Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism

Objectives Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome\u27s functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation. Design We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice. Results Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration. Conclusion Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity

Nouvelles adipokines

International audienceAdipose tissue is now widely recognized as “an organ” able to synthesize and secrete hundred factors collectively called adipokines. These secreted molecules exert pleiotropic actions, notably on the regulation of glucose and lipid metabolism, inflammation, reproduction, or angiogenesis. Over the past two decades, a considerable amount of work was performed on the two “star” adipokines, leptin and adiponectin, particularly because of their involvement in energy metabolism. The present review is focused on the three most recently discovered adipokines that are clearly emerging as important actors in metabolism: apelin, fibroblast growth factor-21, and neuroregulin-4. Moreover, given a number of clinical and experimental data, these three adipokines represent promising targets in the context of metabolic disorders associated with obesity.Le tissu adipeux est désormais largement reconnu en tant qu’« organe » capable de synthétiser et de sécréter de nombreux facteurs rassemblés sous le terme d’adipokines. Ce tissu sécrète vraisemblablement plusieurs centaines de molécules, qui exercent des actions pléiotropes, notamment sur la régulation du métabolisme glucido-lipidique, l’inflammation, la reproduction, ou l’angiogenèse. Au cours des deux dernières décennies, une somme considérable de travaux a été réalisée sur les adipokines « vedettes », la leptine et l’adiponectine, notamment en raison de leur implication dans le métabolisme énergétique. De parti pris, cette revue est focalisée sur trois adipokines de découverte plus récente, mais dont l’intérêt émerge clairement : l’apéline, le FGF21, et la neuroréguline-4. Au vu de plusieurs données cliniques et expérimentales, ces trois adipokines représentent des cibles prometteuses dans le contexte des désordres métaboliques associés à l’obésité

Adipokines in Semen: Physiopathology and Effects on Spermatozoas

Adipokines are secreted by adipose tissue and could be the link between obesity and infertility. Different studies investigated the involvement of adipokines in reproductive functions but only a few have looked into the male part. This review assesses adipokine functions on male reproductive parameters. Adiponectin seems to have a positive effect on sperm parameters, whereas other adipokines such as resistin or chemerin would have a rather deleterious effect on spermatogenesis. Semen parameters seem to be impacted when resistin and chemerin are increased: indeed, there is a decrease of sperm motility. Sperm morphology is improved when adiponectin is increased. The most studied adipokine, leptin, has a dual effect with a positive effect on sperm at physiological levels and a negative one for high seminal concentrations. Many semen parameters and fertility itself are disturbed according to semen adipokine levels, even if it is not the only interfering element. Taken together, adipokines are found in human and animal semen and most of them or their receptors are expressed in male genital tract. Although the pathophysiological role of adipokines in semen is not clearly elucidated, the adipokines could influence sperm functionality and could be potential biomarkers of male fertility

Response to 'Serum level of adiponectin is a surrogate independent biomarker of radiographic disease progression in early rheumatoid arthritis: results from the ESPOIR cohort' - authors' reply

International audienc

Aside from acute renal failure cases, are urinary markers of glomerular and tubular function useful in clinical practice?

International audienc

Seminal plasma adipokines: involvement in human reproductive functions

International audienceInfertility, which increased worldwide over the past few decades, has recently been linked to obesity prevalence. Adipokines, produced by adipose tissue, could be the link between obesity and infertility. The association between circulating adipokines and female infertility has been extensively studied in the last ten years. However, the male aspect has been less investigated, although some adipokines are present in seminal plasma. We have attempted to analyze published studies that measured seminal plasma adipokines and their relationships with semen parameters. Apart from leptin, other seminal adipokines have rarely been studied. Indeed, leptin seems to have a differential role depending on its concentration in the seminal plasma. Thus, it could have a beneficial effect at lower concentrations but a deleterious effect at higher seminal levels. Although some studies are currently available, the roles of leptin and other adipokines in seminal plasma on sperm parameters and their consequences on male fertility remain to be clarified

Metabolic complications affecting adipose tissue, lipid and glucose metabolism associated with HIV antiretroviral treatment

International audienceIntroduction: Efficient antiretroviral-treatment (ART) generally allows control of HIV infection. However, persons-living-with-HIV (PLWH), when aging, present a high prevalence of metabolic diseases.Area covered: Altered adiposity, dyslipidemias, insulin resistance, diabetes, and their consequences are prevalent in PLWH and could be partly related to ART.Expert opinion: At first, personal and lifestyle factors are involved in the onset of these complications. The persistence of HIV in tissue reservoirs could synergize with some ART and enhance metabolic disorders. Altered fat repartition, diagnosed as lipodystrophy, has been related to first-generation nucleoside-reverse-transcriptase-inhibitors (NRTIs) (stavudine zidovudine) and some protease inhibitors (PIs). Recently, use of some integrase-inhibitors (INSTI) resulted in weight/fat gain, which represents a worrisome unresolved situation. Lipid parameters were affected by some first-generation NRTIs, non-NRTIs (efavirenz) but also PIs boosted by ritonavir, with increased total and LDL-cholesterol and triglycerides. Insulin resistance is common associated with abdominal obesity. Diabetes incidence, high with first-generation-ART (zidovudine, stavudine, didanosine, indinavir) has declined with contemporary ART close to that of the general population. Metabolic syndrome, a dysmetabolic situation with central obesity and insulin resistance, and liver steatosis are common in PLWH and could indirectly result from ART-associated fat gain and insulin resistance. All these dysmetabolic situations increase the atherogenic cardiovascular risk

Optimization of pre-analytical conditions for measurement of biomarkers in seminal plasma: application to adipokines

International audienceA link between obesity and male infertility, concerning particularly semen quality, has been reported. Indeed, circulating levels of adipokines, bioactive peptides secreted by adipose tissue, are correlated with sperm quality in both animals and humans. In this context, levels of adipokines in seminal plasma could influence sperm function and represent useful biomarkers to evaluate fertility-related physiological and pathophysiological conditions

Expériences d’accréditation des électrophorèses sériques et urinaires

International audienc