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Mixed martial arts' popularity has increased in recent years, alongside descriptive research and evidence-based performance recommendations. Guidelines for (both chronic and acute) weight making exist; however, how these translate in real-life scenarios and detailed investigations on practices in larger groups deserve attention. The present study examined the body mass (BM) and composition of 33 professional mixed martial arts athletes preparing for 80 fights. Athletes were supported by on-site dietitians, who encouraged evidence-based practices. Fasted BM was measured throughout the last ∼10 days before all bouts (acute weight management phase). A subset of athletes had body composition assessed before and after the chronic weight loss phase for 40 fights. Most athletes engaged in chronic BM loss, and all engaged in acute weight loss. Many lost fat-free mass (FFM) during the chronic phase, with rates of BM loss <0.5% best preserving FFM. Regardless of losses, the present athletes possessed greater FFM than other combat sport athletes and engaged in greater acute weight loss. Dehydration in the 24–48 hr before the weigh-in was not reflective of weight regain after the weigh-in, rather BM 7–10 days before the weigh-in was most reflective. These findings suggest that many mixed martial arts athletes could increase FFM at the time of competition by maintaining leaner physiques outside of competition and/or allowing increased time to reduce BM chronically. Acutely, athletes can utilize evidence-based protocols, eliminating carbohydrates, fiber, sodium, and finally fluid in a staged approach, before the weigh-in, reducing the amount of sweating required, thus theoretically better protecting health and preserving performance. [ABSTRACT FROM AUTHOR]

A hybrid quantum mechanics/molecular mechanics setup was used to model electronically excited pentacene in the crystal phase. Particularly interesting in the context of singlet fission (SF) is the energetic location of the antiferromagnetically coupled multiexcitonic singlet state, 1(TT), and the ferromagnetically coupled analog in relation to the optically bright singlet state. To provide photophysical properties of the accessible spin manifold, combined density functional theory and multi-reference configuration interaction calculations were performed on pentacene dimers and a trimer, electrostatically embedded in the crystal. The likelihood of a quintet intermediate in the SF process was estimated by computing singlet–quintet electron spin–spin couplings employing the Breit–Pauli Hamiltonian. The performance of the applied methods was assessed on the pentacene monomer. The character of the optically bright state and the energetic location of the 1(TT) state depend strongly on the relative orientation of the pentacene units. In the V-shaped dimers and in the trimer, the optically bright state is dominated by local and charge transfer (CT) excitations, with admixtures of doubly excited configurations. The CT excitations gain weight upon geometry relaxation, thus supporting a CT-mediated SF mechanism as the primary step of the SF process. For the slip-stacked dimer, the energetic order of the bright and the 1(TT) states swaps upon geometry relaxation, indicating strong nonadiabatic coupling close to the Franck–Condon region—a prerequisite for a coherent SF process. The multiexcitonic singlet, triplet, and quintet states are energetically too far apart and their spin–spin couplings are too small to bring about a noteworthy multiplicity mixing. [ABSTRACT FROM AUTHOR]

Microbiota-directed complementary food (MDCF) formulations have been designed to repair the gut communities of malnourished children. A randomized controlled trial demonstrated that one formulation, MDCF-2, improved weight gain in malnourished Bangladeshi children compared to a more calorically dense standard nutritional intervention. Metagenome-assembled genomes from study participants revealed a correlation between ponderal growth and expression of MDCF-2 glycan utilization pathways by Prevotella copri strains. To test this correlation, here we use gnotobiotic mice colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains, with or without P. copri isolates closely matching the metagenome-assembled genomes. Combining gut metagenomics and metatranscriptomics with host single-nucleus RNA sequencing and gut metabolomic analyses, we identify a key role of P. copri in metabolizing MDCF-2 glycans and uncover its interactions with other microbes including Bifidobacterium infantis. P. copri-containing consortia mediated weight gain and modulated energy metabolism within intestinal epithelial cells. Our results reveal structure-function relationships between MDCF-2 and members of the gut microbiota of malnourished children with potential implications for future therapies.

Mitochondrial dysfunction is a characteristic trait of human and rodent obesity, insulin resistance and fatty liver disease. Here we show that high-fat diet (HFD) feeding causes mitochondrial fragmentation in inguinal white adipocytes from male mice, leading to reduced oxidative capacity by a process dependent on the small GTPase RalA. RalA expression and activity are increased in white adipocytes after HFD. Targeted deletion of RalA in white adipocytes prevents fragmentation of mitochondria and diminishes HFD-induced weight gain by increasing fatty acid oxidation. Mechanistically, RalA increases fission in adipocytes by reversing the inhibitory Ser637 phosphorylation of the fission protein Drp1, leading to more mitochondrial fragmentation. Adipose tissue expression of the human homolog of Drp1, DNM1L, is positively correlated with obesity and insulin resistance. Thus, chronic activation of RalA plays a key role in repressing energy expenditure in obese adipose tissue by shifting the balance of mitochondrial dynamics toward excessive fission, contributing to weight gain and metabolic dysfunction.

