A ‘smoking gun’ for weight loss

Smokers often hesitate to quit, as losing cigarettes usually means gaining weight. But maybe it doesn’t have to be this way. According to a new Weizmann study, this increase in weight may be connected to compounds produced by gut microbes. Identified in mice, these compounds may someday contribute to anti-obesity treatments for smokers and non- smokers alike.

Prof. Eran Elinav and his team in the Department of Systems Immunology examined mice which had been regularly exposed to cigarette smoke and fed a diet high in fat and sugar. They demonstrated that, despite this poor diet, the mice that “smoked” did not gain weight. However, when smoke exposure ceased (modeling the process of “quitting” smoking), the mice gained weight rapidly.

Some mice were given antibiotics after smoking cessation, thus depleting the microbiome—the community of bacterial species residing in the mouse gut. This treatment resulted in a lower weight gain, indicating that the bacteria wiped out by antibiotics are connected to the weight gain observed after the mice “quit” smoking.

To confirm this hypothesis, the scientists transferred microbiomes—taken from both “smoking” and “smoking cessation” mouse models—into mice completely lacking in gut bacteria and which had never been exposed to cigarette smoke.

All of the recipient mice gained weight when the microbiomes were transferred, but the most dramatic gain was seen in mice that received “smoking cessation” microbiomes. Meaning the process of smoking and then quitting had altered the gut microbes, which correlated with greater weight gain. The scientists then identified two molecules generated or altered by the smoke-exposed microbiome—dimethylglycine (DMG), which produces at heightened levels with smoke exposure; and acetylglycine (ACG), which produces at lower levels—and demonstrated that DMG and ACG levels mediate weight gain. When “smoking cessation” mice were fed a diet with limited DMG production, they didn’t gain weight. However, when given a DMG supplement, their tendency toward weight gain returned. On the other hand, when the scientists boosted levels of ACG, the mice failed to gain weight. Intriguingly, the DMG- and ACG-related impact on weight was also seen in non- smoking mice.

A preliminary study in 96 smoking and non-smoking humans suggests that molecular changes observed in the mouse microbiome may be relevant to humans as well. These findings could contribute to new strategies for weight loss—among current, former, and non-smokers.

Prof. Eran Elinav is supported by:

- Leona M. and Harry B. Helmsley Charitable Trust

- Belle S. and Irving E. Meller Center for the Biology of Aging

- Jeanne and Joseph Nissim Center for Life Sciences Research

-  Sagol Institute for Longevity Research

- Sagol Weizmann-MIT Bridge Program     

- Swiss Society Institute for Cancer Prevention Research

- Prof. Elinav is the incumbent of the Sir Marc and Lady

 - Tania Feldmann Professorial Chair of Immunology

- The Vera Rosenberg Schwartz Research Fellow Chair supports a staff scientist in Prof. Elinav’s lab