Thrifty phenotype

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The thrifty phenotype hypothesis says that reduced fetal growth is strongly associated with a number of chronic conditions later in life, including coronary heart disease, stroke, diabetes, and hypertension. This increased susceptibility is said to result from adaptations made by the fetus in an environment limited in its supply of nutrients. The thrifty phenotype is a component of the fetal origins hypothesis.

Contents

Evolutionary rationale

Benefit for offspring

Proponents of this idea say that in poor nutritional conditions, a pregnant woman can modify the development of her unborn child such that it will be prepared for survival in an environment in which resources are likely to be short, resulting in a thrifty phenotype (Hales & Barker, 1992 [1] [2] ). It is sometimes called Barker's hypothesis, after Professor David J. P. Barker, researching at the University of Southampton who published the theory in 1990. [3]

The thrifty phenotype hypothesis suggests that early-life metabolic adaptations help in survival of the organism by selecting an appropriate trajectory of growth in response to environmental cues. Recently, some scientists have proposed that the thrifty phenotype prepares the organism for its likely adult environment in long term.

Benefit for mother

However, environmental changes during early development may result in the selected trajectory becoming inappropriate, resulting in adverse effects on health. This paradox generates doubts about whether the thrifty phenotype is adaptive for human offspring. Thus, the thrifty phenotype should be considered as the capacity of all offspring to respond to environmental cues during early ontogenetic development. It has been suggested that the thrifty phenotype is the consequence of three unlike adaptive processes: maternal effects, niche construction and developmental plasticity, which all are influenced by the brain. While developmental plasticity demonstrates an adaptation by the offspring, niche construction and parental effects are result of parental selections rather than offspring fitness. Therefore, the thrifty phenotype can be described as a manipulation of offspring phenotype for the benefit of maternal fitness. The information that enters offspring phenotype during early development mirror the mother's own developmental experience and the quality of the environment during her own maturation rather than predicting the possible future environment of the offspring [4]

Adverse effects

Many human diseases in adulthood are related to growth patterns during early life, determining early-life nutrition as the underlying mechanism. Individuals with a thrifty phenotype will have "a smaller body size, a lowered metabolic rate and a reduced level of behavioural activity… adaptations to an environment that is chronically short of food" (Bateson & Martin, 1999 [5] ). Those with a thrifty phenotype who actually develop in an affluent environment may be more prone to metabolic disorders, such as obesity and type II diabetes, whereas those who have received a positive maternal forecast will be adapted to good conditions and therefore better able to cope with rich diets. This idea (Barker, 1992 [6] ) is now widely (if not universally) accepted and is a source of concern for societies undergoing a transition from sparse to better nutrition (Robinson, 2001 [7] ).

Risk factors of thrifty phenotype include advanced maternal age and placental insufficiency. [8]

Molecular mechanisms

The ability to conserve, acquire and expend energy is believed to be an innate, ancient trait that is imbedded in the genome in a way that is quite protected against mutations. [9] These changes are also believed to possibly be inherited across generations. [9] Leptin has been identified as a possible gene for the acquisition of these thrifty traits. [9]

On a larger anatomic scale, the molecular mechanisms are broadly caused by a suboptimal environment in the reproductive tract or maternal physiological adaptations to pregnancy. [8]

See also

Related Research Articles

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Intrauterine growth restriction Medical condition

Intrauterine growth restriction (IUGR), or fetal growth restriction, refers to poor growth of a fetus while in the womb during pregnancy. IUGR is defined by clinical features of malnutrition and evidence of reduced growth regardless of an infant's birth weight percentile. The causes of IUGR are broad and may involve maternal, fetal, or placental complications.

