Teen Skepchick Interviews: Diana Williams, Follow-up Questions

This post is part of the Teen Skepchick Interviews series, where TS writers talk with amazing women scientists and skeptics about life, the universe, and everything.

Our interview with Dr. Diana Williams, who researches neuroendocrine control of food intake, body weight, and metabolism (see part 1 here, and part 2 here), elicited some follow-up questions in the comments and on Facebook. So today, you are interviewing Dr. Williams. Read on to hear what she has to say about leptin-therapy research, whether leptin levels ever normalize after weight loss, muscle vs. fat, whether processed foods contribute more to weight gain, and more.

Follow-up Teen Skepchick questions:

From Rebel 16:

I have a couple of questions about the “keeping it off” aspect.

Part 1 mentioned leptin levels as a factor in keeping weight on despite attempts to reduce it. Has there been any research into using some form of artificial supplement to help normalize leptin levels in dieters?

Yes, this and other possible therapeutic roles for leptin have been major topics of investigation. When leptin was first discovered in the mid-1990s, it was proposed as an obesity therapy right away. Back then, the idea was that you would simply inject obese people with leptin and it would make them lose weight. This actually works extremely well in people who are obese because they have a gene mutation that renders their fat cells incapable of making leptin. For that very small population, leptin therapy is great, but it was not so successful for others.

One reason is that people with a large amount of fat already have plenty of leptin, and the leptin signal to the brain is actually less effective in that situation. So simply adding more does not do much. Since that time, we came to understand that the body is really paying attention to falling leptin levels as an emergency signal. In that context, it seems reasonable that you might be able to do “leptin replacement” therapy in weight-reduced people. There, the idea would be that the leptin therapy isn’t causing weight loss, but preventing those compensatory responses that cause regain of lost weight.

Rosenbaum and colleagues examined this hypothesis in small groups of people and found that leptin replacement therapy did reverse the effects of weight loss on energy expenditure, muscle work efficiency, and some other metabolic variables. They’ve also shown that leptin replacement in weight-reduced people can reverse the usual weight-loss-induced increase in brain activation in response to pictures of food. These results would seem to support the suggestion that leptin replacement therapy would at least help people maintain some of their weight loss. However, these experiments were performed with people living in the hospital ingesting only a controlled amount of liquid diet that was carefully calibrated to maintain their 10% weight loss. So we cannot make assumptions about what benefit leptin therapy may have in free-living people based on these results.

The first of those studies was published ten years ago. Pharmaceutical companies have been working to develop leptin-based obesity therapies since the mid-1990s, so it would be very surprising if they haven’t already tried this approach by now. There may be technical barriers—e.g., practical drug-delivery issues, immune reactions to leptin injections. But another factor is that leptin replacement will not reverse all the effects of weight loss. Leptin is important, but it is one of many hormones that change with weight loss, and not all compensatory responses are driven by the fall in leptin levels.

For example, another relevant hormone is ghrelin, made by the stomach and intestine. Ghrelin is sometimes called a “hunger hormone” because it strongly promotes eating. Ghrelin levels go up at times when we anticipate eating, such as right before mealtime if you’re on a routine schedule, and ghrelin goes back down as we begin to eat, and food makes its way through the digestive tract. Ghrelin levels also go up with food restriction and weight loss, and it’s hypothesized that this increase in ghrelin levels after weight loss is one of the factors that promotes the regain of that lost weight. Leptin does not directly control ghrelin levels, so leptin replacement therapy may not impact this response to weight loss. And again, this is just one example. Many scientists in this area believe that combination therapies—drugs that target more than one hormone system at the same time—will be more effective than single-target treatments.

Also, mention was made [in your previous interview] that even a year after weight loss, leptin levels can remain lower than normal. Do these levels ever normalize, or will your body fight for the rest of your life to return to a heavier weight?

