June 2018
·
16 Reads
This page lists the scientific contributions of an author, who either does not have a ResearchGate profile, or has not yet added these contributions to their profile.
It was automatically created by ResearchGate to create a record of this author's body of work. We create such pages to advance our goal of creating and maintaining the most comprehensive scientific repository possible. In doing so, we process publicly available (personal) data relating to the author as a member of the scientific community.
If you're a ResearchGate member, you can follow this page to keep up with this author's work.
If you are this author, and you don't want us to display this page anymore, please let us know.
June 2018
·
16 Reads
June 2018
·
17 Reads
June 2018
·
18 Reads
May 2018
·
242 Reads
·
21 Citations
The FASEB Journal
Postnatal overfeeding increases the risk of chronic diseases later in life, including obesity, insulin resistance, hepatic steatosis, and type 2 diabetes. Epigenetic mechanisms might underlie the long-lasting effects associated with early nutrition. Here we aimed to explore the molecular pathways involved in early development of insulin resistance and hepatic steatosis, and we examined the potential contribution of DNA methylation and histone modifications to long-term programming of metabolic disease. We used a well-characterized mouse model of neonatal overfeeding and early adiposity by litter size reduction. Neonatal overfeeding led to hepatic insulin resistance very early in life that persisted throughout adulthood despite normalizing food intake. Up-regulation of monoacylglycerol O-acyltransferase ( Mogat) 1 conceivably mediates hepatic steatosis and insulin resistance through increasing intracellular diacylglycerol content. Early and sustained deregulation of Mogat1 was associated with a combination of histone modifications that might favor Mogat1 expression. In sum, postnatal overfeeding causes extremely rapid derangements of hepatic insulin sensitivity that remain relatively stable until adulthood. Epigenetic mechanisms, particularly histone modifications, could contribute to such long-lasting effects. Our data suggest that targeting hepatic monoacylglycerol acyltransferase activity during early life might provide a novel strategy to improve hepatic insulin sensitivity and prevent late-onset insulin resistance and fatty liver disease.-Ramon-Krauel, M., Pentinat, T., Bloks, V. W., Cebrià, J., Ribo, S., Pérez-Wienese, R., Vilà, M., Palacios-Marin, I., Fernández-Pérez, A., Vallejo, M., Téllez, N., Rodríguez, M. À., Yanes, O., Lerin, C., Díaz, R., Plosch, T., Tietge, U. J. F., Jimenez-Chillaron, J. C. Epigenetic programming at the Mogat1 locus may link neonatal overnutrition with long-term hepatic steatosis and insulin resistance.
June 2016
·
39 Reads
May 2014
·
315 Reads
·
26 Citations
FATP1 mediates skeletal muscle cell fatty acid import, yet its intracellular localization and metabolic control role are not completely defined. Here, we examine FATP1 localization and metabolic effects of its overexpression in mouse skeletal muscle. The FATP1 protein was detected in mitochondrial and plasma membrane fractions, obtained by differential centrifugation, of mouse gastrocnemius muscle. FATP1 was most abundant in purified mitochondria, and in the outer membrane and soluble intermembrane, but not in the inner membrane plus matrix, enriched subfractions of purified mitochondria. Immunogold electron microscopy localized FATP1-GFP in mitochondria of transfected C2C12 myotubes. FATP1 was overexpressed in gastrocnemius mouse muscle, by adenovirus-mediated delivery of the gene into hindlimb muscles of newborn mice, fed after weaning a chow or high-fat diet. Compared to GFP delivery, FATP1 did not alter body weight, serum fed glucose, insulin and triglyceride levels, and whole-body glucose tolerance, in either diet. However, fatty acid levels were lower and β-hydroxybutyrate levels were higher in FATP1- than GFP-mice, irrespective of diet. Moreover, intramuscular triglyceride content was lower in FATP1- versus GFP-mice regardless of diet, and β-hydroxybutyrate content was unchanged in high-fat-fed mice. Electroporation-mediated FATP1 overexpression enhanced palmitate oxidation to CO2, but not to acid-soluble intermediate metabolites, while CO2 production from β-hydroxybutyrate was inhibited and that from glucose unchanged, in isolated mouse gastrocnemius strips. In summary, FATP1 was localized in mitochondria, in the outer membrane and intermembrane parts, of mouse skeletal muscle, what may be crucial for its metabolic effects. Overexpressed FATP1 enhanced disposal of both systemic fatty acids and intramuscular triglycerides. Consistently, it did not contribute to the high-fat diet-induced metabolic dysregulation. However, FATP1 lead to hyperketonemia, likely secondary to the sparing of ketone body oxidation by the enhanced oxidation of fatty acids.
April 2014
·
109 Reads
·
169 Citations
Cell Metabolism
Obesity and type 2 diabetes have a heritable component that is not attributable to genetic factors. Instead, epigenetic mechanisms may play a role. We have developed a mouse model of intrauterine growth restriction (IUGR) by in utero malnutrition. IUGR mice developed obesity and glucose intolerance with aging. Strikingly, offspring of IUGR male mice also developed glucose intolerance. Here, we show that in utero malnutrition of F1 males influenced the expression of lipogenic genes in livers of F2 mice, partly due to altered expression of Lxra. In turn, Lxra expression is attributed to altered DNA methylation of its 5' UTR region. We found the same epigenetic signature in the sperm of their progenitors, F1 males. Our data indicate that in utero malnutrition results in epigenetic modifications in germ cells (F1) that are subsequently transmitted and maintained in somatic cells of the F2, thereby influencing health and disease risk of the offspring.
