Clarifying the Obesity Genetics Picture

December 13th, 2012 No comments »

Obesity has always been known to carry a strong genetic component. At first, there was hope of finding “the gene.” This turned out to be a flawed strategy as many genes were identified which affected body weight and body weight distribution. In a new study, a team using genome-wide association studies (GWAS) studied extreme obesity cases and never-overweight controls as well as families segregating extreme obesity and thinness. They found 16 genome-wide significant signals with the FTO gene being the strongest signal. The second most powerful signal was the MC4R gene. Adding total body weight, waist circumference and waist to hip ration, they found a strong signal for the NRXN3 gene. The researchers state, “The results therefore strongly suggest that FTO and MC4R might be the only two major-effect genes for obesity with common variants in population of European ancestry.” PLOS ONE: Genome-Wide Association Study on Obesity


It’s not about Western Lifestyle!

September 26th, 2012 No comments »

Herman Ponzer of the Department of Anthropology at Hunter College and colleagues have challenged one of the major assumptions in current thinking about obesity. The assumption is that Western lifestyle differs markedly from those of our hunter-gatherer ancestors and that these changes are responsible for our current obesity epidemic. To look at this Ponzer and colleagues studied daily energy expenditure of the Hadza foragers. The Hadza live in a savannah-woodland environment in Northern Tanzania. It is believed that the lifestyle of the Hadza are similar in critical ways to our Pleistocene ancestors. Hadza women gather plant foods; while the men engage in hunting. 95% of their calories come from wild foods including tubers, berries, game, baobab fruit and honey. The researchers expected that the Hazda would have lower body fat than Western populations and that, with their natural diet and lack of mechanization, they should expend more energy than individuals living in market economies with comparatively sedentary lifestyles and more energy dense diets.

Surprise! The authors state, “Contrary to expectations, measures of TEE (total energy expenditure) among Hadza adults was similar to those in the Western (U.S. and Europe) populations.” Because the Hadza are smaller than Westerners, their energy spent on their basal metabolic rate (BMR) was smaller than for Westerners. According to the researchers, “ Measurements of TEE among Hadza hunter-gatherers challenge the view that Western lifestyles result in abnormally low energy expenditure, and that decreased energy expenditure is a primary cause of obesity in developed countries. Despite higher PAL (physical activity level) and dependence on wild foods, Hazda TEE was similar to Westerners and others in market economies. Further, while Hadza differed from Western populations in body fat percentage, variation in adiposity both within and between populations was not correlated with PAL nor with TEE. The lack of correspondence between TEE, PAL, and adiposity in our Hazda and comparative samples is consistent with previous DLW (doubly labeled water) studies in Western populations. The similarity in TEE among Hadza hunter-gatherers and Westerners suggests that even dramatic differences in lifestyle may have a negligible effect on TEE, and is consistent with the view that differences in obesity prevalence between populations result primarily from differences in energy intake rather than energy expenditure…Data on hunter-gatherer TEE provide additional perspectives on Paleolithic humans and on the origins of farming. While the lifestyle of late Pleistocene hunter-gatherers was no doubt highly active as seen in foragers today, our results suggest that their daily energy requirements were likely no different than current  Western populations…TEE is remarkably similar across a broad, global sample of populations that span a range of economies, climates and lifestyles. Not only is TEE statistically indistinguishable between Western, foraging, and farming population levels. We hypothesize that TEE may be a relatively stable, constrained physiological trait for the human species, more a product of our common genetic inheritance than our diverse lifestyles.”. They cite another study pointing to the body’s complex physiological responses to dieting and weight loss support this view PubMed_Hunter Gatherer Energetics and Human Obesity

This is not the first study making this observation. Ramon A. Surazo-Arizu of Loyola University Medical School and colleagues studied the rise of obesity in three countries: Jamaica, Nigeria and the United States. They found that women in Nigeria and the US had higher weight gains than men but the reverse was true for Jamaicans. They write, “The steep trajectory of weight gain in Jamaica, relative to Nigeria and the US, is most likely attributable to the accelerating effects of the cultural and behavioral shifts which have come to bear on transitional societies.” The three countries span economic development from highly developed (U.S.) to middle-income (but stagnant in Jamaica’s case) to low-income (Nigeria). The average weight gain was .43 kg/year in Nigeria, 1.28 kg/year in Jamaica and .38 kg/year in the US. The researchers observed, “The prevalence of obesity was lowest in Nigeria, although during this time period participants in that rural community were gaining about as much weight as those followed in the U.S…Over the last 10-15 years societies as geographically and culturally distant as Barbados, Russia, Kuwait, and Japan have all experienced rapid increases in relative weight, affecting both children and adults. In the US the shift in the BMI trend slope occurred in the mid-1980’s and a 5-fold increase in the rate of change/year has been observed subsequently. Even Norway – with its historically low obesity rates and high participation in leisure time physical activity – experienced an abrupt up-turn around 1990. Clearly some “common source exposure” is shifting the population distribution of weight right-ward and virtually all segments of the societies that participated in the world economy are being affected. While it is assumed that lifestyle changes related to the growing consumer economy are the driving force it has been difficult to define and quantify the specific factors…Although Jamaica has undergone rapid cultural changes over the last 20 years, accompanied by a decrease in the rural population, it has experienced stagnating or negative economic growth. While accurate economic data are difficult to obtain, it is also unlikely that average Nigerians have seen any substantial increase in their material standard of living over the last 2 decades. Thus, the lifestyle changes required to fuel weight gain do not require general economic development, and instead may reflect the penetration of market-based consumption patterns into stagnating or declining economies. These observations suggest that it is the character of social development, not necessarily the level of economic activity per se that is driving the combined obesity-diabetes epidemic in many poor and middle-income countries.” PubMed: Rapid increases in obesity in Jamaica, compared to Nigeria, US

Our Genes Are Changing: New Evidence

August 23rd, 2012 1 comment »

As readers of these pages know, I always react when people, in discussing obesity, dismiss genetics as a cause with the statement to the effect, ‘our genes just don’t change.’ On other pages, I recite evidence that this just isn’t true. Our genes do change. I also notice that you never hear a genetics expert make this claim. And for a good reason, our knowledge of genetics changes every week.

