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Trends in the prevalence of obesity/MetS
After remaining at a relatively stable level throughout the years 1960-‐1980, the past three decades has seen a more marked increase in the prevalence of obesity as measured by BMI. While the United States has experienced the most drastic shift, with the prevalence of obese adults more than tripling between the years 1980 and 2008 (Ogden and Carroll, 2010), a similar pattern can be observed in most western countries. In France for instance, the prevalence of adults with BMI > 30 increased from 8,5 to 15% just between 1997 and 2012 (Le Goff et al).
To account for this staggering increase in the prevalence of obesity and related comorbidities, many putative causes have been put forward. Most frequently mentioned are increased food intake due to greater and easier access to fast foods, as well as a decrease in physical activity due to motorized transports, growing prevalence of sedentary “desk jobs” and increasing leisure time spent with sedentary activities such as watching television and playing computer games.
Due to the proliferation of different diagnostic criteria, the prevalence and trends in MetS is more complicated to assess. In the US, the prevalence of the central component of MetS – abdominal obesity – more than tripled from 12,7 to 38,3% in men and from 19,4 to 59.9% in women (Okosun et al., 2004). The age-‐adjusted prevalence of MetS increased from 24,1 to 27% between the two measurement periods 1988-‐1994 and 1999-‐2000 (Ford et al., 2004), it is considered to currently affect between 25-‐30% of the population of US and Europe (Grundy, 2008).
Childhood obesity and adult disease
Childhood obesity has consistently been found to be a strong risk factor for obesity and its associated comorbidities in adulthood (Park et al. 2012; Allcock et al. 2009). Although it remains unclear whether the increased risk for such morbidities is merely due to the strong tendency for childhood obesity to persist in adulthood, there is evidence that the adverse effects of childhood obesity on health in adulthood, such as increased risk of coronary heart disease, diabetes, colorectal cancer, arthritis and gout, may be independent of whether the individual remains obese in adulthood (Must et al., 1992). Childhood obesity thus provides one important example of how an adverse metabolic state during the important periods of childhood development may impact the long-‐term metabolic health of the individual.
History and epidemiological evidence
The first clues that fetal malnutrition was linked to adult disease came from data on infant mortality in the UK in the early 20th century. The dominant cause of infant death at the time was low birth weight, and the regional pattern of infant mortality was later found to closely mirror the mortality from cardiovascular disease some 50 years later (Barker and Osmond, 1986). A link between low birth weight and increased risk of cardiovascular disease, hypertension and type 2 diabetes was later established in studies on cohorts of infants born around the same time (Hales et al., 1991; Fall et al., 1995).
The Dutch winter famine & the Stalingrad siege
The first evidence that directly linked fetal malnutrition to adult disease came from the cohort of infants born during the Dutch Winter Famine following the Second World War. In November 1944, the Germans enacted an embargo on food transport into the Netherlands that resulted in a brief but severe food shortage throughout the country, where the daily rations rapidly dropped below 1000 kcal/day and for a period between December 1944 and April 1945 was between 400 – 800 kcal/day, before th Netherlands were liberated in May 1945 and the food rations subsequently rose to more
than 2000 kcal/day. Infants undergoing gestation during this brief period of famine were found to be significantly heavier as adults, had a higher incidence of heart disease, and diabetes, and reported poorer general health than infants that were born before or conceived after the famine (Roseboom et al., 2001).
However, these effects were found to depend on the period of gestation during which famine exposure took place. Men exposed during the first half of gestation almost doubled their risk of obesity as adults, whereas men exposed later in gestation or just after birth had a lower risk of obesity (Ravelli et al., 1976). Similarly, many of the varied adverse health effects were only found in infants exposed during early gestation (Roseboom et al., 2006). The Dutch cohort thus provided an important clue as to the existence of critical periods of development, during which a growing foetus would be particularly sensitive to environmental insults. Since early gestation exposure to famine was not even found to affect the birth weight of the foetus, these studies further suggest that the programming effects of fetal malnutrition may be independent of overall fetal growth (Schulz, 2010), providing a new dimension to the concept of foetal programming that was not evident from previous studies on the association of birth weight wi2.2 History and epidemiological evidence
The first clues that fetal malnutrition was linked to adult disease came from data on infant mortality in the UK in the early 20th century. The dominant cause of infant death at the time was low birth weight, and the regional pattern of infant mortality was later found to closely mirror the mortality from cardiovascular disease some 50 years later (Barker and Osmond, 1986). A link between low birth weight and increased risk of cardiovascular disease, hypertension and type 2 diabetes was later established in studies on cohorts of infants born around the same time (Hales et al., 1991; Fall et al., 1995).
Table of contents :
Index
Acknowledgements
Scientific
communications
Abbreviations
Abstract
Resumé
Introduction
1. The epidemic of metabolic disease
1.1. Definition of obesity and the metabolic syndrome
1.1.1. Obesity
1.1.2. The Metabolic syndrome
1.2. Trends in the prevalence of obesity and MetS
1.3. Childhood obesity
1.3.1. Trends in prevalence.
1.3.2. Childhood obesity and adult disease
2. The developmental origins of metabolic disease
2.1. The Barker Hypothesis
2.2. History and epidemiological evidence
2.2.1. The Dutch winter famile and the Stalingrad siege
2.3. Animal models of developmental programming of disease
2.3.1. Intra-‐uterine growth restriction
2.3.2. Postnatal undernutrition
2.4. Perinatal overnutrition and adult disease
2.4.1. Epidemiology
2.4.2. Animal models of perinatal overnutrition
2.5. The Small Litter Model
2.5.1 Description
2.5.2. History
2.5.3. Pathophysiological and endocrine aspects
2.5.4. Species, strain and sex considerations
2.5.5. Methodological considerations
2.5.6. Mechanisms of programming by SL rearing
3. Hypothalamic regulation of energy balance
3.1. The Hypothalamus
3.1.1. History
3.1.2. The Arcuate Nucleus (ARH)
3.1.3. The Paraventricular Nucleus (PVH)
3.1.4. The Ventromedial Nucleus (VMH)
3.1.5. The Dorsomedial Nucleus (DMH)
3.1.6. The Lateral Hypothalamic Area (LHA)
3.2. Peripheral inputs onto hypothalamic feeding circuits
3.2.1. Access of peripheral signals to the hypothalamus
3.2.2. Glucose
3.2.3. Lipids
3.2.4. Ghrelin
3.2.5. Leptin
3.2.6. Insulin
3.2.7. Other hormones
4. Environmental control of developmental programming
4.1. Perinatal development of the hypothalamus
4.1.1. Embryonic development
4.1.2. Postnatal development
4.2. Endocrine regulation of hypothalamic development
4.2.1. Leptin
4.2.2. Ghrelin
4.2.3. Insulin
4.3. Role of perinatal nutrition in hypothalamic development……
4.3.1. Pre-‐ and postnatal undernutrition
4.3.2. Pre-‐ and postnatal overnutrition
Aims of the study
Results
Article
Discussion
Conclusions
Bibliography
