Beta-Aminoisobutyric acid (BAIBA), a thymine catabolite, increases fatty acid oxidation (FAO) in liver and reduces the gain of body fat mass in Swiss (lean) mice fed a standard chow. We determined ...whether BAIBA could prevent obesity and related metabolic disorders in different murine models. To this end, BAIBA (100 or 500 mg/kg/day) was administered for 4 months in mice totally deficient in leptin (ob/ob). BAIBA (100 mg/kg/day) was also given for 4 months in wild-type (+/+) mice and mice partially deficient in leptin (ob/+) fed a high-calorie (HC) diet. BAIBA did not limit obesity and hepatic steatosis in ob/ob mice, but reduced liver cytolysis and inflammation. In ob/+ mice fed the HC diet, BAIBA fully prevented, or limited, the gain of body fat, steatosis and necroinflammation, glucose intolerance, and hypertriglyceridemia. Plasma beta-hydroxybutyrate was increased, whereas expression of carnitine palmitoyltransferase-1 was augmented in liver and white adipose tissue. Acetyl-CoA carboxylase was more phosphorylated, and de novo lipogenesis was less induced in liver. These favorable effects of BAIBA in ob/+ mice were associated with a restoration of plasma leptin levels. The reduction of body adiposity afforded by BAIBA was less marked in +/+ mice. Finally, BAIBA significantly stimulated the secretion of leptin in isolated ob/+ adipose cells, but not in +/+ cells. Thus, BAIBA could limit triglyceride accretion in tissues through a leptin-dependent stimulation of FAO. As partial leptin deficiency is not uncommon in the general population, supplementation with BAIBA may help to prevent diet-induced obesity and related metabolic disorders in low leptin secretors.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The effects of long‐term physical inactivity on the expression of microRNAs involved in the regulation of skeletal muscle mass in humans are largely unknown. MicroRNAs are short, noncoding RNAs that ...fine‐tune target expression through mRNA degradation or by inhibiting protein translation. Intronic to the slow, type I, muscle fiber type genes MYH7 and MYH7b, microRNA‐208b and microRNA‐499‐5p are thought to fine‐tune the expression of genes important for muscle growth, such as myostatin. Spinal cord injured humans are characterized by both skeletal muscle atrophy and transformation toward fast‐twitch, type II fibers. We determined the expression of microRNA‐208b, microRNA‐499‐5p, and myostatin in human skeletal muscle after complete cervical spinal cord injury. We also determined whether these microRNAs altered myostatin expression in rodent skeletal muscle. A progressive decline in skeletal muscle microRNA‐208b and microRNA‐499‐5p expression occurred in humans during the first year after spinal cord injury and with long‐standing spinal cord injury. Expression of myostatin was inversely correlated with microRNA‐208b and microRNA‐499‐5p in human skeletal muscle after spinal cord injury. Overexpression of microRNA‐208b in intact mouse skeletal muscle decreased myostatin expression, whereas microRNA‐499‐5p was without effect. In conclusion, we provide evidence for an inverse relationship between expression of microRNA‐208b and its previously validated target myostatin in humans with severe skeletal muscle atrophy. Moreover, we provide direct evidence that microRNA‐208b overexpression decreases myostatin gene expression in intact rodent muscle. Our results implicate that microRNA‐208b modulates myostatin expression and this may play a role in the regulation of skeletal muscle mass following spinal cord injury.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•Proteome analysis using 2-D DIGE on cultured myotubes from T2D patients was performed.•Differentially abundant proteins involved in energy metabolism and oxidative stress are elevated in myotubes ...derived from T2D patients versus NGT individuals.•An altered profile of proteins is associated with protein dynamics and gene regulation in myotubes derived from T2D patients.
