In obese subjects whose metabolic profiles were already abnormal, weight gain was associated with a significant worsening of their metabolic profiles.
The researchers, from Washington University School of Medicine in St. Louis, MO, recruited 20 obese participants who were asked to gain 15 lb in weight over several months. The findings of the study are published in The Journal of Clinical Investigation.
The researchers then studied how the gain in weight affected the participants' metabolism. Before and after gaining the weight, the participants' abilities to regulate blood sugar and liver fat were measured, as were their body compositions and sensitivities to insulin.
To gain weight, the participants ate at fast-food restaurants, under the supervision of a dietitian, at restaurants selected by the researchers on the basis of their accurate reporting of nutritional information and consistent portion sizes.
If the metabolic profiles of the participants were in the normal range when the study began, then they remained normal after these participants gained weight.
But the researchers observed that, in obese subjects whose metabolic profiles were already abnormal, weight gain was associated with a significant worsening of their metabolic profiles.
Senior investigator Dr. Samuel Klein, the Danforth Professor of Medicine and Nutritional Science and director of Washington University's Center for Human Nutrition, explains the finding:
"This research demonstrates that some obese people are protected from the adverse metabolic effects of moderate weight gain, whereas others are predisposed to develop these problems.
This observation is important clinically because about 25% of obese people do not have metabolic complications. Our data shows that these people remain metabolically normal even after they gain additional weight."
Key factors identified that distinguish normal and abnormal metabolisms
The researchers identified some factors that distinguished the metabolically normal obese participants from the participants with metabolic problems.
One of these key factors was the accumulation of fat inside the livers of people with abnormal metabolism - people with normal metabolism did not have these fat accumulations.
Also, the participants with normal metabolism expressed more genes that regulate the production and accumulation of fat than those with abnormal metabolism. This gene activity increased when the metabolically normal participants gained weight, but there was no increased activity in those with abnormal metabolism.
According to the authors, this suggests that the ability of body fat to increase and expand may protect some people from the metabolic problems that are traditionally associated with gaining weight.
"It's important to point out that once the study was completed, we enrolled all subjects in our weight-loss program to make sure they lost all of the weight they had gained, or more," says Dr. Klein
Next, the team will analyze fat, muscle and liver tissue in lean as well as obese people in order to better understand the mechanisms by which some individuals - and not others - are protected from metabolic problems.
Dr. Klein says the team hopes to solve whether it is genetics, specific dietary intake, physical lifestyle, emotional health or even gut microbes that influence whether obesity causes diseases in some people but not in others.