Weight gain after losing weight: Researchers find hormonal link

Melissa Eide

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Maintaining weight loss may be influenced by the levels of a particular hormone. Ivan Andrianov/Stocksy
  • Obesity is linked to many health conditions and is associated with the leading causes of death globally.
  • Attempts to lose excess weight through lifestyle changes are often thwarted by the fact that the majority of people who do manage to lose excess weight, regain it.
  • The role of hormones in this process is complex and understanding it could help to develop long-term treatments for obesity.
  • Higher levels of the hormone neurotensin have now been linked to better weight loss maintenance among people with obesity, offering a further clue on how rebound weight gain could be managed.

While many people with overweight or obesity are able to lose excess weight through lifestyle interventions such as diet and exercise, it has long been recognized that it is challenging for many to keep this weight off.

Obesity is considered an epidemic by the World Health Organization (WHO), as over 4 million people are dying, as a result, each year. It is believed a lot of these deaths could be avoided with weight loss. For example, a weight loss of 5-7% has been shown to prevent or delay the onset of type 2 diabetes.

Unfortunately, as many as 80% of those who have lost weight through diet and exercise regain all of the weight they originally lost. Historically this weight gain has been blamed on a lack of self-control or failure to adhere to weight maintenance regimes.

The latest research offers a new explanation: in individuals with obesity who have recently lost weight, a higher level of the hormone neurotensin could be linked to a better ability to maintain this weight loss.

Their findings have been published in the journal Metabolism.

One theory to explain why people experience rebound weight gain has been that of set-point weight, the idea that the body will return to a set weight despite weight loss or gain.

Dr. Mir Ali, bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center, Fountain Valley, C.A.explained to Medical News Today:

“The theory of set point weight is there is weight that your body wants to remain close to (give or take 5-10lb); many factors including age, genetics, sex, medical conditions and activity level can affect this set point.”

The mechanisms that might be behind this observation, are unclear, however.

Despite the rise in the number of people with obesity starting in the 1970s according to the WHO, the role of hormones in appetite regulation has only become apparent in recent decades. Ghrelin, a hormone that increases the drive to eat, was only isolated and identified in 1999. It is now known to regulate appetite, fat storage, and energy regulation. It also interacts with other hormones involved in fat storage and energy regulation such as insulin.

Previous research has shown that ghrelin levels tend to rise after weight loss following diet and exercise, and researchers have proposed this could be a cause of ‘rebound weight gain’. Conversely, levels of this hormone decrease after bariatric surgery, which has a lower rate of rebound weight gain than diet and exercise-based interventions.

The interaction between ghrelin and leptin, a hormone that regulates satiety and energy regulation over the longer term, was discovered less than 20 years ago in 2004. Since then, leptin resistance has been found to exist in people with obesity, making them less sensitive to its appetite-quelling effects.

More recently, attention has turned to another hormone called neurotensin, and its potential role in weight gain after weight loss. This hormone is produced in the brain and gut. Previous research has shown that neurotensin levels increase after bariatric surgery, much like other hormones that regulate energy expenditure and appetite.

Dr. Gina Leinninger, associate professor of physiology at Michigan State University who researches the regulation of energy and its contribution to obesity in humans told MNT:

“There has been growing interest in how neurotensin could modulate body weight. We knew from prior research that when animal models received neurotensin it could reduce their feeding and increase their locomotor activity— dual behaviors that could support weight loss.”

A group of researchers from Denmark has shown that in individuals who have recently lost weight, higher neurotensin levels after meals could be linked to how likely they are to maintain their weight. They also showed neurotensin levels decrease after weight loss in mice and people with obesity.

Researchers first put 9 obese mice on a calorie-restricted diet for 8 days and kept 8 obese mice on a normal diet to act as controls. After euthanizing the animals, the researchers took samples from four parts of the intestine— the duodenum, jejunum, ileum, and proximal colon—to look at the levels of neurotensin expressed in those areas.

The calorie-restricted diet in mice aimed to induce weight loss similar to that observed in the 8-week human study.

The researchers found the mice that had their food restricted had significantly reduced neurotensin concentrations in the jejunum part of the small intestine.

Next, researchers looked at the effect of a very low-calorie diet regime of around 800 calories a day for 8 weeks on a cohort of 42 obese patients. Participants lost an average of 12.3 kg following this intervention. At the end of this 8-week period, participants underwent testing to observe how their leptin, insulin, ghrelin, and neurotensin levels changed in the three hours after a meal.

Researchers then instructed this cohort to follow a calorie-restricted diet (600 calories less than their daily need), for a further 52 weeks.

To analyze the impact of hormones on weight loss maintenance, researchers analyzed findings for a subcohort of participants, from both groups, those who had lost over 3% weight during the maintenance period and those who had regained 5% or more of their initial weight loss.

They found that those who had initially shown a higher level of neurotensin in the three hours after a meal after the initial 8-week weight loss phase were more likely to have lost additional weight in the maintenance period.

Leptin, insulin, and ghrelin levels were not significantly different in either cohort.

“The Metabolism paper is the first to link changes in circulating neurotensin to better/ sustained weight loss outcomes in humans, and suggest that (in the future), modulating the neurotensin system might be useful to help support and/or optimize weight loss. However, of course, there is much more to understand before that goal is achievable!”
— Dr. Leinninger

Dr. Leinninger’s own research had been looking at which parts of the brain neurotensin affects, and if this plays a role in energy regulation and obesity. The next steps in research will center around that.

“The next big questions are how neurotensin can control weight, and more specifically, where in the body it works. My lab has been exploring how and where in the brain neurotensin can modulate body weight and we have some good leads!” she said.

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