A maternal effect is a situation where the phenotype of an organism is determined not only by the environment it experiences and its genotype, but also by the environment and genotype of its mother. In genetics, maternal effects occur when an organism shows the phenotype expected from the genotype of the mother, irrespective of its own genotype, often due to the mother supplying messenger RNA or proteins to the egg. Maternal effects can also be caused by the maternal environment independent of genotype, sometimes controlling the size, sex, or behaviour of the offspring. These adaptive maternal effects lead to phenotypes of offspring that increase their fitness. Further, it introduces the concept of phenotypic plasticity, an important evolutionary concept. It has been proposed that maternal effects are important for the evolution of adaptive responses to environmental heterogeneity.

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Protein–energy malnutrition Medical condition

Protein–energy malnutrition (PEM), sometimes called protein-energy undernutrition (PEU), is a form of malnutrition that is defined as a range of conditions arising from coincident lack of dietary protein and/or energy (calories) in varying proportions. The condition has mild, moderate, and severe degrees.

The thrifty gene hypothesis, or Gianfranco's hypothesis is an attempt by geneticist James V. Neel to explain why certain populations and subpopulations in the modern day are prone to diabetes mellitus type 2. He proposed the hypothesis in 1962 to resolve a fundamental problem: diabetes is clearly a very harmful medical condition, yet it is quite common, and it was already evident to Neel that it likely had a strong genetic basis. The problem is to understand how disease with a likely genetic component and with such negative effects may have been favoured by the process of natural selection. Neel suggested the resolution to this problem is that genes which predispose to diabetes were historically advantageous, but they became detrimental in the modern world. In his words they were "rendered detrimental by 'progress'". Neel's primary interest was in diabetes, but the idea was soon expanded to encompass obesity as well. Thrifty genes are genes which enable individuals to efficiently collect and process food to deposit fat during periods of food abundance in order to provide for periods of food shortage.

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Maternal obesity refers to obesity of a woman during pregnancy. Parental obesity refers to obesity of either parent during pregnancy.

The "drifty gene hypothesis" was proposed by the British biologist John Speakman as an alternative to the thrifty gene hypothesis originally proposed by James V Neel in 1962.

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Nutriepigenomics is the study of food nutrients and their effects on human health through epigenetic modifications. There is now considerable evidence that nutritional imbalances during gestation and lactation are linked to non-communicable diseases, such as obesity, cardiovascular disease, diabetes, hypertension, and cancer. If metabolic disturbances occur during critical time windows of development, the resulting epigenetic alterations can lead to permanent changes in tissue and organ structure or function and predispose individuals to disease.

Transgenerational epigenetic inheritance

Transgenerational epigenetic inheritance is the transmission of epigenetic markers from one organism to the next that affects the traits of offspring without altering the primary structure of DNA —in other words, epigenetically. The less precise term "epigenetic inheritance" may cover both cell–cell and organism–organism information transfer. Although these two levels of epigenetic inheritance are equivalent in unicellular organisms, they may have distinct mechanisms and evolutionary distinctions in multicellular organisms.

A predictive adaptive response (PAR) is a developmental trajectory taken by an organism during a period of developmental plasticity in response to perceived environmental cues. This PAR does not confer an immediate advantage to the developing organism; however, if the PAR correctly anticipates the postnatal environment it will be advantageous in later life, if the environment the organism is born into differs from that anticipated by the PAR it will result in a mismatch. PAR mechanisms were first recognized in research done on human fetuses that investigated whether poor nutrition results in the inevitable diagnosis of Type 2 diabetes in later life. PARs are thought to occur through epigenetic mechanisms that alter gene expression, such as DNA methylation and histone modification, and do not involve changes to the DNA sequence of the developing organism. Examples of PARs include greater helmet development in Daphnia cucullata in response to maternal exposure to predator pheromones, rats exposed to glucocorticoid during late gestation led to an intolerance to glucose as adults, and coat thickness determination in vole pups by the photoperiod length experienced by the mother. Two hypotheses to explain PAR are the "thrifty phenotype" hypothesis and the developmental plasticity hypothesis.

