Effects of Bifidobacterium animalis Subsp. lactis (BPL1) Supplementation in Children and Adolescents with Prader-Willi Syndrome : A Randomized Crossover Trial

Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by a wide range of clinical manifestations, including obesity, hyperphagia, and behavioral problems. Bifidobacterium animalis subsp. lactis strain BPL1 has been shown to improve central adiposity in adults with simple obesity. To evaluate BPL1's effects in children with PWS, we performed a randomized crossover trial among 39 patients (mean age 10.4 years). Participants were randomized to placebo-BPL1 (n = 19) or BPL1-placebo (n = 20) sequences and underwent a 12-week period with placebo/BPL1 treatments, a 12-week washout period, and a 12-week period with the crossover treatment. Thirty-five subjects completed the study. The main outcome was changes in adiposity, measured by dual-energy X-ray absorptiometry. Secondary outcomes included lipid and glucose metabolism, hyperphagia, and mental health symptoms. Generalized linear modeling was applied to assess differences between treatments. While BPL1 did not modify total fat mass compared to placebo, BPL1 decreased abdominal adiposity in a subgroup of patients older than 4.5 years (n = 28). BPL1 improved fasting insulin concentration and insulin sensitivity. Furthermore, we observed modest improvements in some mental health symptoms. A follow-up trial with a longer treatment period is warranted to determine whether BPL1 supplementation can provide a long-term therapeutic approach for children with PWS (ClinicalTrials.gov NCT03548480)

Effects of Bifidobacterium animalis Subsp. lactis (BPL1) Supplementation in Children and Adolescents with Prader-Willi Syndrome: A Randomized Crossover Trial

Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by a wide range of clinical manifestations, including obesity, hyperphagia, and behavioral problems. Bifidobacterium animalis subsp. lactis strain BPL1 has been shown to improve central adiposity in adults with simple obesity. To evaluate BPL1's effects in children with PWS, we performed a randomized crossover trial among 39 patients (mean age 10.4 years). Participants were randomized to placebo-BPL1 (n = 19) or BPL1-placebo (n = 20) sequences and underwent a 12-week period with placebo/BPL1 treatments, a 12-week washout period, and a 12-week period with the crossover treatment. Thirty-five subjects completed the study. The main outcome was changes in adiposity, measured by dual-energy X-ray absorptiometry. Secondary outcomes included lipid and glucose metabolism, hyperphagia, and mental health symptoms. Generalized linear modeling was applied to assess differences between treatments. While BPL1 did not modify total fat mass compared to placebo, BPL1 decreased abdominal adiposity in a subgroup of patients older than 4.5 years (n = 28). BPL1 improved fasting insulin concentration and insulin sensitivity. Furthermore, we observed modest improvements in some mental health symptoms. A follow-up trial with a longer treatment period is warranted to determine whether BPL1 supplementation can provide a long-term therapeutic approach for children with PWS (ClinicalTrials.gov NCT03548480)

Increasing breast milk betaine modulates Akkermansia abundance in mammalian neonates and improves long-term metabolic health

Accelerated postnatal growth is a potentially modifiable risk factor for future obesity. To study how specific breast milk components contribute to early growth and obesity risk, we quantified one-carbon metabolism-related metabolites in human breast milk and found an inverse association between milk betaine content and infant growth. This association was replicated in an independent and geographically distinct cohort. To determine the potential role of milk betaine in modulating offspring obesity risk, we performed maternal betaine supplementation experiments in mice. Higher betaine intake during lactation increased milk betaine content in dams and led to lower adiposity and improved glucose homeostasis throughout adulthood in mouse offspring. These effects were accompanied by a transient increase in Akkermansia spp. abundance in the gut during early life and a long-lasting increase in intestinal goblet cell number. The link between breast milk betaine and Akkermansia abundance in the gut was also observed in humans, as infants exposed to higher milk betaine content during breastfeeding showed higher fecal Akkermansia muciniphila abundance. Furthermore, administration of A. muciniphila to mouse pups during the lactation period partially replicated the effects of maternal breast milk betaine, including increased intestinal goblet cell number, lower adiposity, and improved glucose homeostasis during adulthood. These data demonstrate a link between breast milk betaine content and long-term metabolic health of offspring.info:eu-repo/semantics/acceptedVersio

Early nutrition reprograms the hepatic circadian clock: Permanent deregulation of metabolism

Póster presentado al XXXVII Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Granada del 9 al 12 de septiembre de 2014.-- et al.Excessive caloric intake during early stages of development increases the risk of childhood obesity and predisposes individuals to develop late onset of obesity, insulin resistance and type 2 diabetes. We have developed a mouse model of neonatal overfeeding (ON) by culling the offspring to 4 pups per dam during lactation. Control females nursed 8 pups during lactation (C). ON mice developed obesity, hyperglycaemia, insulin resistance and glucose intolerance with ageing. The liver was the tissue that contributed most prominently to the development of insulin resistance. In order to underpin molecular mechanisms of insulin resistance we analysed global gene expression profiling (Affymetrix) in livers from ON and C male mice. The Ontology with highest signifi cance was the Circadian Rhythm. We next validated (qPCR) the candidate genes (Npas2, Per1, Per3, Cry1) in adult mice. Strikingly, changes in expression (Per1, Cry2) were already present in livers from 15-day-old ON mice. This data suggests that altered expression of hepatic clock genes is established early in life and do not occur as a secondary event associated to the progressive development of obesity and/or insulin resistance. Circadian rhythms play a major role in orchestrating daily physiological functions, and disrupting the expression of clock genes evokes metabolic diseases. Thus, we tested whole-body metabolism by indirect calorimetry. We found that VO2, VCO2, energy expenditure or activity absolute values were similar between groups during both the light and dark cycles. In contrast, in agreement with alterations in the circadian rhythmicity, the diurnal decrease in respiratory exchange ratio (RER) cycling started signifi cantly earlier in ON mice. Likewise, upon fasting, V02, VCO2, and energy expenditure remained higher in ON mice during the night cycle. Overall, we show that early malnutrition permanently reprograms the hepatic circadian clock. Such reprogramming induces a sustained feedback loop that may in turn infl uence the physiologic behaviour of mice leading, secondarily, to overall metabolic deregulation.Peer reviewe

The long-lasting shadow of litter size in rodents: litter size is an underreported variable that strongly determines adult physiology.

