Carles Lerin

Bio: Carles Lerin is an academic researcher from Boston Children's Hospital. The author has contributed to research in topics: Medicine & Breast milk. The author has an hindex of 11, co-authored 21 publications receiving 8087 citations. Previous affiliations of Carles Lerin include Johns Hopkins University School of Medicine & University of Barcelona.

Resveratrol improves health and survival of mice on a high-calorie diet

Abstract: Resveratrol (3,5,49-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-c coactivator 1a (PGC-1a) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing.

eRah: A Computational Tool Integrating Spectral Deconvolution and Alignment with Quantification and Identification of Metabolites in GC/MS-Based Metabolomics

Abstract: Gas chromatography coupled to mass spectrometry (GC/MS) has been a long-standing approach used for identifying small molecules due to the highly reproducible ionization process of electron impact ionization (EI). However, the use of GC-EI MS in untargeted metabolomics produces large and complex data sets characterized by coeluting compounds and extensive fragmentation of molecular ions caused by the hard electron ionization. In order to identify and extract quantitative information on metabolites across multiple biological samples, integrated computational workflows for data processing are needed. Here we introduce eRah, a free computational tool written in the open language R composed of five core functions: (i) noise filtering and baseline removal of GC/MS chromatograms, (ii) an innovative compound deconvolution process using multivariate analysis techniques based on compound match by local covariance (CMLC) and orthogonal signal deconvolution (OSD), (iii) alignment of mass spectra across samples, (iv) ...

Metabolomics approach for analyzing the effects of exercise in subjects with type 1 diabetes mellitus.

Abstract: The beneficial effects of exercise in patients with type 1 diabetes (T1D) are not fully proven, given that it may occasionally induce acute metabolic disturbances. Indeed, the metabolic disturbances associated with sustained exercise may lead to worsening control unless great care is taken to adjust carbohydrate intake and insulin dosage. In this work, pre- and post-exercise metabolites were analyzed using a 1H-NMR and GC-MS untargeted metabolomics approach assayed in serum. We studied ten men with T1D and eleven controls matched for age, body mass index, body fat composition, and cardiorespiratory capacity, participated in the study. The participants performed 30 minutes of exercise on a cycle-ergometer at 80% VO2max. In response to exercise, both groups had increased concentrations of gluconeogenic precursors (alanine and lactate) and tricarboxylic acid cycle intermediates (citrate, malate, fumarate and succinate). The T1D group, however, showed attenuation in the response of these metabolites to exercise. Conversely to T1D, the control group also presented increases in α-ketoglutarate, alpha-ketoisocaproic acid, and lipolysis products (glycerol and oleic and linoleic acids), as well as a reduction in branched chain amino acids (valine and leucine) determinations. The T1D patients presented a blunted metabolic response to acute exercise as compared to controls. This attenuated response may interfere in the healthy performance or fitness of T1D patients, something that further studies should elucidate.

Dose translation from animal to human studies revisited

Abstract: As new drugs are developed, it is essential to appropriately translate the drug dosage from one animal species to another. A misunderstanding appears to exist regarding the appropriate method for allometric dose translations, especially when starting new animal or clinical studies. The need for education regarding appropriate translation is evident from the media response regarding some recent studies where authors have shown that resveratrol, a compound found in grapes and red wine, improves the health and life span of mice. Immediately after the online publication of these papers, the scientific community and popular press voiced concerns regarding the relevance of the dose of resveratrol used by the authors. The animal dose should not be extrapolated to a human equivalent dose (HED) by a simple conversion based on body weight, as was reported. For the more appropriate conversion of drug doses from animal studies to human studies, we suggest using the body surface area (BSA) normalization method. BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function. We advocate the use of BSA as a factor when converting a dose for translation from animals to humans, especially for phase I and phase II clinical trials.

Resveratrol improves health and survival of mice on a high-calorie diet

Abstract: Resveratrol (3,5,49-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-c coactivator 1a (PGC-1a) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing.

AMPK: a nutrient and energy sensor that maintains energy homeostasis

Abstract: AMP-activated protein kinase (AMPK) is a crucial cellular energy sensor. Once activated by falling energy status, it promotes ATP production by increasing the activity or expression of proteins involved in catabolism while conserving ATP by switching off biosynthetic pathways. AMPK also regulates metabolic energy balance at the whole-body level. For example, it mediates the effects of agents acting on the hypothalamus that promote feeding and entrains circadian rhythms of metabolism and feeding behaviour. Finally, recent studies reveal that AMPK conserves ATP levels through the regulation of processes other than metabolism, such as the cell cycle and neuronal membrane excitability.