Possible weight loss drug from smoking study

Many people lose weight when they start smoking cigarettes; indeed, back in the 90s, many fashion icons seemed to exist on a diet of coffee and tobacco. Unfortunately, the reverse is also true - when people quit smoking, they very commonly put on weight: up to 10kg in a year, in fact. And this weight gain is one of the big reasons why many smokers are reluctant to give up. Now a team of microbiologists at Israel’s Weizmann Institute of Science have been using mice to try to figure out exactly what’s happening inside the body that causes this weight gain. And in doing so, they may have just invented a new weight-loss drug, as Sally Le Page heard from Elan Elinav...

Eran - We can control the amount of smoke that mice actively are exposed to, but once we stop their exposure to smoking, they put on a lot of weight within a very short period of time.

Sally - And is this just because they are hungrier so they're eating more food?

Eran - No. This was one of the first surprises that we encountered in this study. We found that they were gaining lots of weight but were not eating more or changing their exercise behaviours. Which was a very big mystery.

Sally -
But we all know that the way that people gain weight is because they either eat more or exercise less. So what's going on?

Eran - This was what we knew until 10 or 15 years ago, but we've since learned that there is a third mechanism and this is called 'energy harvest'. Which is the capacity of our body to extract different amounts of energy from a given type of food. Now we know that this energy harvest capacity is at least partially controlled by the activity of the microbes that reside within our gastrointestinal trial.

Sally - Okay. So you can eat exactly the same food, but one person absorbs more of the energy and the other person poops out more of the energy?

Eran - Exactly.

Sally - And you mentioned the microbiome, do mice also have a gut microbiome like humans do?

Eran - They do indeed. It is up to 90% similar to the one we observed in humans.

Sally - And how can bacteria and microbes in our gut change how much energy we get from our food?

Eran - There are many different ways by which our microbes can impact human health, but they can also secrete thousands of small molecules, which we call 'metabolites', into our bloodstream.

Sally - Coming back to this smoking and weight gain, are these bacteria producing chemicals that make us humans extract more energy from the food, or is it the gut bacteria themselves that are extracting more energy from the food?

Eran - That's an excellent question. The surprising result was that we found that these gut bacteria are actually changed and modified both in their composition and their behavior following the exposure of mice to cigarette smoke. What we've discovered was that two of these molecules, two of these chemicals that are secreted in an altered fashion by these gut microbes, can explain the dramatic tendency of mice to develop weight gain when they stop being exposed to smoke.

Sally - Why do these microbes want their host to absorb more energy from the food when they experience the chemicals from smoke?

Eran - When animals or humans are exposed to cigarette smoke. Because of the chemicals introduced through cigarette smoke, they tend to lose a lot of weight. The microbes, as our internal partners, try to reverse this tendency by increasing the secretion of molecules at our end and increasing the weight back.

Sally - Oh, bless. So our little gut microbes are trying to protect us from starvation when we are just trying to drop a dress size. I suppose the big question that a lot of smokers will be wondering is how long does this microbiome effect last after someone stops smoking? Because of course, weight gain isn't good for your health, but then neither is smoking. So if someone is to quit smoking, is that it? Have they doomed themselves to putting on more weight forever?

Eran - You know, we can only answer this question at this point in mice. Once you stop smoking, these bacteria are there to stay for many months. Whether this is the case in humans, we don't know. But the encouraging news, is that once we've discovered how the microbes induce weight gain and identified the two molecules that contribute to this tendency, we can now intervene during the smoking cessation period and either supplement mice or humans with the molecule that induces weight reduction, or block the activity of the molecule that induced weight gain. And by this, we can help people stop smoking without paying the price in terms of their weight gain.

Sally - So potentially you could get a pill that you swallow and it kind of knocks out the chemical causing this weight gain so that people won't have weight gain. I mean, that sounds amazing. Would that work with weight gain, not associated with quitting smoking?

Eran - We asked ourselves this exact question. Now that we've identified the bioactive molecules, we could give them to mice that are suffering from obesity, even in the non-smoking context. These mice are obese because of other reasons and they were never exposed to smoke. When we gave the weight reducing molecule to obese mice, they developed a quite dramatic weight reduction and improvement in metabolic parameters.

Sally - That is a massive discovery. I suppose it's like telling your gut microbes, "Don't worry, I'm not starving. I am just trying to lose a dress size. Don't worry about me. You don't need to keep me fat. We're not gonna die."

Eran - Exactly. And to quench our curiosity, we've even gone into humans and we tried to measure in smokers or in people that never smoke the same chemicals and the same microbes that we discovered in mice and to a large extent, the changes that we've observed in smoking humans were very similar to the ones that we've observed in mice. Which encourages us that maybe, and this will be followed up in clinical trials, some of the concepts that we discovered here in mice could be also applicable in humans.