The development of insulin resistance and type 2 diabetes (T2D) involves a complex array of metabolic defects in skeletal muscle. An in vitro cell culture system excludes the acute effects of external systemic factors existing in vivo. Thus, we aimed to determine whether intrinsic differences in the protein profile exist in cultured myotubes derived from T2D versus normal glucose tolerant (NGT) healthy people. Applying two dimensional difference gel electrophoresis technology (2-D DIGE), the abundance of 47 proteins differed in myotubes derived from T2D patients versus NGT donors. Proteins involved in fatty acid and amino acid metabolism, TCA cycle, mitochondrial function, mRNA processing, DNA repair and cell survival showed higher abundance, while proteins associated with redox signaling (PARK7; Parkinson disease 7), glutathione metabolism (glutathione S-transferase, GST, isoforms T1, P1 and M2), and protein dynamics (heat shock protein, HSP, isoform B1 and 90A) showed reduced abundance in myotubes derived from T2D versus NGT donors. Consistent with our proteome analysis results, the level of total glutathione was reduced in myotubes obtained from T2D versus NGT donors. Taken together, our data provide evidence for intrinsic differences in the profile of proteins involved in energy metabolism, cellular oxidative stress, protein dynamics and gene regulation in myotubes derived from T2D patients. These differences thereby suggest a genetic or epigenetic influence on protein content level, which can be further investigated to understand the molecular underpinnings of T2D progression and lead to new therapeutic approaches.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Calorie-enriched diet and lack of work out are causing a worldwide surge of obesity and insulin resistance (IR), which favors lipid accretion in the liver (i.e. hepatic steatosis, or fatty liver). ...Indeed, IR in the adipose tissue increases lipolysis and the entry of free fatty acids (FFAs) in the liver, whereas IR-associated hyperinsulinemia favors
de novo synthesis of FFAs and triacylglycerol (TAG) molecules (i.e. lipogenesis). Fortunately, some hormonal and metabolic adaptations are set up to restrain fat accumulation in the liver, such as an increase in fatty acid oxidation (FAO). Although fatty liver is a benign condition in majority of patients, it can develop in some individuals into nonalcoholic steatohepatitis (NASH), which can further evolve into cirrhosis. Currently, the mechanisms responsible for this progression are still poorly understood but could involve the overproduction of reactive oxygen species (ROS) and a large array of deleterious cytokines that promote cell death, inflammation and fibrosis. Importantly, mitochondria appear to be a major site of ROS generation within the hepatocytes during NASH, which could be related to lower glutathione (GSH) import in these organelles, increased local expression of cytochrome P450 2E1 (CYP2E1) and enhanced leakage of electrons from the mitochondrial respiratory chain (MRC) caused by boosted FAO and concomitant MRC impairment. A vicious circle can ensue because ROS can damage the mitochondrial DNA and key components of the MRC, thus further impairing the MRC and augmenting electron leakage and ROS formation. In theory, the ideal drug for the treatment of NASH would reduce fat accretion in the liver and decrease cytokine and ROS overproduction. Although this drug does not exist at the moment, there are some synthetic and natural derivatives presenting metabolic and/or antioxidative effects that can directly or indirectly improve mitochondrial function during NASH.
Michael N. Sack and Paul M. Hwang – National Heart Lung and Blood Institute, National Institute of Health, Bethesda, MD, USA
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Calorie-enriched diet and lack of work out are causing a worldwide surge of obesity and insulin resistance (IR), which favors lipid accretion in the liver (i.e. hepatic steatosis, or fatty liver). ...Indeed, IR in the adipose tissue increases lipolysis and the entry of free fatty acids (FFAs) in the liver, whereas IR-associated hyperinsulinemia favors de novo synthesis of FFAs and triacylglycerol (TAG) molecules (i.e. lipogenesis). Fortunately, some hormonal and metabolic adaptations are set up to restrain fat accumulation in the liver, such as an increase in fatty acid oxidation (FAO). Although fatty liver is a benign condition in majority of patients, it can develop in some individuals into nonalcoholicsteatohepatitis (NASH), which can further evolve into cirrhosis. Currently, the mechanisms responsible for this progression are still poorly understood but could involve the overproduction of reactive oxygen species (ROS) and a large array of deleterious cytokines that promote cell death, inflammation and fibrosis. Importantly, mitochondria appear to be a major site of ROS generation within the hepatocytes during NASH, which could be related to lower glutathione (GSH) import in these organelles, increased local expression of cytochrome P450 2E1 (CYP2E1) and enhanced leakage of electrons from the mitochondrial respiratory chain (MRC) caused by boosted FAO and concomitant MRC impairment. A vicious circle can ensue because ROS can damage the mitochondrial DNA and key components of the MRC, thus further impairing the MRC and augmenting electron leakage and ROS formation. In theory, the ideal drug for the treatment of NASH would reduce fat accretion in the liver and decrease cytokine and ROS overproduction. Although this drug does not exist at the moment, there are some synthetic and natural derivatives presenting metabolic and/or antioxidative effects that can directly or indirectly improve mitochondrial function during NASH.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Reaching a beneficial intestinal microbiota early in life is desirable for piglets, as microbiota will impact their future health. One strategy to achieve this is the addition of prebiotics to sows' ...diet, as their microbiota will be transferred. Transmission of microbiota to the offspring occurs at birth and during lactation but a transfer might also occur during gestation. The objectives of this study were to determine whether and when (before and/or after birth) a maternal transfer of the microbiota occurs, and to observe the impact of wheat bran (WB) in sows' diet on their faecal microbiota, their offspring's microbiota and fermentation profile. Sequencing was performed on DNA extracted from umbilical cord blood, meconium, sows' faeces and piglets' colon content. Short-chain fatty acid production was determined in piglets' distal gut. Different bacteria (mostly Proteobacteria, followed by Firmicutes) were found in the umbilical cord blood, suggesting a maternal transfer occurring already during gestation. Less butyrate was produced in the caecum of WB piglets and a lower concentration of valerate was observed in all intestinal parts of WB piglets. Maternal wheat bran supplementation affected microbiota of sows and piglets differently.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Establishment of a beneficial microbiota profile for piglets as early in life as possible is important as it will impact their future health. In the current study, we hypothesized that resistant ...starch (RS) provided in the maternal diet during gestation and lactation will be fermented in their hindgut, which would favourably modify their milk and/or gut microbiota composition and that it would in turn affect piglets' microbiota profile and their absorptive and immune abilities.
