Posts Tagged ‘phenotype’

Genetic Basis of Obesity

September 26th, 2009

Often one hears it stated that obesity is not a genetic disease. If by that the speaker is saying that obesity is probably not due to a single genetic change they are not quite right. There are some rare forms of obesity which are due to a single gene change. Genetic obesity syndromes. [Front Horm Res. 2008] – PubMed Result; Genetic and hereditary aspects of childhood obesit…[Best Pract Res Clin Endocrinol Metab. 2005] – PubMed Result But if they mean a single genetic change cannot account for a worldwide epidemic of obesity occurring over the last 30 years they are probably right. If the speaker means it is unlikely that there will be a treatment for obesity based on gene therapy, they are probably correct. (Although who can predict the future?) However, they miss the point if they do not understand that for millions of years of evolution, the species we call humans have favored genes which maximize its chances for survival and reproduction. So our taste preferences, our physical activity preferences and the like are passed on in the genome and our part of our inheritance. The problem is that for centuries we humans lived in an environment which was totally different than the one we live in now. The disconnect is that our bodies have not yet adapted to this new world where tasty, nutritious food is readily available and where most of us do not have to expend anything other than a minimal effort to obtain it, survive and flourish. Anything policy-makers or parents want to do about obesity must be understood in the context of the powerful force evolution has been in designing how humans acquire, store and use energy from food.

According the CDC:

  1. Biological relatives tend to resemble each other in many ways, including body weight. Individuals with a family history of obesity may be predisposed to gain weight.
  2. Different responses to the food environment are largely due to genetic variation between individuals.
  3. Fat stores are regulated over long periods of time by complex systems that involve input and feedback from fat tissue, the brain and endocrine glands like the pancreas and the thyroid. http://www.cdc.gov/genomics/training/perspectives/files/obesknow.htm,
  4. The tendencies to overeat and be sedentary, the diminished ability to use dietary fat as fuel and enlarged, easily stimulated capacity to store body fat are all genetically influenced. The variation in how individuals respond to the food rich environment and the differences in acquiring obesity related comorbid conditions are also genetically determined. http://www.cdc.gov/Features/Obesity/

Since 1997, published studies have found that variation in BMI is largely due to heritable genetic differences, with estimates ranging from 55% to 85%. A 2008 study found that 77% of the adiposity in preadolescent children born since the start of the obesity epidemic was due to genetic inheritance compared to 10% for the environment. Evidence for a strong genetic influence on childho…[Am J Clin Nutr. 2008] – PubMed Result

A fast rate of eating appears to be heritable. Eating rate is a heritable phenotype related to we…[Am J Clin Nutr. 2008] – PubMed Result Differences in responding to the obesogenic environment may also be heritable Genetic influence on appetite in children. [Int J Obes (Lond). 2008] – PubMed Result and Appetite is a Heritable Phenotype Associated with …[Ann Behav Med. 2009] – PubMed Result. The FTO gene may be involved. The FTO gene and measured food intake in children. [Int J Obes (Lond). 2009] – PubMed Result and Increasing heritability of BMI and stronger associ…[Obesity (Silver Spring). 2008] – PubMed Result Parental leanness appears to provide strong protection against the development of obesity in children. Development of overweight in children in relation …[Obesity (Silver Spring). 2009] – PubMed Result

There is an interesting scientific debate about what is called the “thrifty gene” hypothesis about how a genetic preference for storing extra energy on our bodies might have developed. Thrifty genes for obesity, an attractive but flawe…[Int J Obes (Lond). 2008] – PubMed Result and The clinical biochemistry of obesity. [Clin Biochem Rev. 2004] – PubMed Result. Some think that childhood obesity is increasing due to ‘associative mating’ by overweight parents who pass on their genetic disposition to obesity to their children. Childhood obesity: are genetic differences involve…[Am J Clin Nutr. 2009] – PubMed Result

The evidence for the genetic basis of obesity, in addition to environmental changes is quite strong. See Implications of gene-behavior interactions: preven…[Obesity (Silver Spring). 2008] – PubMed Result; Genome-wide association scan shows genetic variant…[PLoS Genet. 2007] – PubMed Result and The genetics of obesity. [Metabolism. 1995] – PubMed Result

The environment is thought to be responsible for variations between populations but genetics is responsible for the variations within a given population. Obesity – Missing Heritability and GWAS Utility and Genetic and environmental factors in relative body…[Behav Genet. 1997] – PubMed Result. Genetics may account for many cases of morbid obesityFamilial aggregation of morbid obesity. [Obes Res. 1993] – PubMed Result.

Genetics may play an important role in determining who can benefit from different types of intervention. Implications of gene-behavior interactions: preven…[Obesity (Silver Spring). 2008] – PubMed Result or who is more likely to be affected by obesity Ethnic variability in adiposity and cardiovascular…[Int J Epidemiol. 2009] – PubMed Result. Or experience a comorbid condition like Type 2 diabetes Mechanisms of disease: genetic insights into the e…[Nat Clin Pract Endocrinol Metab. 2008] – PubMed Result

The FTO gene is currently under active research interest for providing a link to how obesity related conditions might arise and how patients can benefit from this knowledge. FTO: the first gene contributing to common forms o…[Obes Rev. 2008] – PubMed Result Genome-wide association scan shows genetic variant…[PLoS Genet. 2007] – PubMed Result

The FTO gene may explain different responses to exercise. FTO Genotype Is Associated With Exercise Training-…[Obesity (Silver Spring). 2009] – PubMed Result .Physical activity and the association of common FT…[Arch Intern Med. 2008] – PubMed Result

