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Mechanisms of thrifty protein-energy metabolism crosslinked with insulin resistance during catch-up growth - a risk factor for later obesity and metabolic syndrome

English title Mechanisms of thrifty protein-energy metabolism crosslinked with insulin resistance during catch-up growth - a risk factor for later obesity and metabolic syndrome
Applicant Dulloo Abdul G.
Number 152870
Funding scheme Project funding
Research institution Division de Physiologie Département de Médecine Université de Fribourg
Institution of higher education University of Fribourg - FR
Main discipline Physiology : other topics
Start/End 01.07.2014 - 31.12.2017
Approved amount 525'000.00
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Keywords (5)

Adaptive thermogenesis; Catch-up growth ; Low birth weight; Insulin resistance; Obesity

Lay Summary (French)

Lead
Contexte Les personnes nées avec un faible poids corporel ou dont la croissance corporelle est ralentie pendant l'enfance et qui, par la suite présentent un rattrapage de croissance, auront plus tard une plus grande susceptibilité à l'obésité, au diabète de type 2 et aux maladies cardio-vasculaires (les maladies du 'syndrome métabolique'). Ce projet apporte sa contribution à la compréhension des mécanismes par lesquels le rattrapage de croissance prédispose à ces maladies.
Lay summary
Contenu et objectifs du travail de recherche

A l’aide de notre modèle validé de rattrapage de croissance chez le rat - dans lequel le rattrapage de la masse grasse et la résistance à l’insuline de la musculature squelettique sont dirigés par la suppression de thermogenèse - notre recherche qui fait appel à des techniques de biologie moléculaire et de physiologie intégrative, se présente sous  3 projets :

1. Etude du rôle d’un ralentissement du turnover des protéines dans les mécanismes de diminution de thermogenèse liée à la résistance à l’insuline de la musculature squelettique lors de la réalimentation soit avec un régime pauvre en graisse ou avec un régime enrichi en graisse saturée.

2. Etude des mécanismes par lesquels un régime enrichi en acides gras polyinsaturés induit une accrétion des protéines et améliore l’homéostasie de la glycémie lors du rattrapage de croissance.

3. Tester chez le rat et dans une cohorte de jeunes adultes à l’aide de techniques télémétriques l’hypothèse selon laquelle une température corporelle abaissée constitue un trait d’épargne métabolique (énergétique-protéinique) lors du rattrapage de croissance et donc contribue à la diminution de thermogenèse responsable de l’accrétion de la masse grasse.  

Contexte scientifique et social du projet de recherche

Ce domaine de recherche est d'actualité en médecine clinique car le rattrapage de croissance est une phase critique favorisant le développement des maladies métaboliques et, de plus, peut exposer des jeunes enfants et des adolescents à des troubles métaboliques durant les périodes de croissance et de développement et, ainsi, les prédisposant aux maladies métaboliques chroniques.

 

 

