In a study that could lead to development of new treatment for "recurrent" or "yo-yo" obesity, researchers have found that intestinal microbes -- collectively termed the gut microbiome -- play an important role in post-dieting weight gain.
Following a successful diet, many people are dismayed to find their weight rebounding. Worse still, the vast majority of recurrently obese individuals not only rebound to their pre-dieting weight but also gain more weight with each dieting cycle.
In experiments with mice, the researchers at Weizmann Institute of Science in Israel found that after a cycle of gaining and losing weight, all the mice's body systems fully reverted to normal -- except the microbiome.
"We've shown in obese mice that following successful dieting and weight loss, the microbiome retains a 'memory' of previous obesity," said researcher Eran Elinav.
For about six months after losing weight, post-obese mice retained an abnormal "obese" microbiome, reported the study published in the journal Nature.
"This persistent microbiome accelerated the regaining of weight when the mice were put back on a high-calorie diet or ate regular food in excessive amounts," one of the researchers Eran Segal said.
"By conducting a detailed functional analysis of the microbiome, we've developed potential therapeutic approaches to alleviating its impact on weight regain," Segal noted.
By combining genomic and metabolic approaches, the researchers identified two molecules driving the impact of the microbiome on regaining weight.
These molecules -- belonging to the class of organic chemicals called flavonoids that are obtained through eating certain vegetables -- are rapidly degraded by the "post-dieting" microbiome, so that the levels of these molecules in post-dieting mice are significantly lower than those in mice with no history of obesity.
The researchers found that under normal circumstances, these two flavonoids promote energy expenditure during fat metabolism.
Low levels of these flavonoids in weight cycling prevented this fat-derived energy release, causing the post-dieting mice to accumulate extra fat when they were returned to a high-calorie diet.
Finally, the researchers used these insights to develop new proof-of-concept treatments for recurrent obesity.
They supplemented post-dieting mice with flavonoids added to their drinking water.
This brought their flavonoid levels, and thus their energy expenditure, back to normal levels. As a result, even on return to a high-calorie diet, the mice did not experience accelerated weight gain.
"If the results of our mouse studies are found to be applicable to humans, they may help diagnose and treat recurrent obesity, and this, in turn, may help alleviate the obesity epidemic," Elinav said.