BACKGROUND/PURPOSE: Litter size is a biological variable that strongly influences adult physiology in rodents. Despite evidence from previous decades and recent studies highlighting its major impact on metabolism, information about litter size is currently underreported in the scientific literature. Here, we urge that this important biological variable should be explicitly stated in research articles. RESULTS/CONCLUSION: Below, we briefly describe the scientific evidence supporting the impact of litter size on adult physiology and outline a series of recommendations and guidelines to be implemented by investigators, funding agencies, editors in scientific journals, and animal suppliers to fill this important gap

Effects of Bifidobacterium animalis Subsp. lactis (BPL1) Supplementation in Children and Adolescents with Prader–Willi Syndrome: A Randomized Crossover Trial

Prader–Willi syndrome (PWS) is a rare genetic disorder characterized by a wide range of clinical manifestations, including obesity, hyperphagia, and behavioral problems. Bifidobacterium animalis subsp. lactis strain BPL1 has been shown to improve central adiposity in adults with simple obesity. To evaluate BPL1′s effects in children with PWS, we performed a randomized crossover trial among 39 patients (mean age 10.4 years). Participants were randomized to placebo–BPL1 (n = 19) or BPL1–placebo (n = 20) sequences and underwent a 12-week period with placebo/BPL1 treatments, a 12-week washout period, and a 12-week period with the crossover treatment. Thirty-five subjects completed the study. The main outcome was changes in adiposity, measured by dual-energy X-ray absorptiometry. Secondary outcomes included lipid and glucose metabolism, hyperphagia, and mental health symptoms. Generalized linear modeling was applied to assess differences between treatments. While BPL1 did not modify total fat mass compared to placebo, BPL1 decreased abdominal adiposity in a subgroup of patients older than 4.5 years (n = 28). BPL1 improved fasting insulin concentration and insulin sensitivity. Furthermore, we observed modest improvements in some mental health symptoms. A follow-up trial with a longer treatment period is warranted to determine whether BPL1 supplementation can provide a long-term therapeutic approach for children with PWS (ClinicalTrials.gov NCT03548480)

Triglyceride levels in skm, liver and adipose tissue of GFP- and FATP1-mice.

<p>Triglyceride levels were measured in extracts from the gastrocnemius muscle, liver and white adipose tissue of <i>ad libitum</i> fed GFP- or FATP1-mice. Data are means ± SEM of at least four samples. The significance of the Student's t test is: ^*p<0.05 and ^**p<0.001 female versus male GFP-mice fed chow; ^#p<0.01 female versus male FATP1-mice fed chow; ^†p<0.05 and ^††p<0.001 female GFP-mice fed high-fat versus chow; ^‡p<0.05 and ^‡‡p<0.001 female FATP1-mice fed high-fat versus chow; and ^¥p<0.05 FATP1- versus GFP-mice irrespective of diet and gender.</p

β-hydroxybutyrate levels in skm and liver of high-fat diet fed GFP- and FATP1-mice.

<p>β-hydroxybutyrate levels were measured in extracts from the gastrocnemius and tibialis anterior muscle and the liver of GFP- and FATP1-female mice fed high-fat. Data are mean values ± SEM from four to five samples.</p

Effects of FATP1 overexpression on gastrocnemius muscle palmitate, β-hydroxybutyrate and glucose oxidation.

<p>Gastrocnemius muscle strips were prepared from pGFP- or pFATP1-electropored mice. (A) The FATP1 protein levels relative to α-tubulin levels were determined in total extracts and the 1500 <i>g</i> pellet fraction (20 µg of protein) by immunoblotting. Bands were quantified with a LAS-3000 (FujiFilm). Data is the ratio of intensities of bands in arbitrary units and is the mean ± SEM of at least five samples. (B) Muscle strips were incubated for 4 h with radioactively labelled palmitate (PA), β-hydroxybutyrate (BHB) or glucose (GLU). At the end of this period, substrate utilization rate, ¹⁴CO₂ production rate (and [¹⁴C]acid-soluble intermediate metabolites (ASI) production rate in palmitate-incubated strips) were determined. Data are expressed as a percentage of control and are the means ± SEM of seven muscle samples. (A,B) The significance of the Student's t test versus controls is *p<0.05.</p

Electron microscopic localization of FATP1-GFP in C2C12 myotubes.

<p>C2C12 myoblasts were transfected with (a,b) pFATP1-GFP or (c) pGFP (control), and induced to differentiate into myotubes. Four days post-transfection, myotubes were fixed, gelatin blocks mounted and sections were prepared in an ultracryomicrotome, incubated with anti-GFP antibody and analyzed by electronic microscopy. (a,b) Image of FATP1-GFP localized inside the mitochondria (see arrows); (c) image of GFP localized in the Golgi complex (see continuous arrows) and nuclei (dotted arrow). The observations were made in an electron microscope with a CCD camera and an electron accelerating voltage of 80 Kv was employed for the measurements. Bar represents 200 nm.</p