The fetal origins hypothesis proposes that the period of gestation has significant impacts on the developmental health and wellbeing outcomes for an individual ranging from infancy to adulthood. The effects of fetal origin are marked by three characteristics: latency, wherein effects may not be apparent until much later in life; persistency, whereby conditions resulting from a fetal effect continue to exist for a given individual; and genetic programming, which describes the 'switching on' of a specific gene due to prenatal environment. Research in the areas of economics, epidemiology, and epigenetics offer support for the hypothesis.

Intragenomic and intrauterine conflicts in humans arise between mothers and their offspring. Parental investment theory states that parents and their offspring will often be in conflict over the optimal amount of investment that the parent should provide. This is because the best interests of the parent do not always match the best interests of the offspring. Maternal-infant conflict is of interest due to the intensity of maternal investment in her offspring. In humans, mothers often invest years of care into their children due to the long developmental period before children become self-sufficient. 

Fetal programming, also known as prenatal programming, is the theory that environmental cues experienced during fetal development play a seminal role in determining health trajectories across the lifespan.

The Summermatter cycle is a physiological concept describing the complex relationship between physical activity/inactivity and energy expenditure/conservation.

Dr. Kent L. Thornburg, Ph.D. is an American scientist, researcher and professor. He lives in Portland, Oregon and works at Oregon Health & Science University (OHSU), in the School of Medicine. He is the director for both the OHSU Center for Developmental Health and the Moore Institute for Nutrition & Wellness

Simon Langley-Evans is Professor of Human Nutrition at the University of Nottingham. He obtained his BSc in Biochemistry and Microbiology from Royal Holloway and Bedford New College, University of London in 1986. His PhD was from the University of Southampton (1990). Langley-Evans was the winner of the Nutrition Society Silver Medal in 2005. In 2012 he was awarded a DSc from the University of Nottingham in recognition of his contribution to research into the early life origins of adult disease. His principal contribution was the development of experimental models to test the hypothesis that variation in maternal nutrition during pregnancy could programme long-term health and disease.

References

  1. Hales CN, Barker DJ (July 1992). "Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis". Diabetologia. 35 (7): 595–601. doi: 10.1007/BF00400248 . PMID   1644236.
  2. Hales, CN; Barker, DJ (2001). "The thrifty phenotype hypothesis". British Medical Bulletin. 60: 5–20. doi: 10.1093/bmb/60.1.5 . PMID   11809615.
  3. Barker, D.J.P. (1997). "Maternal Nutrition, Fetal Nutrition, and Disease in Later Life". Nutrition, '13', pg. 807
  4. Wells JC (February 2007). "The thrifty phenotype as an adaptive maternal effect". Biol Rev Camb Philos Soc. 82 (1): 143–72. doi:10.1111/j.1469-185X.2006.00007.x. PMID   17313527.
  5. Martin, Paul; Bateson, Patrick (1999). Design for a life: How behaviour develops. London: Jonathan Cape. pp. 110–1. ISBN   0-224-05064-8.
  6. Barker, D. J. P., ed. (1992). Fetal and infant origins of adult disease. London: British Medical Journal. ISBN   0-7279-0743-3.
  7. Robinson R (February 2001). "The fetal origins of adult disease : No longer just a hypothesis and may be critically important in south Asia". BMJ. 322 (7283): 375–6. doi:10.1136/bmj.322.7283.375. PMC   1119617 . PMID   11179140. Editorial
  8. 1 2 Aiken, C. E.; Ozanne, S. E. (2013). "Transgenerational developmental programming". Human Reproduction Update. 20 (1): 63–75. doi: 10.1093/humupd/dmt043 . PMID   24082037.
  9. 1 2 3 Stöger R (February 2008). "The thrifty epigenotype: an acquired and heritable predisposition for obesity and diabetes?". BioEssays. 30 (2): 156–66. doi:10.1002/bies.20700. PMID   18197594.