July 2012
·
498 Reads
·
243 Citations
Biochimie
Nutrition plays a key role in many aspects of health and dietary imbalances are major determinants of chronic diseases including cardiovascular disease, obesity, diabetes and cancer. Adequate nutrition is particularly essential during critical periods in early life (both pre- and postnatal). In this regard, there is extensive epidemiologic and experimental data showing that early sub-optimal nutrition can have health consequences several decades later. The hypothesis that epigenetic mechanisms may link such nutritional imbalances with altered disease risk has been gaining acceptance over recent years. Epigenetics can be defined as the study of heritable changes in gene expression that do not involve alterations in the DNA sequence. Epigenetic marks include DNA methylation, histone modifications and a variety of non-coding RNAs. Strikingly, they are plastic and respond to environmental signals, including diet. Here we will review how dietary factors modulate the establishment and maintenance of epigenetic marks, thereby influencing gene expression and, hence, disease risk and health.
October 2010
·
99 Reads
·
137 Citations
Endocrinology
Epidemiological and clinical data show that rapid weight gain early in life is strongly associated with several components of the metabolic syndrome. Strikingly, abnormal growth rates in early life can additionally influence diabetes risk in subsequent generations. Here we aim to study whether neonatal overgrowth induces diabetes in offspring and grand-offspring of affected individuals using a mouse model of neonatal overfeeding. We induced neonatal overgrowth (ON-F0) by culling offspring to four pups per dam during lactation. By age 4 months, ON-F0 mice developed many features of the metabolic syndrome, including obesity, insulin resistance, and glucose intolerance. We then studied whether male offspring (ON-F1) and grand-offspring (ON-F2) of ON-F0 male mice, which were not overfed during lactation, developed features of the metabolic syndrome with aging. ON-F1 mice developed fed and fasting hyperinsulimemia, hypertryglyceridemia, insulin resistance, and glucose intolerance, but not obesity, by age 4 months. In contrast, ON-F2 male mice showed a more moderate phenotype and only developed fasting hyperglycemia and glucose intolerance by age 4 months. Impaired glucose tolerance in ON-F1 and ON-F2 mice appeared to be accounted for primarily by peripheral insulin resistance, because beta-cell function remained normal or even increased in these cohorts. Nutritional challenges occurring during sensitive periods of development may have adverse metabolic consequences well beyond the lifespan of affected individuals and manifest in subsequent generations. Transgenerational progression of metabolic phenotypes through the male lineage supports a potential role for epigenetic mechanisms in mediating these effects.
February 2009
·
5 Reads
... As discussed in the text, the relationship between litter size and the reported physiological variables is complex and does not necessarily follow a simple linear correlation. Data included in these graphs include unpublished results as well as data partially published in two independent articles [18,44]. Data represent the mean values AE Standard error mean. ...
May 2018
The FASEB Journal
... CD36, cluster of differentiation 36/SR-B3 (previously SR-B2); CPT1, carnitine palmitoyltransferase 1; CPT2, carnitine palmitoyltransferase 2; FABPpm, fatty acid binding protein plasma membrane, plasma membrane; FATP1, fatty acid transport protein 1; FATP4, fatty acid transport protein 4, FATP4; TCA, tricarboxylic acid. We acknowledge that the specific localisation of FATP1 is debated [14,15,48] Sandy, UT, USA), and the last minute at each power output was used to estimate whole-body carbohydrate (CHO) and fatty acid oxidation rates, and energy expenditure, using standard non-protein stoichiometric equations [24]. The PFO was identified as having the highest observed rate of wholebody fatty acid oxidation during the incremental cycling test [1]. ...
May 2014
... Similarly, there is evidence of maternally inherited histone mark H3K27me3 in F1 offspring of Drosophila [77]. Furthermore, the inheritance of metabolic phenotypes via transmission of DNA methylation marks [39,53] and small regulatory RNA species [16] to offspring has also been documented. Thus, environmental challenges including high energy diet could alter epigenetic signatures and program embryo development. ...
April 2014
Cell Metabolism
... Por exemplo, exposições paternas a produtos químicos carcinógenos, consumo excessivo de gorduras trans, estresse e outros fatores também estão relacionados a discussões sobre herança epigenética transgeracional. (Li, 2013;Jimenez-Chillaron, 2012) Existe uma grande quantidade de produtos químicos desreguladores endócrinos, incluindo uma amplas categorias de medicamentos, produtos químicos, aditivos alimentares e substâncias em muitos produtos de uso doméstico. Alguns estudos indicam que a frequente exposição aos produtos químicos desreguladores endócrinos podem se estender a várias gerações e aumentar o risco de doenças em humanos. ...
July 2012
Biochimie
... The observed lack of significant differences in the body weight of offspring is similar to a previous study in mammals where the body weight of WR-fed rat offspring did not differ from the control despite disrupted metabolism [28]. A similar finding was reported in a mouse model where F1 offspring of diet challenged parent developed IR but not obesity [50]. It was also observed that HSD-fed control flies did not exhibit any statistically significant differences in weight and this is not surprising because weight may not be an adequate metric of obesity in flies in the presence of other well established obesity features such as fat accumulation and reduced climbing ability [5]. ...
October 2010
Endocrinology
... Concerning the influence of maternal nutrition over generations, feeding of a poor nutritional diet in pregnant mice from E12.5 until birth results in inheritance of glucose intolerance in F1 as well as F2 generations through both male and female F1 parents [74]. Further study showed that maternal undernutrition during E12.5 to E18.5 causes locus-specific hypomethylation in intergenic regions and CGIs including regulatory elements as well as in nucleosome-retaining regions in adult F1 sperm [75]. ...
November 2008
Diabetes