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

ObjectivesGut 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’s 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.DesignWe 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.ResultsSevere 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.ConclusionStrategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity.Trial registration numberNCT02059538.

Muscle adaptation to sleeve gastrectomy: Potential role of nutritional supplementation and physical exercise

Skeletal muscle is metabolically and functionally flexible and contractile under normal conditions. Obesity is a risk factor that causes metabolic disorders and reduces muscle contractility. Sleeve gastrectomy (SG) has been used for surgical correction of obesity. This work aimed to investigate how obesity and its surgical correction affects skeletal muscle and the possible role of nutritional supplementation and physical exercise. Adult male albino rats were randomly divided into five groups, 8 rats per group: group Ia (control non-obese), group Ib (control obese), group II (post-operative, SG), group III (post SG + nutritional supplementation) and group IV (post SG + nutritional supplementation + physical exercise). SG resulted in cellular and metabolic degenerative disorders in the muscle including wasting, weakness and fibrosis with elevated inflammatory, oxidative and injury markers. Nutritional supplementation induced the post SG muscle regeneration indicated by high expression of insulin growth factor-1 (IGF-1) and myogenin and low expression of transforming growth factor beta 1 (TGF-β1). Interestingly, it improved the metabolic state of the muscle by reducing the oxidative stress, inflammatory and muscle injury markers and delaying the onset of fatigue. What is more, physical exercise along with nutritional supplementation resulted in further improvement of the muscle metabolic state and function. In conclusion, nutritional supplementations together with physical exercise after SG are essential for preserving muscle mass and contractility and improving its metabolic and functional status.

Mitochondria in Early Forebrain Development: From Neurulation to Mid-Corticogenesis

Function of the mature central nervous system (CNS) requires a substantial proportion of the body’s energy consumption. During development, the CNS anlage must maintain its structure and perform stage-specific functions as it proceeds through discrete developmental stages. While key extrinsic signals and internal transcriptional controls over these processes are well appreciated, metabolic and mitochondrial states are also critical to appropriate forebrain development. Specifically, metabolic state, mitochondrial function, and mitochondrial dynamics/localization play critical roles in neurulation and CNS progenitor specification, progenitor proliferation and survival, neurogenesis, neural migration, and neurite outgrowth and synaptogenesis. With the goal of integrating neurodevelopmental biologists and mitochondrial specialists, this review synthesizes data from disparate models and processes to compile and highlight key roles of mitochondria in the early development of the CNS with specific focus on forebrain development and corticogenesis.

Impact of Pre-Mortem Factors on Meat Quality: An Update

Meat quality is closely associated with the chemical composition of skeletal muscle and is therefore influenced by the pre-mortem metabolic state of skeletal muscle tissue [...]

PGC-1α in the myofibers regulates the balance between myogenic and adipogenic progenitors affecting muscle regeneration

Skeletal muscle repair is accomplished by satellite cells (MuSC) in cooperation with interstitial stromal cells (ISCs). So far, the relationship between the function of these cells and the metabolic state of myofibers remains unclear. The present study reports alterations in the proportion of both MuSCs and adipogenesis regulators (Aregs) induced by overexpression of peroxisome proliferator-activated receptor gamma coactivator 1–alpha (PGC–1α) in the myofibers (MCK–PGC–1α mice). Although PGC-1α–driven increase of MuSCs does not accelerate muscle regeneration, myogenic progenitors isolated from MCK–PGC–1α mice and transplanted into intact and regenerating muscles are more prone to fuse with recipient myofibers than those derived from WT donors. Moreover, both young and aged MCK-PGC-1α animals show reduced perilipin-positive areas when challenged with an adipogenic stimulus, demonstrating low propensity to accumulate adipocytes within the muscle. These results provide new insights on the role played by PGC–1α in promoting myogenesis and hindering adipogenesis in the skeletal muscle.

Hyperkinetic Movement Disorders: Tremor and Myoclonus

Hyperkinetic movement disorders are characterized by excess movement. Tremor and myoclonus are the most common hyperkinetic movement disorders and signify various possible underlying causes or diagnoses. Tremor is an involuntary, rhythmic, oscillatory movement of a body part. It can be distinguished from myoclonus by its regular frequency and from chorea by its stereotyped nature. The subtypes of tremor vary in frequency, conditions of activation and relief, and associated signs and symptoms. Tremor can be primary, being the only manifestation of a condition, or secondary, being symptomatic of a metabolic state or other underlying disease.