connects an oxidative and reductive metabolic module in one bacterial cell, "intracellular syntrophy."BACKGROUND G protein-coupled receptors (GPCR) are well-characterized regulators of a plethora of physiological functions among them the modulation of adipogenesis and adipocyte function. The class of Adhesion GPCR (aGPCR) and their role in adipose tissue, however, is poorly studied. With respect to the demand for novel targets in obesity treatment, we present a comprehensive study on the expression and function of this enigmatic GPCR class during adipogenesis and in mature adipocytes. METHODS The expression of all aGPCR representatives was determined by reanalyzing RNA-Seq data and by performing qPCR in different mouse and human adipose tissues under low- and high-fat conditions. The impact of aGPCR expression on adipocyte differentiation and lipid accumulation was studied by siRNA-mediated knockdown of all expressed members of this receptor class. The biological characteristics and function of mature adipocytes lacking selected aGPCR were analyzed by mass spectrometry and biochemical methods (lipolysis, glucose uptake, adiponectin secretion). RESULTS More than ten aGPCR are significantly expressed in visceral and subcutaneous adipose tissues and several aGPCR are differentially regulated under high-caloric conditions in human and mouse. Receptor knockdown of six receptors resulted in an impaired adipogenesis indicating their expression is essential for proper adipogenesis. The altered lipid composition was studied in more detail for two representatives, ADGRG2/GPR64 and ADGRG6/GPR126. While GPR126 is mainly involved in adipocyte differentiation, GPR64 has an additional role in mature adipocytes by regulating metabolic processes. CONCLUSIONS Adhesion GPCR are significantly involved in qualitative and quantitative adipocyte lipid accumulation and can control lipolysis. Factors driving adipocyte formation and function are governed by signaling pathways induced by aGPCR yielding these receptors potential targets for treating obesity.BACKGROUND Recent evidence indicates that insulin resistance (IR) in obesity may develop independently in different organs, representing different etiologies toward type 2 diabetes and other cardiometabolic diseases. The aim of this study was to investigate whether IR in the liver and IR in skeletal muscle are associated with distinct metabolic profiles. METHODS This study includes baseline data from 634 adults with overweight or obesity (BMI ≥ 27 kg/m2) (≤65 years; 63% women) without diabetes of the European Diogenes Study. selleck chemicals Hepatic insulin resistance index (HIRI) and muscle insulin sensitivity index (MISI), were derived from a five-point OGTT. At baseline 17 serum metabolites were identified and quantified by nuclear-magnetic-resonance spectroscopy. Linear mixed model analyses (adjusting for center, sex, body mass index (BMI), waist-to-hip ratio) were used to associate HIRI and MISI with these metabolites. In an independent sample of 540 participants without diabetes (BMI ≥ 27 kg/m2; 40-65 years; 46% women) wledge might enhance developments of more targeted tissue-specific interventions to prevent progression to more severe disease stages.BACKGROUND Previous studies have reported that high-dose supplementation of n-3 polyunsaturated fatty acids (PUFAs) may reduce the risk of metabolic diseases, but there is limited evidence of an effect on body fat. We examined the associations of erythrocyte n-3 PUFAs with body fat and fat distribution in a general population consuming a normal diet. METHODS This community-based cross-sectional study included 3075 Chinese (68% women, 40-75 years) recruited between 2008 and 2013. We collected general information and measured anthropometric indices; erythrocyte n-3 PUFAs (including α-C183, C205, C225 and C226) by gas-chromatography, and fat mass (FM) and %FM at the total body (TB), android (A) and gynoid (G) regions by dual-energy X-ray absorptiometry (DXA). RESULTS Both minimally and maximally adjusted models showed dose-dependent inverse associations of total and individual levels of erythrocyte n-3 PUFAs (except C205 n-3[EPA]) with adiposity indices. In the full model, the mean differences between quartiles 4 and 1 of total n-3 PUFAs were -1.60% (BMI), -4.06% (TB FM), -5.38% (A FM), -2.05% (G FM), -2.05% (TB %FM), -3.39% (A %FM) and -2.50% (% A/G); the ORs (95% CI) of %FM-derived obesity (≥25% for men, ≥35% for women) for the highest (vs. lowest) quartile were 0.70 (0.57, 0.86) for total n-3 PUFAs and 0.71 (0.58, 0.87), 0.96(0.78, 1.18), 0.82(0.67, 1.00), 0.66 (0.54, 0.81) for α-C183/C205/C225/C226 n-3, respectively. The favourable associations were more pronounced for the DXA-derived FM indices, measurements at the android region and for C226 n-3. No significant associations between C205 n-3 and the adiposity indices were observed. CONCLUSIONS Higher levels of circulating n-3 PUFAs were dose-dependently associated with better profiles of body fat and fat distribution, particularly in the abdominal regions in this population.
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