BACKGROUND: Antibiotic use during early infancy has been linked to childhood obesity in high-income countries. We evaluated whether a single oral dose of azithromycin administered during infant-well visits led to changes in infant growth outcomes at 6 months of age in a setting with a high prevalence of undernutrition in rural Burkina Faso. METHODS AND FINDINGS: Infants were enrolled from September 25, 2019, until October 22, 2022, in a randomized controlled trial designed to evaluate the efficacy of a single oral dose of azithromycin (20 mg/kg) compared to placebo when administered during well-child visits for prevention of infant mortality. The trial found no evidence of a difference in the primary endpoint. This paper presents prespecified secondary anthropometric endpoints including weight gain (g/day), height change (mm/day), weight-for-age Z-score (WAZ), weight-for-length Z-score (WLZ), length-for-age Z-score (LAZ), and mid-upper arm circumference (MUAC). Infants were eligible for the trial if they were between 5 and 12 weeks of age, able to orally feed, and their families were planning to remain in the study area for the duration of the study. Anthropometric measurements were collected at enrollment (5 to 12 weeks of age) and 6 months of age. Among 32,877 infants enrolled in the trial, 27,298 (83%) were followed and had valid anthropometric measurements at 6 months of age. We found no evidence of a difference in weight gain (mean difference 0.03 g/day, 95% confidence interval (CI) -0.12 to 0.18), height change (mean difference 0.004 mm/day, 95% CI -0.05 to 0.06), WAZ (mean difference -0.004 SD, 95% CI -0.03 to 0.02), WLZ (mean difference 0.001 SD, 95% CI -0.03 to 0.03), LAZ (mean difference -0.005 SD, 95% CI -0.03 to 0.02), or MUAC (mean difference 0.01 cm, 95% CI -0.01 to 0.04). The primary limitation of the trial was that measurements were only collected at enrollment and 6 months of age, precluding assessment of shorter-term or long-term changes in growth. CONCLUSIONS: Single-dose azithromycin does not appear to affect weight and height outcomes when administered during early infancy. TRIAL REGISTRATION: ClinicalTrials.gov NCT03676764.

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition1-4. Here we analyse biospecimens from a randomized, controlled trial of a microbiome-directed complementary food (MDCF-2) that produced superior rates of weight gain compared with a calorically more dense conventional ready-to-use supplementary food in 12-18-month-old Bangladeshi children with moderate acute malnutrition4. We reconstructed 1,000 bacterial genomes (metagenome-assembled genomes (MAGs)) from the faecal microbiomes of trial participants, identified 75 MAGs of which the abundances were positively associated with ponderal growth (change in weight-for-length Z score (WLZ)), characterized changes in MAG gene expression as a function of treatment type and WLZ response, and quantified carbohydrate structures in MDCF-2 and faeces. The results reveal that two Prevotella copri MAGs that are positively associated with WLZ are the principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilizing the component glycans of MDCF-2. The predicted specificities of carbohydrate-active enzymes expressed by their polysaccharide-utilization loci are correlated with (1) the in vitro growth of Bangladeshi P. copri strains, possessing varying degrees of polysaccharide-utilization loci and genomic conservation with these MAGs, in defined medium containing different purified glycans representative of those in MDCF-2, and (2) the levels of faecal carbohydrate structures in the trial participants. These associations suggest that identifying bioactive glycan structures in MDCFs metabolized by growth-associated bacterial taxa will help to guide recommendations about their use in children with acute malnutrition and enable the development of additional formulations.

Significant human gut microbiome changes during adolescence suggest that microbial community evolution occurs throughout important developmental periods including the transition to college, a typical life phase of weight gain. In this observational longitudinal study of 139 college freshmen living in on-campus dormitories, we tracked changes in the gut microbiome via 16S amplicon sequencing and body weight across a single academic year. Participants were grouped by weight change categories of gain (WG), loss (WL), and maintenance (WM). Upon assessment of the community structure, unweighted and weighted UniFrac metrics revealed significant shifts with substantial variation explained by individual effects within weight change categories. Genera that positively contributed to these associations with weight change included Bacteroides, Blautia, and Bifidobacterium in WG participants and Prevotella and Faecalibacterium in WL and WM participants. Moreover, the Prevotella/Bacteroides ratio was significantly different by weight change category, with WL participants displaying an increased ratio. Importantly, these genera did not display co-dominance nor ease of transition between Prevotella- and Bacteroides-dominated states. We further assessed the overall taxonomic variation, noting the increased stability of the WL compared to the WG microbiome. Finally, we found 30 latent community structures within the microbiome with significant associations with waist circumference, sleep, and dietary factors, with alcohol consumption chief among them. Our findings highlight the high level of individual variation and the importance of initial gut microbiome community structure in college students during a period of major lifestyle changes. Further work is needed to confirm these findings and explore mechanistic relationships between gut microbes and weight change in free-living individuals.