In this experiment, 33% of pea starch was used in the diet of gestating and lactating sows and compared to control sows. Their faecal microbiota and milk composition were determined and the colonic microbiota, short-chain fatty acids (SCFA) production and gut health related parameters of the piglets were measured two days before weaning. In addition, their overall performances and post-weaning faecal score were also assessed.
The RS diet modulated the faecal microbiota of the sows during gestation, increasing the Firmicutes:Bacteroidetes ratio and the relative abundance of beneficial genera like Bifidobacterium but these differences disappeared during lactation and maternal diets did not impact the colonic microbiota of their progeny. Milk protein concentration decreased with RS diet and lactose concentration increased within the first weeks of lactation while decreased the week before weaning with the RS diet. No effect of the dietary treatment, on piglets' bodyweight or diarrhoea frequency post-weaning was observed. Moreover, the intestinal morphology measured as villus height and crypt depths, and the inflammatory cytokines in the intestine of the piglets were not differentially expressed between maternal treatments. Only zonula occludens 1 (ZO-1) was more expressed in the ileum of piglets born from RS sows, suggesting a better closure of the mucosa tight junctions.
Changes in the microbiota transferred from mother to piglets due to the inclusion of RS in the maternal diet are rather limited even though milk composition was affected.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the past several years, the use of resistant starch (RS) as prebiotic has extensively been studied in pigs, and this mostly in the critical period around weaning. RS is believed to exert ...beneficial effects on the gastrointestinal tract mainly due to higher levels of short chain fatty acids (SCFAs) and an improved microbiota profile. In this study, sows were fed digestible starch (DS) or RS during late gestation and lactation and the possible maternal effect of RS on the overall health of the progeny was assessed. Since RS is also described to have a positive effect on metabolism, and to investigate a metabolic programming of the progeny, half of the piglets per maternal diet were assigned to a high fat diet from weaning on to 10 weeks after.
No bodyweight differences were found between the four experimental piglet groups. The high fat diet did however impact back fat thickness and meat percentage whereas maternal diet did not influence these parameters. The impact of the high fat diet was also reflected in higher levels of serum cholesterol. No major differences in microbiota could be distinguished, although higher levels of SCFA were seen in the colon of piglets born from RS fed sows, and some differences in SCFA production were observed in the caecum, mainly due to piglet diet. RNA-sequencing on liver and colon scrapings revealed minor differences between the maternal diet groups. Merely a handful of genes was differentially expressed between piglets from DS and RS sows, and network analysis showed only one significant cluster of genes in the liver due to the maternal diet that did not point to meaningful biological pathways. However, the high fat diet resulted in liver gene clusters that were significantly correlated with piglet diet, of which one is annotated for lipid metabolic processes. These clusters were not correlated with maternal diet.
There is only a minor impact of maternal dietary RS on the progeny, reflected in SCFA changes. A high fat diet given to the progeny directly evokes metabolic changes in the liver, without any maternal programming by a RS diet.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cet ouvrage documente et analyse une expérimentation de recherche en sciences sociales menée en Afrique de l’Ouest au sein d’une Organisation Non-Gouvernementale Internationale de développement ...centrée sur l’enfance – Plan-International. L’histoire de cette aventure explore des questions cruciales : recherche et intervention sont-elles conciliables ? Comment associer des enfants à la recherche ? Quel est leur intérêt à en être ? Avec quelles conséquences ? Cette expérimentation avec les enfants oscille entre la recherche participative et collaborative. Les auteurs défendent le grand intérêt de l’association avec des artistes. Ils indiquent des voies, recommandent des postures, et soulignent les divers effets, les limites ainsi que les défis des techniques d’expression adoptées. L’ouvrage est non seulement une invitation à l’expérimentation permanente et à l’intégration de la recherche dans les institutions d’intervention en faveur de l’enfance comme mode d’action auprès de leurs publics, ainsi qu’une source d’adaptation continue ; il présente aussi des usages de la recherche par les enfants et les jeunes. On y découvre comment ils parviennent à se créer des espaces politiques et des positionnements à travers la curiosité, l’art – notamment le rap – et le débat. Ancrés dans la pratique, les divers exemples et documents issus de cette expérimentation présentés ici témoignent de la sensibilité des chercheurs/ethnographes qui ont réalisé les travaux et de la générosité de leurs interlocuteurs. Ces traces, des photographies et des extraits d’échanges et de performances, proposent une identité générationnelle ouest-africaine forte : des jeunes et des enfants réalistes et dynamiques.
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