25 Life-course induction of adiposity

Imkongtenla Pongen and Meenal Dhall

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Contents:

 

1.        Induction and tracking of phenotype

1.1 Mechanisms involved in induction of body composition

2.        Induction of the size of the body

3.        Induction of body composition of neonatal

4.        Induction of body composition by fetal experience

5.        Post-natal growth induction of body composition

6.        Childhood induction of body composition

7.        Induction of rate of maturation 7.1 Effects of transgeneration

8.  Limitations in phenotypic induction

Summary

 

Learning Objectives:

 

1.   Elucidate the induction and tracking of phenotype.

2.   Delve into the mechanisms involved in body composition induction.

3.   Describe the induction of body size.

4.   Explain the induction of neonatal body composition

5.   Describe the induction of body composition by fetal experience.

6.   Find out how body composition is induced in childhood.

7.   Find out the induction of rate of maturation.

8.   Explore the effects of transgeneration and the linitations in phenotypic induction.

    Introduction

 

The content of body fat and its distribution varies across the life-course and between genders upto a great extent. Sexual dimorphism is seen from fetal stage and subsequently increases from puberty and gradually decreases with ageing. Besides this ontogenetic pattern of development which is unique to humans, individual growth trajectories and the influence of environment on adiposity should be taken into account.

 

Understanding life-course induction of adiposity would highlight the role of adipose tissue and lean mass in biological functions and the projection of adiposity of one generation in relation to the experience faced in the previous generation. Adiposity is expressed according to the size and physique. This module delineates the different aspect of body composition in the developmental trajectory of life span. Early life energy stores are essential component for this trajectory and it could also be linked to reproductive function especially among females.

 

1. Induction and tracking of phenotype

 

During 1960’s,nutritionists Mc Cance and Widowson demonstrated that those rats who were malnourished in early infancy had low body weight throughout life while those who suffered malnourishment later in life had temporary loss of weight which were easily recovered with proper intake of food. Davison and Dobbing, (1968) gave the concept of ‘period of sensitivity’ or ‘critical windows’ in the developmental process. This concept says that the long-term effects on the phenotype of organism are generated by environmental factors. The affected outcomes are body size, body composition, the rate of maturation, metabolism and risk of lifestyle diseases.

 

In 1991, ‘nutritional programming’ concept was brought by Lucas which says that nutrition in early life affects the health status later in life. Waterland and Garza, (1999) also brought in the concept of ‘metabolic imprinting’ which means that the environmental stimuli have a tendency to affect permanently the structure and function of the organism. However, Bateson (2001) criticized ‘programming’ since it gives an incorrect suggestion that early environmental stimuli consist of instructions for diseases later in life. He has argued that the concept of phenotypic induction is more relevant as it fits closely with developmental biology. In recent times, programming is used by those researchers involved in early life etiology of certain diseases. Those involved in evolutionary and developmental biology use the concept of phenotypic induction.

 

According to Wells (2009), metabolic capacity refers such physiological traits that shows close association with organogenesis and are sensitive to experience during the fetal stage. Metabolic load refers to the growth in size and mass of tissue. When metabolic load exceeds metabolic capacity, risk of disease becomes greatest.

 

Phenotypic induction consists of two components, viz, the difference in phenotype which emerges during initial critical window periods and tracking the phenotype once the critical period gets over.

 

A trait becomes resistant to environmental conditions when it is canalized and possess the ‘self righting’ ability that generate only transient effects under environmental stress and the trajectory is retained once the stress is removed. Such plasticity in gaining weight and height as well as canalization of growth after the infant stage is seen in humans. As such, many metabolic capacity track into adulthood and due to this metabolic load increases which needs to be normalized for maintaining homeostasis. Those individuals with least metabolic capacity have little capacity to achieve this normalization, hence leading to appearance of symptoms of chronic diseases like glucose intolerance and hypertension.

