According to a new UCLA study, it is not just what you eat that widens your waistline; it is also due to your DNA. They have discovered that body-fat responses to a typical fast-food diet are determined to a large extent by genetic factors. In addition, they have identified several genes that might control those responses. The findings were published online on January 8 in the journal Cell Metabolism; they will appear January 9 in the print version.
The researchers note that their study is the first of its kind to detail metabolic responses to a high-fat, high-sugar diet in a large and diverse mouse population under defined environmental conditions. Although they used an animal model, they assert that it should closely simulate what is likely to occur in human populations. In addition, the investigators found that the amount of food consumed contributed only modestly to the degree of obesity.
“Our research demonstrates that body-fat responses to high-fat, high-sugar diets have a very strong genetic component, and we have identified several genetic factors potentially regulating these responses,” explained first author Dr. Brian Parks, a postdoctoral researcher at the David Geffen School of Medicine at UCLA. He added, “We found that obesity has similar genetic signatures in mice and humans, indicating the mice are a highly relevant model system to study obesity. Overall, our work has broad implications concerning the genetic nature of obesity and weight gain.”
The US and many other nations is currently experiencing an obesity epidemic. The dramatic increase in obesity over the past few decades has been significantly associated with an increase in obesity-related conditions such as type 2 diabetes, heart disease, and cancer. High-calorie diets containing high levels of fat and sugar, along with sedentary lifestyles, have been considered the most significant environmental factors contributing to this epidemic; however, the new research demonstrates that body-fat responses to food are strongly inherited and linked to our DNA.
During the two-year study, researchers measured obesity traits, adipose (fat) tissue, global gene expression, and intestinal flora (normal intestinal bacteria) in response to a high-fat, high-sugar diet in more than 100 inbred strains of mice. They identified 11 genome-wide “regions” associated with obesity and fat gain due to high-fat, high-sugar intake. Several identified regions overlap with genes identified in human studies. For the study, the mice were placed on a normal diet for the first eight weeks of life and were subsequently switched to a high-fat, high-sugar diet for eight weeks.
Dr. Parks explained, “We measured the change in fat dynamically, at five different points following a high-fat, high-sugar feeding, providing strong evidence for a genetically controlled body-fat set-point. Our use of inbred mice strains also enabled detailed analysis of the relationship between obesity traits, gene expression, intestinal flora and diet.”
The dietary responses of the mice, as assessed by the body-fat percentage increase during high-fat, high-sugar feeding, varied widely among the strains; increases in body-fat percentage ranging from 0% to more than 6005 in the various strains of mice. Most strains responded during the first four weeks of the high-fat, high-sugar feeding and did not accumulate additional fat during the remainder of the study. The researchers note that this suggests an upper body-fat set-point whereby continued gain in body fat is resisted by genetic mechanisms.
Additionally, “We observed high heritability of about 80% for body-fat percentage across the study timeline,” noted principal investigator Dr. Jake Lusis, a professor of medicine and human genetics and of microbiology, immunology and molecular genetics at the Geffen School of Medicine. He added, “Changes in body-fat percentage after high-fat, high-sugar feeding were also highly heritable, suggesting that dietary responses are strongly controlled by genetics.”
The authors noted that their results are consistent with the inheritance of body mass index (BMI) and obesity in humans and emphasize the importance of genetics in controlling obesity. They explained that overconsumption of high-calorie, high-sugar food is an important factor contributing to the obesity epidemic; however, they stress that food consumption is only one of many environmental factors that affect obesity.