The gut microbiota is interlinked with obesity, but direct evidence of effects of its modulation on body fat mass is still scarce. We investigated the possible effects of Bifidobacterium animalisssp. lactis 420 (B420) and the dietary fiber Litesse® Ultra polydextrose (LU) on body fat mass and other obesity-related parameters. 225 healthy volunteers (healthy, BMI 28-34.9) were randomized into four groups (1:1:1:1), using a computer-generated sequence, for 6months of double-blind, parallel treatment: 1) Placebo, microcrystalline cellulose, 12g/d; 2) LU, 12g/d; 3) B420, 1010CFU/d in microcrystalline cellulose, 12g/d; 4) LU+B420, 12g+1010CFU/d. Body composition was monitored with dual-energy X-ray absorptiometry, and the primary outcome was relative change in body fat mass, comparing treatment groups to Placebo. Other outcomes included anthropometric measurements, food intake and blood and fecal biomarkers. The study was registered in Clinicaltrials.gov (NCT01978691). There were marked differences in the results of the Intention-To-Treat (ITT; n=209) and Per Protocol (PP; n=134) study populations. The PP analysis included only those participants who completed the intervention with >80% product compliance and no antibiotic use. In addition, three participants were excluded from DXA analyses for PP due to a long delay between the end of intervention and the last DXA measurement. There were no significant differences between groups in body fat mass in the ITT population. However, LU+B420 and B420 seemed to improve weight management in the PP population. For relative change in body fat mass, LU+B420 showed a-4.5% (-1.4kg, P=0.02, N=37) difference to the Placebo group, whereas LU (+0.3%, P=1.00, N=35) and B420 (-3.0%, P=0.28, N=24) alone had no effect (overall ANOVA P=0.095, Placebo N=35). A post-hoc factorial analysis was significant for B420 (-4.0%, P=0.002 vs. Placebo). Changes in fat mass were most pronounced in the abdominal region, and were reflected by similar changes in waist circumference. B420 and LU+B420 also significantly reduced energy intake compared to Placebo. Changes in blood zonulin levels and hsCRP were associated with corresponding changes in trunk fat mass in the LU+B420 group and in the overall population. There were no differences between groups in the incidence of adverse events. This clinical trial demonstrates that a probiotic product with or without dietary fiber controls body fat mass. B420 and LU+B420 also reduced waist circumference and food intake, whereas LU alone had no effect on the measured outcomes.

The α₂‐adrenoceptors are G‐protein‐coupled receptors that mediate many of the physiological effects of norepinephrine and epinephrine. Mammals have three subtypes of α₂‐adrenoceptors, α_2A, α_2B and α_2C. Zebrafish, a teleost fish used widely as a model organism, has five distinct α₂‐adrenoceptor genes. The zebrafish has emerged as a powerful tool to study development and genetics, with many mutations causing diseases reminiscent of human diseases. Three of the zebrafish adra2 genes code for orthologues of the mammalian α₂‐adrenoceptors, while two genes code for α_2Da‐ and α_2Db‐ adrenoceptors, representing a duplicated, fourth α₂‐adrenoceptor subtype. The three different mammalian α₂‐adrenoceptor subtypes have distinct expression patterns in different organs and tissues, and mediate different physiological functions. The zebrafish α₂‐adrenergic system, with five different α₂‐adrenoceptors, appears more complicated. In order to deduce the physiological functions of the zebrafish α₂‐adrenoceptors, we localized the expression of the five different α₂‐adrenoceptor subtypes using RT–PCR, mRNA in situ hybridization, and receptor autoradiography using the radiolabelled α₂‐adrenoceptor antagonist [ethyl‐³H]RS‐79948–197. Localization of the α_2A‐, α_2B‐ and α_2C‐adrenoceptors in zebrafish shows marked conservation when compared with mammals. The zebrafish α_2A, α_2Da, and α_2Db each partially follow the distribution pattern of the mammalian α_2A: a possible indication of subfunction partitioning between these subtypes. The α₂‐adrenergic system is functional in zebrafish also in vivo, as demonstrated by marked locomotor inhibition, similarly to mammals, and lightening of skin colour induced by the specific α₂‐adrenoceptor agonist, dexmedetomidine. Both effects were antagonized by the specific α₂‐adrenoceptor antagonist atipamezole.

Follow-up of β-amyloid (Aβ) deposition in transgenic mouse models of Alzheimer disease (AD) would be a valuable translational tool in the preclinical evaluation of potential antiamyloid therapies. This study aimed to evaluate the ability of the clinically used PET tracer ¹¹C-Pittsburgh compound B (¹¹C-PIB) to detect changes over time in Aβ deposition in the brains of living mice representing the APP23, Tg2576, and APP_swe-PS1_dE9 transgenic mouse models of AD. Methods: Mice from each transgenic strain were imaged with 60-min dynamic PET scans at 7−9, 12, 15, and 18−22 mo of age. Regional ¹¹C-PIB retention was quantitated as distribution volume ratios using Logan graphical analysis with cerebellar reference input, as radioactivity uptake ratios between the frontal cortex (FC) and the cerebellum (CB) during the 60-min scan, and as bound-to-free ratios in the late washout phase (40−60 min). Ex vivo autoradiography experiments were performed after the final imaging session to validate ¹¹C-PIB binding to Aβ deposits. Additionally, the presence of Aβ deposits was evaluated in vitro using staining with thioflavin-S and Aβ_1–40, Aβ_1–16, and Aβ_N3(pE) immunohistochemistry. Results: Neocortical ¹¹C-PIB retention was markedly increased in old APP23 mice with large thioflavin-S–positive Aβ deposits. At 12 mo, the Logan distribution volume ratio for the FC was 1.03 and 0.93 (n = 2), increasing to 1.38 ± 0.03 (n = 3) and 1.34 (n = 1) at 18 and 21 mo of age, respectively. An increase was also observed in bound-to-free ratios for the FC between young (7- to 12-mo-old) and old (15- to 22-mo-old) APP23 mice. Binding of ¹¹C-PIB to Aβ-rich cortical regions was also evident in ex vivo autoradiograms of APP23 brain sections. In contrast, no increases in ¹¹C-PIB retention were observed in aging Tg2576 or APP_swe-PS1_dE9 mice in vivo, although in the latter, extensive Aβ deposition was already observed at 9 mo of age with immunohistochemistry. Conclusion: The results suggest that ¹¹C-PIB binding to Aβ deposits in transgenic mouse brain is highly dependent on the AD model and the structure of its Aβ plaques. Longitudinal in vivo ¹¹C-PIB uptake studies are possible in APP23 mice.