 

Induction of body composition is firstly done through early nutrition or growth patterns. This kind of induction is brought through epigenetic changes or through the effects of hormones regulating childhood growth. Secondly, an important component of variability in growth rate from fetal life onwards is body composition (adiposity and lean mass).Lean mass includes the sum of mass of all organs such as the heart, liver, kidney and pancreas besides muscles which is vital to metabolic capacity and can also contribute to metabolic load (when there is increase in muscle mass during childhood and adolescence).

 

1.1 Mechanisms involved in induction of body composition

 

The mechanisms of body composition induction are- induction of appetite, rate of maturation, hormonal axes and epigenetic modifications. Epigenetic mechanisms can be seen in the case of fathers exposed to famine producing offspring with increased risk of obesity, but this mechanism usually operates in the mother. Phenotype of mother does not only induce body composition but even the rate of maturation.

 

2. Induction of the size of the body

 

Induction of body size is reflected by height and body mass index. Height can vary according to the rate at which height is attained and one does not lose height before attaining adulthood. Twin studies have thrown light on the association between early patterns of growth and later height because such studies remove the confounding by genetic factors. Differences in birth weight in monozygotic twins were found to be significantly correlated with differences in adult height demonstrating that intrauterine experience has greater effect on adult height but a weaker effect on adult weight.

 

Other studies have revealed that birth weight predicts height later in life. Studies have also identified different periods of time during which early life experience effects growth rate. A British cohort of 2547 girls born in 1946 were found to be associated with height in two years but was not associated with change in height between two and seven years. Girls who were heavier at birth reached menarche earlier than their counterparts.

 

Associations between birth weight and BMI have been demonstrated in many studies. It has been found that each kilogram increase in weight at birth was associated with 0.5 to 0.7 kg/m2 of BMI. This implies that those who were heavier at birth were also fatter and they happen to preserve their fatness even into later life. A J-shaped or U-shaped association between birth weight and BMI reflects a high prevalence of adiposity in low or high birth weight. However, much of these studies only shows that faster growth in fetal life leads to bigger size without distinguishing how general and regional adiposity is affected.

 

3. Induction of body composition of neonatal

 

Evidence of neonatal induction can be seen from the studies done on the effect of gestational age at birth. At birth, neonates have low levels of body fat because maximum fat deposition occurs at last trimester of pregnancy only. Infants who are born preterm and fed ex utero in the last trimester struggle to gain energy to achieve deposition of fats in utero. When full term age is reached, preterm babies continue to show low levels of fat and this continues into mid-childhood. Experience during fetal life affects body composition in neonates. This is supported by analyses of phenotype at birth. The influence of intrauterine retardation of growth on birth phenotype was strongest in the final trimester of pregnancy.

 

Neonates that were small for gestational age had reduced ponderal index i.e., weight adjusted for height, lower percentage of fat and decreased concentrations of leptin. Supplementation studies on malnourished women have revealed modest improvement in birth weight and the improvement could be seen only among women who were most malnourished at baseline. Weight gain during pregnancy is positively correlated with birth weight only in the offspring of mothers who had low weight at baseline. This indicates relatively modest influence of gross energy intake of mothers on the birth size of their offsprings.

 

Mothers who consume a higher glycemic-index diet produced offspring who were heavier and had higher ponderal index than their counterparts. Also women with gestational or type 1 diabetes produce fatter offspring. Thus phenotype of a mother is essential in the induction of fetal body composition, more important than diet during pregnancy. When there is adequate supply of maternal energy to the fetus, body composition at birth shows a high level of lean mass and peripheral distribution of fat mass. When the maternal energy is restricted then masses of both lean and fat mass decreases in the offspring with preservation of central fat at the peripheral’s fat expense.

 

4. Induction of body composition by fetal experience

 

There have been a number of studies exploring the association between birth weight and body composition. Birth weight act as an imperfect proxy for the environmental experience faced in the fetal stage because those with average or higher birth weight may have weakened in the earlier trimesters and those with low birth weight would have grown poorly during the last trimester. Those who experienced maternal famine during first trimester had increased risk of adult obesity while those who experienced maternal famine during last trimester had reduced risk of adult obesity. Female offspring who were undernourished have a more deposition of fat at the centre.