Direct link to Lay Summary Last update: 27.05.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
Reduced Skeletal Muscle Protein Turnover and Thyroid Hormone Metabolism in Adaptive Thermogenesis That Facilitates Body Fat Recovery During Weight Regain.
CalonneJulie, IsaccoLaurie, Miles-ChanJennifer, ArsenijevicDenis, MontaniJean-Pierre, GuilletChristelle, BoirieYves, DullooAbdul (2019), Reduced Skeletal Muscle Protein Turnover and Thyroid Hormone Metabolism in Adaptive Thermogenesis That Facilitates Body Fat Recovery During Weight Regain., in Front Endocrinol, 10(119), 1-10.
Posture Allocation Revisited: Breaking the Sedentary Threshold of Energy Expenditure for Obesity Management.
Miles-ChanJennifer, DullooAbdul (2017), Posture Allocation Revisited: Breaking the Sedentary Threshold of Energy Expenditure for Obesity Management., in Front Physiol., 8, 1-11.
Collateral fattening: When a deficit in lean body mass drives overeating.
Dulloo AG (2017), Collateral fattening: When a deficit in lean body mass drives overeating., in Obesity (Silver Spring), 25(2), 277-279.
Isometric thermogenesis at rest and during movement: a neglected variable in energy expenditure and obesity predisposition
Dulloo AG, Miles-Chan JL, Montani JP, Schutz Y (2017), Isometric thermogenesis at rest and during movement: a neglected variable in energy expenditure and obesity predisposition, in Obes Rev. , 18(suppl 1), 56-64.
Issues in Continuous 24-h Core Body Temperature Monitoring in Humans Using an Ingestible Capsule Telemetric Sensor.
Monnard CR, Fares EJ, Calonne J ., Miles-Chan JL, Montani JP, Durrer D, Schutz Y, Dulloo AG (2017), Issues in Continuous 24-h Core Body Temperature Monitoring in Humans Using an Ingestible Capsule Telemetric Sensor., in Front Endocrinol , 13, 1-13.
Passive and active roles of fat-free mass in the control of energy intake and body composition regulation.
Dulloo AG, Jacquet J, Miles-Chan JL, Schutz Y (2017), Passive and active roles of fat-free mass in the control of energy intake and body composition regulation., in Eur J Clin Nutr, 71(3), 353-357.
Polyunsaturated Fatty Acids Stimulate De novo Lipogenesis and Improve Glucose Homeostasis during Refeeding with High Fat Diet.
Crescenzo R, Mazzoli A, Cancelliere R, Bianco F, Giacco A, Liverini G, Dulloo AG, Iossa S (2017), Polyunsaturated Fatty Acids Stimulate De novo Lipogenesis and Improve Glucose Homeostasis during Refeeding with High Fat Diet., in Front Physiol, 8(178), 1-9.
Reliability of low-power cycling efficiency in energy expenditure phenotyping of inactive men and women.
Fares EJ, Isacco L, Monnard CR, Miles-Chan JL, Montani JP, Schutz Y, Dulloo AG (2017), Reliability of low-power cycling efficiency in energy expenditure phenotyping of inactive men and women., in Physiol Rep, 5(9), 1-13.
Caloric restriction induces energy-sparing alterations in skeletal muscle contraction, fiber composition and local thyroid hormone metabolism that persist during catch-up fat upon refeeding.
De Andrade PA, Neff LA, Strosova MK, Arsenijevic D, Patthey-Vuadens O, Scapozza L, Montani JP, Ruegg UT, Dulloo AG, Dorchies OM (2015), Caloric restriction induces energy-sparing alterations in skeletal muscle contraction, fiber composition and local thyroid hormone metabolism that persist during catch-up fat upon refeeding., in Front Physiol , 6(254), 1-14.
De novo lipogenesis in metabolic homeostasis: More friend than foe?
Solinas G, Borén J, Dulloo AG (2015), De novo lipogenesis in metabolic homeostasis: More friend than foe?, in Mol metab, 4(5), 367-377.

Collaboration

Group / person Country
Types of collaboration
Professor Yves Boirie, Clermont-Ferrand (France) France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Françoise Rohner-Jeanrenaud, Centre Médical Universitaire de Genève Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
4th Recent Advances & Controversies in Measurement of Energy Metabolism Talk given at a conference Novel approaches in phenotyping human variability in thermogenesis 21.10.2017 Fribourg , Switzerland Dulloo Abdul G.;
4th Recent Advances & Controversies in Measurement of Energy Metabolism Talk given at a conference Low 24-hour core body temperature as a thrifty metabolic trait driving catch-up fat during weight regain after caloric restriction 21.09.2017 Fribourg, Switzerland Calonne Julie;
Conference of the Autonomous University of Baja California Talk given at a conference Does dieting and weight cycling make people fatter? 06.09.2017 Tijuana , Mexico Dulloo Abdul G.;
24th European Congress on Obesity Talk given at a conference Collateral fattening: when a deficit in lean body mass drives overeating 17.05.2017 Porto, Portugal Dulloo Abdul G.;
24th European Congress on Obesity Poster Reduced skeletal muscle protein turnover and deiodinase-3 upregulation in the adaptive thermogenesis that facilitates body fat recovery during weight regain. 17.05.2017 Porto, Portugal Calonne Julie;
29ème Journée de Nutrition Genevoise de Nutrition Clinique et Diétothérapie Talk given at a conference Le jeûne et l’après jeûne: biochimie et physiologie 23.03.2017 Geneva Hospital, Switzerland Dulloo Abdul G.;
11th Annual meeting of the Swiss Association for the Study of Obesity Talk given at a conference Metabolic adaptations contributing to weight regain: Clinical significance & molecular mechanisms 20.11.2016 Bern, Switzerland Dulloo Abdul G.;
International Symposium on Energy Balance Talk given at a conference Novel Perspectives into Research on Energy Balance 10.09.2016 Hohenheim, Germany Dulloo Abdul G.;
13th International Congress on Obesity Talk given at a conference Energy expenditure phenotyping during low physical activity levels: validation using low power cycling exercise in sedentary humans. 01.05.2016 Vancouver, Canada Fares Elie-Jacques;
13th International Congress on Obesity Poster A role for altered skeletal muscle deiodinases and local thyroid hormone metabolism in adaptive thermogenesis driving catch-up fat after caloric restriction. 01.05.2016 Vancouver, Canada Calonne Julie;