A factor in the resistance to describe obesity as a genetic disease may be in the assumption that the human genome does not change rapidly whereas the increase globally in the rates of obesity have occurred in the last 40-50 years. However, evolutionary biologists are debating the speed of genetic change. In “Catching Fire, How Cooking Made us Human” (Basic Books, New York, 2009) Richard Wrangham, the Ruth Moore Professor of Biological Anthropology at Harvard University writes,

A long delay between the adoption of a major new diet and resulting changes in anatomy is also unlikely. Studies of Galapagos finches by Peter and Rosemary Grant showed that during a year when finches experiences an intense food shortage caused by an extended drought, the birds that were best able to eat large and hard seeds – those birds with the largest beaks- survived best. The selection pressure against small-beaked birds was so intense that only 15 percent of birds survived and the species as a whole developed measurably larger beaks within a year. Correlations in beak size between parents and offspring showed that the changes were inherited. Beak size fell again after the food supply returned to normal, but it took about fifteen years for the genetic changes the drought had imposed to reverse. The Grants’ finches show that anatomy can evolve very quickly in response to dietary changes…Other data show that if an ecological change is permanent, the species also changes permanently, and again the transition is fast…The adaptive changes brought on by the adoption of cooking would surely have been rapid. (p. 93-94, emphasis added.) (See Book Reviews)

Inheritance Factors

September 26th, 2009

Genes are not the only way characteristics may be passed from generation to generation. Researchers are actively pursuing what is called epigenetics. Epigenetics refers to changes in appearance, or phenotype, which is not due to changes in the DNA, which regulates genes and their expression.

Intrauterine Environment

The intrauterine environment (the womb) has been shown to affect the child’s disposition to obesity. Fetal origins of obesity. [Obes Res. 2003] – PubMed Result and Programming of body composition by early growth an…[Proc Nutr Soc. 2007] – PubMed Result Maternal and child obesity: the causal link. [Obstet Gynecol Clin North Am. 2009] – PubMed Result Gestational weight gain may predispose offspring to obesity and high blood pressure Associations of gestational weight gain with offsp…[Circulation. 2009] – PubMed Result and Gestational weight gain and risk of overweight in …[Am J Clin Nutr. 2008] – PubMed Result

Multiple factors are probably at work leading to an increased risk of developing obesity. Developmental origins of childhood overweight: pot…[Obesity (Silver Spring). 2008] – PubMed Result and Early determinants of overweight at 4.5 years in a…[Int J Obes (Lond). 2006] – PubMed Result

The question is to what extent the genes or the intrauterine environment influence the progression to adult obesity. The influence of birthweight and intrauterine envi…[Int J Obes Relat Metab Disord. 2003] – PubMed Result

One way in which the fetus might be affected in his or her development is by enhanced nutrition in the womb

Intrauterine changes are thought by some to contribute to the increase in obesity in India. Obesity epidemic in India: intrauterine origins? [Proc Nutr Soc. 2004] – PubMed Result

Maternal weight gain during pregnancy may affect the baby’s birth weight and long term risks Gestational weight gain and child adiposity at age…[Am J Obstet Gynecol. 2007] – PubMed Result

Detrimental influences in the womb, such as smoking Maternal smoking during pregnancy and child overwe…[Int J Obes (Lond). 2008] – PubMed Result, Association of maternal lifestyles including smoki…[Obesity (Silver Spring). 2007] – PubMed Result, Associations of maternal prenatal smoking with chi…[Obes Res. 2005] – PubMed Result, and famine The Dutch Famine of 1944-1945: a pathophysiologica…[Curr Opin Clin Nutr Metab Care. 2006] – PubMed Result or harmful chemicals Developmental exposure to endocrine disruptors and…[Reprod Toxicol. 2007 Apr-May] – PubMed Result and Role of nutrition and environmental endocrine disr…[Mol Cell Endocrinol. 2009] – PubMed Result

An unique, new study found that maternal weight loss from bariatric surgery may improve cardiometabolic  risks in infants which is sustained into adulthood.Effects of Maternal Surgical Weight Loss in Mother…[J Clin Endocrinol Metab. 2009] – PubMed Result

 

Early infancy

Weight status in the first 6 months of life and ob…[Pediatrics. 2009] – PubMed Result

Predictors of body size in infancy Predictors of body size in the first 2 y of life: …[Int J Obes Relat Metab Disord. 2004] – PubMed Result

Parental feeding styles

Children from obese parents were more likely to have a preference for fatty foods, lower liking for vegetables and a more overeating type eating style than children with lean parents as well as a greater preference for sedentary activities. Food and activity preferences in children of lean …[Int J Obes Relat Metab Disord. 2001] – PubMed Result The picture of the obese mother using food for non-nutritive purposes may be a myth but there obese mothers may exercise less control. Parental feeding style and the inter-generational …[Obes Res. 2002] – PubMed Result Infants of overweight/obese mothers have higher energy intake Relationship between maternal obesity and infant f…[Nutr J. 2005] – PubMed Result Infants born to overweight/obese mothers have lower resting metabolic rate, higher BMI Lower energy expenditures in infants from obese bi…[Nutr J. 2008] – PubMed Result

Breastfeeding

Breastfeeding has long been considered protective against the development of obesity Association between infant breastfeeding and overw…[JAMA. 2001] – PubMed Result

But not everyone is convinced.Critical review of the World Health Organization’s…[Obes Rev. 2008] – PubMed Result and Breastfeeding and the risk of childhood obesity. [Coll Antropol. 2007] – PubMed Result

How breastfeeding might be protective has not yet been determined. Mechanisms underlying the association between brea…[Int J Pediatr Obes. 2009] – PubMed Result

Overweight/obese mothers may be less likely to breastfeed their children than normal weight mothers. A systematic review of maternal obesity and breast…[BMC Pregnancy Childbirth. 2007] – PubMed Result