 

The third trimester is a critical period for deposition of fat. Higher values of adult BMI may represent lean mass rather than adiposity. In the first trimester of pregnancy, growth retardation is associated with increase in size during birth. These findings reveal maternal or offspring genotype rather than the life-course induction of adiposity. During famine condition, fatter mothers would have conceived more easily and thrifty offspring would have higher rates of survival.

 

Larger size at birth induces lean mass in greater amounts and in proportion to stature. Thus induction of lean mass of adults by fetal growth leads to achievement of normal duration of pregnancy. Long term programming of hormones might be a possible factor for the association between early and later body composition. Fat stores in neonates may be vital for providing energy for lean mass deposition in infants. Many studies have reported negative associations between size at birth and adult adiposity which is dependent on adjustment of current size using statistical methods. This could be explained by the account of variability attributable to post-natal rather than prenatal growth patterns.

 

Association of birth weight with later adiposity directs to the issue of association between variability in size at birth and variability in adiposity at birth. This is referred to as a ‘thin-fat’ phenotype which comprises of reduced lean mass but high fat mass. However it remains unresolved whether such a thin-fat baby reflects a thrifty genotype effect. Hence fetal experiences induce later body composition, the effect been more pronounced for lean mass indices than for adiposity indices. Weight gain during the post-natal stage which is associated to fetal growth is vital for the induction of adipose phenotype. Therefore birth weight may predict body composition without neonatal body composition been the cause of the pathway.

 

5. Post-natal growth induction of body composition

 

Weight gain during post-natal stage makes a pivotal contribution to onset of adult diseases. Risk of metabolic syndrome is highest among those who were born small and gained most weight during post natal period. This reveals the importance of the differences in rate of growth between different stages of life-course and emphasizes the relative contribution of different stages of post natal gain in weight to adult phenotype and disease risk. Rapid infant growth is associated with greater abdominal obesity. The effect of gain in weight on adult body composition differ between industrialized and developing countries. In European countries, greater gain of infant weight is associated with later weight, height, waist circumference, fat mass and lean mass increase in children and adolescence. Whereas among non-Western populations, weight gain of infants is associated only with later height, weight and lean mass increase but not fat mass.

 

A vital factor mediating growth of infants is the duration of the catch-up growth which is associated with later fat mass and the risk of been overweight. This happens only when the catch-up growth persists beyond the first year of life. Low birth weight babies happens to be sensitive to insulin at birth that helps in the promotion of catch up growth during infancy. When this catch up growth prolongs beyond infancy into early childhood insulin resistance develops which leads to accumulation of fat in the abdomen region. Excess accumulation of fat occurs after one year of age. Gain of weight in the first eight days of life was significantly associated with risk of been obese in adulthood.

 

Weight gain in preterm babies in the first two weeks of post natal stage was significantly associated with insulin resistance during adolescent stage. Those who were on low nutrient diet were found to have reduced insulin resistance during adolescence which could be due to slower rate of growth. This may likely represent the change of nutrition from placental to oral nutrition and the intake of low energy food by breast-fed infants.

 

Stunting is associated with increased risk of obesity since it may predispose the individual to increased intake of energy or reduced metabolic rate. The mode of feeding of infants has been associated with differences in growth rate or in body composition during infancy. Breast feeding is associated with decreased risk of obesity later in life as suggested by body mass index but studies that have focused on body composition have failed to support this hypothesis. It is unclear whether biological components of breast milk might decrease growth rate or whether the easier way of formula feeding that maximize intake could promote growth rate. There is need for further studies to address the differences between Western and non-Western countries with respect to early life induction of adiposity to further implement the policies for care of infants.