Now comes a new study using genomic databases from Iceland. The study of 78 trios of mother, father and child, looking for mutations in the child’s genes which were not present in either parent and therefore must have arisen spontaneously in the egg, sperm or embryo. Fathers passed on nearly four times as many new mutations as mothers, 55 v. 14. The older the father, the greater the number of mutations. Most of the mutations may be harmless but some are linked to conditions like autism and schizophrenia. NatureNews:Fathers bequeath more mutations as they age

Maternal obesity and metabolic conditions have been linked to autism in their offspring PubMed: Maternal Metabolic Conditions and risk of autism. Likewise, schizophrenia has been linked to obesity, diabetes and inflammation PubMed: Schizophrenia, metabolic syndrrome and inflammation

Bottom line: while the increasing age of the father may be relevant for autism research, the point for obesity genetics may be that both mothers and fathers pass on spontaneous mutations to their child. Our genes are changing.


New studies expand understanding of role of genes

May 29th, 2012 No comments »

Two new studies are shedding more light on the role of genetics in obesity. The first, from Lombard and colleagues at the University of the Witwatersrand in South Africa, looked at obesity in South African adolescents, and found  4 SNPs (single nucleotide polymorphisms) were individually significantly associated with body mass index (BM). Together, the four SNPs account for 2.1% of the variation in BMI. Each risk allele was associated with an estimated average increase of 2.5% in BMI. PubMed: Appetite regulation genes BMI association.

The second study, by Williams and colleagues at Uppsala University in Sweden, discovered 33 new genes associated with human obesity. The majority can be traced to distant species, such as D. melanogaster or the fruit fly and C. elegans, a roundworm. The authors speculate that these findings may identify new pathways for obesity drug development. PubMed: What model organisms and interactomics can reveal about genetics of human obesity


Could obesity be contributing to rise in Autism?

May 19th, 2012 No comments »

Obesity is known to contribute to birth defects. Now comes a new study linking obesity, type 2 diabetes and hypertension to autism spectrum disorders and developmental delays. More

Genetic Variations Affect Weight Loss, Regain, Eating Behavior

May 1st, 2012 No comments »

The Diabetes Prevention Program (DPP) is a highly publicized study comparing lifestyle intervention against metformin in preventing type 2 diabetes. It has been widely used by public health authorities to promote lifestyle changes over drugs in addressing obesity and type 2 diabetes. Delahanty LM and colleagues looked at genetic polymorphisms for an effect on short term and long term weight loss and weight regain. They found that the Ala allele at PPARG (think of this as the longitude and latitude for a gene variation) was associated with short term and long term – weight loss regardless of treatment. This study adds to the literature that genetic information can help identify those who can are more likely or less likely to benefit from intervention. PubMed:Genetic Predictors of weight loss, regain DPP

In a another trial, Look AHEAD, another obesity related risk allele at FTO rs1421085 significantly predicted more eating episodes per day. Variants within BDNF were significantly associated with more servings of dairy, meat, eggs, nut and beans. Another allele was associated with a significantly lower percentage of energy from protein. PubMed:Genetic alleles and dietary intake in Look AHEAD trial


New View on the Origins of Our Obesity Predicament

December 24th, 2011 No comments »

As readers know, there is a certain disconnect about when the obesity    epidemic began. Personally, I am quite persuaded that the historical record for the increase in human weight and height (the two parts of the BMI formula) goes back at least 350 years. (See, The Techno-physiological Revolution). On the other hand, something seemed to happened in the United States around the 1970s to send the rates skyward. There are no end of theories, all of which have some plausibility. So now comes Melinda Sothern, a well-respected and highly published obesity researcher, with a new look at mothers in the 1950’s. (Ouch! That’s a little close to home.) Her thoughts in this article do meet up with current research on genetic and, especially, epigenetic factors influencing the development of obesity. 

Many knowledgeable researchers have avoided going into this territory, not because of the science but because of the fear of being blamed for blaming mothers. This is not an inconsequential factor as parents may defer medical care for fear of being blamed for their child’s weight problems. (See the Cleveland obese boy incident.)

Sothern’s experiences and scientific credibility gives impetus to seriously consider her thoughts on the origin of our current predicament, given in this article in The Republic, ’50s women may have triggered obesity epidemic | The Republic

Genetics and Treatments

December 20th, 2011 No comments »

The Diabetes Prevention Program (DPP) is regarded as a hallmark of behavioral intervention in the treatment of adult obesity. Now comes a paper from the DPP Study Group, as well as drug therapy via metformin. It recognizes that genetic factors affect the success of participants in achieving and maintain weight loss. Genetic Predictors of Weight Loss and Weight R… [Diabetes Care. 2011] – PubMed – NCBI