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Mechanisms underlying glucose redistribution from skeletal muscle to adipose tissue during catch-up growth - a determinant for later obesity and metabolic syndrome

English title Mechanisms underlying glucose redistribution from skeletal muscle to adipose tissue during catch-up growth - a determinant for later obesity and metabolic syndrome
Applicant Dulloo Abdul G.
Number 113634
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 Endocrinology
Start/End 01.10.2006 - 30.06.2010
Approved amount 335'190.00
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Keywords (5)

adaptive thermogenesis; catch-up growth; obesity; low birth weight; insulin resistance

Lay Summary (English)

Lead
Lay summary
It has long been known that obesity, and in particular excess fat deposition in the abdominal region, is a high risk factor for resistance to the actions of insulin (insulin resistance), high blood levels of insulin (hyperinsulinemia), type 2 diabetes, and cardiovascular diseases - i.e. complications that are components of the ‘metabolic syndrome’. In more recent years, there has been compelling evidence suggesting that a pattern of poor growth followed by catch-up growth during infancy and childhood is also a major determinant for abdominal obesity, type 2 diabetes and cardiovascular diseases later in life. Although the process of catch-up growth per se is associated with hyperinsulinemia and an accelerated rate for body fat deposition (i.e. catch-up fat), the mechanisms by which catch-up growth confers sensitivity towards these risks for later obesity and metabolic syndrome are poorly understood. Our hypothesis is that an efficient (energy conserving) metabolism, resulting in glucose that is not oxidized in skeletal muscle being diverted for lipid synthesis in adipose tissue - confers to the phase of catch-up growth its sensitivity towards the development of insulin resistance andhyperinsulinemia.

Our aims are to elucidate the ‘push and pull’ mechanisms that underlie such redistribution of glucose from skeletal muscle towards adipose tissue, and how these mechanisms that underlie catch-up fat on a low-fat diet turns deleterious during catch-up growth on a typical contemporary diet high in saturated fat. Using a validated rat model of catch-up growth in which skeletal muscle insulin resistance has been linked to this efficient metabolism for catch-up fat, our research merges techniques of molecular biology, mitochondrial energetics and tissue fatty acid composition analysis to investigate :
(a) the mechanisms that constitute the efficient metabolism which results in reduced glucose oxidation in skeletal muscle, and
(b) the mechanisms that underlie alterations in glucose entry and its conversion to lipids for storage in white adipose tissue.

These studies will help to elucidate the mechanisms by which the efficient metabolism that drives fat storage after periods of poor growth confers to the phase of subsequent catch-up growth its increased sensitivity towards development of chronic metabolic diseases centered upon insulin resistance and hyperinsulinemia. 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 and cardiovascular insults, during critical periods of growth and development.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

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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
102156 Mechanisms by which suppressed thermogenesis in skeletal muscle predispose to insulin resistance and hypertension 01.10.2003 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
130481 Mechanisms of impaired glucose homeostasis during catch-up growth - a risk factor for later obesity and metabolic syndrome 01.07.2010 Project funding

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