 

6. Childhood induction of body composition

 

Gain in weight during childhood also influence later body composition. Adiposity rebound, i.e., the age at which childhood BMI reaches a natural point before increasing again, was a significant predictor of adiposity. But in recent times it is considered as a misnomer because rebound is a function of the magnitude of initial BMI. It is not certain whether weight gain during childhood is an induction of phenotype since linear growth is been canalized and any effect on fatness is reversible theoretically. With the procession of childhood, tracking of BMI becomes stronger. Tracking in ratios of skinfold is attributable to the genetic factors that affect the phenotype through life-course. There is also short term tracking of adiposity between the end of infancy and mid-childhood. Such tracking apply more to physique than adiposity. Height, physique and lean mass can be tracked mostly from early life within any population. Under ecological fluctuations, within population ranking in lean mass is likely to be more stable than within population ranking in fat mass.

 

7. Induction of rate of maturation

 

The broader trend of precocious puberty could be traced to secular trends in growth and diet although it may also be due to some specific pathological factors. Environmental factors exert stronger influence than genetic factors on initiation of menarche. Nutritional factors also have contrasting influence according to the time of the life course when they act. Rapid childhood weight gain has been associated with earlier puberty , the underlying mechanism been the hormone leptin instigating the onset of puberty. The pivotal effect of early puberty is to advance the attainment of increased body fat in the body. This variability in the timing of puberty effects the body size and composition. The age at menarche and body composition is heritable among females. Those with earlier menarche attained a shorter final height as compared to those who matured later.

 

Fatter and shorter mothers reproduce their phenotype in their daughters through earlier puberty, reduced growing period and faster infant growth. The fact that fast growth occurred during infancy strongly reflects a regulatory mechanism that is non-genetic. Earlier menarche mothers signal their energy stores to their offspring in utero that lead to faster post-natal growth. Shorter height of early menarche mothers has been associated with lower birth weight in female offspring owing to decrease in the size of the uterus. Faster post-natal rate of growth would therefore be a strategy to recover this deficit in the fetal growth.

 

The association of body composition of offspring and phenotype of mothers highlight the induction of body by trans-generational effects. Earlier menarche is strongly associated with risk of obesity and BMI independent of the influence of BMI during childhood period.

 

7.1 Effects of trans-generation

 

Early life induction of body composition establishes parental effect where there is tracking of body size and physique, subject to changes and exerts their biggest impact during fetal life and infancy. In each generation, induction of adiposity links the life course energy storage with tailoring of rate of growth and maturation to the interaction of availability of energy and maternal phenotype.

 

8. Limitations in phenotypic induction

 

Simple techniques have been adopted for measuring human body composition due to practical difficulties of taking measurements in large number of individuals at different ages. Moreover body composition does not involve only masses of tissues (eg, fat mass, lean mass, etc) but also components of size and shape of the body. A taller individual would have greater tissue mass therefore variability in body size ought to be taken into account. Since fat depots are distributed outside the muscular and skeletal structures, body shape shows close association with body composition. Investigations based on phenotypic induction have been limited to such methods.

 

Body mass index is used as an index of fatness of a body and waist-hip ratio (WHR) and skinfold thicknesses have been used to assess abdominal adiposity. However, body shape and fat distribution cannot be assessed by BMI. Differences in WHR between individuals may highlight physique (hip girth) as much as central adiposity. A high ratio of triceps to subscapular skinfold may reveal a low value of triceps or high value of subscapular which reflects an independent index of abdominal fat that is not reliable.

 

Summary

 

The life course induction and tracking of body composition consists of both lean mass and adiposity. Quality measurements are essential to interpret these phenomena. Good maternal phenotype as revealed in large size and good amount of energy reserves, are found to be associated with a larger neonate with greater lean mass that tracks into adulthood. Poor maternal phenotype leads to constrains in offspring size and lean mass that gets tracked through malnutrition of the offspring during post-natal stage. Under such circumstances, the ratio of lean mass to fat changes with potential influence on distribution of fat and insulin metabolism especially with occurrence of catch-up growth. There is less evidence of tracking of adiposity from childhood onwards because the underlying predisposition for a level of fatness may be responsive to environmental and behavioral changes. The phenotype of adiposity is mostly sensitive to the interaction between rate of growth during fetal and early post-natal periods. This implies that exposure to maternal phenotype is the main determinant of induction of phenotype.