Associated projects

Number Title Start Funding scheme
176116 Phenotyping for thrifty metabolic traits in young adults born small: a risk factor for later obesity and cardiometabolic diseases 01.01.2018 Project funding
113634 Mechanisms underlying glucose redistribution from skeletal muscle to adipose tissue during catch-up growth - a determinant for later obesity and metabolic syndrome 01.10.2006 Project funding
176116 Phenotyping for thrifty metabolic traits in young adults born small: a risk factor for later obesity and cardiometabolic diseases 01.01.2018 Project funding
130481 Mechanisms of impaired glucose homeostasis during catch-up growth - a risk factor for later obesity and metabolic syndrome 01.07.2010 Project funding

Abstract

Background It is now well recognized that catch-up growth during infancy and childhood is a major risk factor for obesity, type 2 diabetes and cardiovascular diseases later in life. While catch-up growth per se is characterized as a state of hyperinsulinemia and a disproportionately higher rate of fat deposition relative to that of lean tissue (i.e. preferential catch-up fat), the mechanisms by which catch-up growth confers sensitivity towards these risks for later obesity and disease entities of the metabolic syndrome are still poorly understood. Working Hypothesis An enhanced metabolic efficiency for preferential catch-up fat, which is characterized by a thrifty energy metabolism crosslinked with skeletal muscle insulin resistance, confers to the phase of catch-up growth its predisposition towards the development of impaired glucose tolerance. Aims To elucidate the thermogenic effector system(s) whose downregulation underlies the thrifty energy metabolism that crosslinks with skeletal muscle insulin resistance. Design Using primarily a validated rat model of catch-up growth in which catch-up fat and skeletal muscle insulin resistance are driven by suppressed thermogenesis per se (and not hyperphagia), our research merges techniques of molecular biology and integrative physiology, to investigate the following:• In Project I, investigations will focus on the potential role of diminished skeletal muscle protein turnover (an energy costly substrate cycle) and its links with insulin resistance in the mechanisms that suppress thermogenesis favouring catch-up fat during refeeding on a low-fat diet, and its exacerbation by high-fat diets. The central hypothesis to be tested is that the insulin resistance in skeletal muscle involves not only impairments in glucose uptake/utilization but also impairments in protein metabolism, resulting in diminished protein turnover which contributes to suppress thermogenesis. • In Project II, the studies will investigate the extent to which in-vivo insulin-stimulated glucose and protein metabolism in skeletal muscle and adipose tissue are altered by diets high in essential (polyunsaturated) fatty acids, which we previously reported to be effective in enhancing energy partitioning to lean tissues, thereby countering the exacerbating effect of high-fat diets on catch-up fat and hyperinsulinemia. • In Project III, we will test the hypothesis that a thrifty metabolic trait could also reside in a lower core body temperature by conducting studies involving 24h telemetry for assessing core temperature and locomotor activity (i) in our rat model of catch-up fat and (ii) in a cohort of young healthy men and women. Significance These studies will help to elucidate the physio(patho)logical mechanisms by which the efficient metabolism that drives fat storage after periods of slower growth confers to the phase of subsequent catch-up growth its increased sensitivity towards development of chronic diseases centered upon the insulin resistance (metabolic) syndrome. This area has special clinical relevance since catch-up growth can last for several years in humans, thereby exposing infants and children to the potentially damaging metabolic insults during critical periods of growth and development, and hence predisposing them towards chronic metabolic diseases.
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