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Phenotyping for thrifty metabolic traits in young adults born small: a risk factor for later obesity and cardiometabolic diseases

English title Phenotyping for thrifty metabolic traits in young adults born small: a risk factor for later obesity and cardiometabolic diseases
Applicant Dulloo Abdul G.
Number 176116
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 01.01.2018 - 31.07.2020
Approved amount 457'495.00
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Keywords (5)

Low birth weight; Catch-up growth ; Insulin resistance; Adaptive thermogenesis; 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').
Lay summary

Contenu et objectifs du travail de recherche
Ce projet cherche à savoir dans quelle mesure les adultes jeunes et sains ayant eu un faible poids à la naissance présentent des caractéristiques d’économie énergétique. En effet ces adaptations métaboliques pourraient favoriser le développement de l’obésité  dû à une diminution de la capacité de brûler les calories (au repos, en réponse à une boisson sucrée et un repas modérément riche en protéines, et lors d’exercices physiques de faible intensité), ainsi qu’à une température corporelle diminuée. Cette étude nous permettra de répondre aux principales questions suivantes :

  • Les jeunes adultes nés avec un faible poids corporel ont-ils une dépense énergétique diminuée ?

  • En réponse à la nourriture (glucose, protéine) ou lors d’activités physiques quotidiennes, est-ce que ces jeunes adultes diffèrent de ceux qui sont nés avec un poids corporel normal en ce qui concerne leur dépense énergétique et leurs fonctions cardiovasculaires?

  • La température centrale est-elle plus basse chez ces jeunes adultes avec un petit poids de naissance que chez ceux nés avec un poids normal ?

Contexte scientifique et social du projet de recherche
Cette étude constitue un enjeu essentiel dans la compréhension des mécanismes par lesquels les personnes nées avec un faible poids de naissance présentent une plus grande susceptibilité à développer obésité ainsi que des maladies cardio-vasculaires. Ce projet de recherche apportera de nouvelles connaissances et contribuera au développement d’approches plus précises en vue d’identifier les personnes les plus sujettes à l’obésité et aux maladies cardio-métaboliques associées. Ce projet permettra également de concevoir des stratégies d’intervention qui apporteront des avantages pour la santé à long terme tout en prévenant des effets néfastes.


Direct link to Lay Summary Last update: 13.12.2017

Responsible applicant and co-applicants

Employees

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Joint European and International Congress on Obesity (ECO-ICO 2020), Talk given at a conference Low-level physical activity: impact on weight regulation and cardiometabolic risks 17.05.2020 Dublin (Virtual conference), Ireland Dulloo Abdul G.;
Symposium d’Obésité Pédiatrique Talk given at a conference The thrifty catch-up fat phenotype in growth trajectories to obesity and cardiometabolic diseases 10.10.2019 Centre Hospitalier Universitaire Vaudois (CHUV), Switzerland Dulloo Abdul G.;
UNIL/CHUV-UNIFR meeting Talk given at a conference Issues in continuous 24-h core body temperature monitoring using an ingestible capsule telemetric sensor 07.05.2019 CHUV Lausanne, Switzerland Monnard Cathriona;


Self-organised

Title Date Place
Diet and Pathogenesis of Obesity & Cardiometabolic diseases 25.09.2018 University of Fribourg, Switzerland

Associated projects

Number Title Start Funding scheme
152870 Mechanisms of thrifty protein-energy metabolism crosslinked with insulin resistance during catch-up growth - a risk factor for later obesity and metabolic syndrome 01.07.2014 Project funding
152870 Mechanisms of thrifty protein-energy metabolism crosslinked with insulin resistance during catch-up growth - a risk factor for later obesity and metabolic syndrome 01.07.2014 Project funding

Abstract

Background: Large epidemiological and clinical studies suggest that people with low birth weight (LBW) - a reflection of fetal growth constraint most often followed by post-natal catch-up growth - have higher susceptibility for obesity, type 2 diabetes and cardiovascular diseases later in adult life. The mechanisms by which such early growth patterns confer predisposition to obesity and insulin-related diseases is unclear, amid theories of fetal and neonatal programming for a thrifty (energy conservation) phenotype. While perturbations in glucose homeostasis and diminished insulin sensitivity (a hallmark of cardiometabolic risks) have been well documented in infants, children and adults born small, the existence of thrifty metabolic traits still remains to be demonstrated in humans with LBW.Working Hypothesis, Rationale & Objective: Our working hypothesis is that it is the thrifty mechanisms that underlie the phenomenon of preferential catch-up fat - i.e. accelerated body fat storage during catch-up growth - that are ‘imprinted’ during early growth perturbations, and which operate in adulthood to confer increased risks for obesity and cardiometabolic diseases. Our objective is to phenotype, in human adults born with LBW, thrifty metabolic traits which we postulate on the basis of evidence we have obtained in a rat model of thrifty metabolism driving catch-up fat - namely the in-vivo demonstration of (i) diminished skeletal muscle glucose utilization - which can translate to diminished glucose-induced thermogenesis; (ii) diminished skeletal muscle protein turnover (an energetically costly substrate cycle) - which can translate to diminished protein-induced thermogenesis; (iii) diminished skeletal muscle contractile properties - which can translate to reduced energy cost of muscular work; and (iv) diminished core body temperature - an homeostatic mechanism which can translate to whole-body energy conservation. Design & Methods By merging techniques of indirect calorimetry, novel approaches for energy expenditure phenotyping during low-level physical activity and continuous core body temperature monitoring by ingestible capsule telemetric sensors to compare young healthy adults with LBW (range 1.5 - 2.5 kg) and those of normal birth weight (range 2.51 - 3.5 kg), we plan to test the hypotheses that thrifty metabolic traits in humans with LBW reside in the following: (i) in diminished postprandial thermogenesis in response to glucose assessed during an oral glucose tolerance test, (ii) in diminished postprandial thermogenesis in response to a high-protein meal, (iii) in a lower energy cost of light physical activities - during standing postural maintenance, dynamic (leg cycling) exercise at low power outputs, and during intermittent low-intensity isometric (leg press) exercise, and (iv) in a lower core body temperature, particularly in the post-absorptive state and during an acute cold water drink challenge. Significance The study here, centered upon the application of classic and novel approaches to phenotype potential thrifty metabolic traits, is an essential step towards defining the mechanisms by which humans born small may express an increased susceptibility to obesity and cardiometabolic diseases. Such research will advance knowledge and contribute towards the development of more refined approaches for identifying individuals most prone to obesity and associated cardiometabolic risks, and in the design of intervention strategies that would confer advantages for long-term health while preventing adverse health outcomes.
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