 

Maternal phenotype induces the phenotype of offspring which is suggested by the U-shaped association between birth weight and adult obesity status. One of the reason for this could be that the low birth weight infants induces an extra metabolic load through their catch-up growth while high weight infants would have already begun this in utero. This kind of hypothesis comes from studies linking higher weight at birth with decreased growth in the first trimester and the higher level of obesity among high birth weight babies.

 

There is variation in transgenerational transfer of maternal ‘capital’ from the perspective of evolution. High or best quality motherhood invest in bigger offspring and use its adipose reserves to increase the rate of infant growth so that the offspring could breed earlier than usual. This is a fitness enhancing strategy since the larger body size improves the lactation energy. Similarly poor quality motherhood produces small offspring who may require to extend their total period of growth to reach their reproductive period. Smaller offsprings may also change their ‘investment strategies’ during the process of growth to gain higher adipose tissues. Across generations, the ontogenetic development of body composition is an adaptive strategy.

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GLOSSARY

  Induction- The process or mechanism brought about by an action that gives rise to various forms of something.

 

Adiposity- The state of being fat.

 

Adiposity rebound – Age during which childhood BMI reaches a natural point before increasing again.

 

Precocious puberty– The attainment of puberty very early in age.

 

Phenotype– It is a set of observable characters which is caused by the result of different interaction of genotypes.

 

Neonatal– A newborn child to the first month of birth.

 

Waist-hip ratio (WHR) – The circumference ratio of waist to that of hip.

 

Lean mass – The sum of mass of all organs such as the heart, liver, kidney and pancreas which is vital to metabolic capacity and can also contribute to metabolic load.

 

Did you know?

 

Infants who are born preterm and fed ex-utero in the last trimester struggle to gain energy to achieve deposition of fats in utero.

 

Interesting facts

  1. Larger size at birth induces lean mass in greater amounts and in proportion to stature. Thus induction of lean mass of adults by fetal growth leads to achievement of normal duration of pregnancy.
  2. Phenotype of a mother is essential in the induction of fetal body composition, more important than diet during pregnancy

    Points to ponder:

 

Environmental factors exert stronger influence than genetic factors on initiation of menarche. Nutritional factors also have contrasting influence according to the time of the life course when they act.

 

References

  1. Wells, J. C. (2007). Environmental Quality, Developmental Plasticity and the Thrifty Phenotype: A Review of Evolutionary Models. Evolutionary Bioinformatics Online, 3, 109– 120.
  2. Wells, J. C. (2007). The Thrifty Phenotype as an adaptive maternal effect. Biol. Rev , 82, 143– 172.
  3. Wells, J.C. (2009). The life-course induction of adiposity. In the Evolutionary Biology of Human Body Fatness:Thrift and Control. Cambridge University Press
  4. http://www.sfu.ca/biology/courses/bisc441/Course_Materials/Readings/28-(Lect15)Wells.pdf

    Suggested Readings

  1. Haig D. Genetic conflicts in human pregnancy. Q. Rev. Biol,68:495–532
  2. Ibáñez L, Ong K, et al.(2006). Early development of adiposity and insulin resistance after catch-up weight gain in small-for-gestational-age children. J. Clin. Endocrinol. Metab,91:2153–8
  3. Kuzawa CW. (2001).Fetal origins of developmental plasticity: are foetal cues reliable predictors of future nutritional environments. Am. J. Hum. Biol, 17:5–21
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  7. Stettler N, Stallings VA, Troxel AB, Zhao J, Schinnar R, Nelson SE, Ziegler EE, Strom BL. (2005).Weight gain in the first week of life and overweight in adulthood: a cohort study of European American subjects fed infant formula. Circulation, 111:1897–903
  8. https://www.researchgate.net/publication/237135551_Adult_Disease_Induction_and_Life_Cou rse_Events_Some_Perspectives_from_a_Resource-compromised_Economy
  9. http://www.nature.com/ijo/journal/v33/n12/full/ijo2009175a.html