Leptin circulates in proportion to body fat, so we would expect leptin levels to always be lower in a weight-reduced person than they were before that person lost the weight. The weight-reduced individual’s fat will only make more leptin if the person gains fat. I’m not aware of any studies that have looked at leptin levels in humans for more than one year after weight loss, but all indications are that the compensatory responses to weight loss persist.

For example, people in the National Weight Control Registry (NWCR) who have maintained weight loss for many years still report that they eat less and exercise more than non-weight-reduced people of the same size. If those compensatory responses to weight loss lessened over time, then they would be able to maintain the weight loss with “normal” eating and activity levels, but that appears not to be the case. Surveys of these very long-term weight-loss maintainers suggest that they do find their food restriction and high exercise levels easier to live with the longer they do it, as these become automatic habits, but it appears that these individuals will indeed be working against the physiologic drive to regain the weight for the rest of their lives.

From Facebook:

How much of weight loss or weight gain, particularly in women, is attributed to losing or gaining muscle? Does the BMI take muscle into account as part of the weight it measures?

BMI, body mass index, is simply weight in kilograms divided by height in meters squared. No other information is included. BMI does not measure fat or muscle, and although it is correlated with fat mass (i.e., many people with high BMIs also have a lot of body fat), BMI alone tells you nothing about a person’s body composition. It’s not uncommon for muscular athletes to be labeled as obese when they actually have relatively low body fat.

This hasn’t been extremely well studied, but it’s been estimated that about 75% of lost weight due to dieting is fat while 25% is muscle, and even more muscle is lost in more severe starvation situations. Resistance training or aerobic exercise can mitigate some of that muscle loss. Because women have very low testosterone levels compared with men, exercise typically does not increase muscle mass a great deal in women. The maximum possible muscle mass that one can achieve varies widely across individuals, but women who gain really large amounts of muscle without the use of anabolic steroids are going to be those who have the genetic predisposition to be highly muscular plus spend a lot of time at the gym lifting weights. It’s worth noting that strength is not equivalent to muscle mass, and women can increase strength quite a bit without seeing large increases in muscle mass.

Is there a difference between processed foods and whole foods when it comes to gaining weight, as in gaining more weight faster or having more trouble maintaining if you eat processed foods?

It’s difficult to answer this question because the term “processed food” has no universal meaning. We probably all agree that cheese doodles and Twinkies are processed food, but should we include any food containing refined sugar or white flour? Or does processed food mean packaged food containing preservatives, as opposed to home-cooked from fresh ingredients?

We know that people who report that they eat fast food frequently or drink a lot of high-sugar beverages like soft drinks and juices tend to have higher body weights than those who eat and drink less of that stuff. But that may be because the fast food eaters and soda drinkers consume more calories. Trans-fats, another category of ingredient that we can probably all agree counts as “processed,” are now banned in many locations because of the evidence that they contribute to cardiovascular disease. However, trans-fats seem to have at most a tiny effect to increase body weight, and some studies have found no effect at all.

These foods and drinks do seem to have negative effects on health—cardiovascular disease, diabetes—and it’s hard to imagine that overeating green beans, for example, would be just as unhealthy. Still, it’s not clear that something about the processing and production of these foods is a problem above and beyond the fact that people like to consume a lot of this stuff. Without a doubt, it is far easier for most people to eat 1,000 kcal worth of cake than 1,000 kcal of apples. When consuming energy-dense foods, it’s also easy to underestimate how much one has eaten. That in itself is interesting and may be related to the taste and palatability of those processed energy-dense foods, or their ability to activate our brain reward systems to a greater degree than less processed food.

People who consciously avoid processed foods have to make some effort, because this stuff is so ubiquitous today. Those willing to make such an effort are likely to care about their health and engage in other health-promoting behaviors, and that could also contribute to any differences that we may observe. Moreover, there is no doubt that people can lose weight on diets that include highly processed food (e.g., the “convenience store diet” that gained internet fame last year: “Twinkie diet helps nutrition professor lose 27 pounds” ). That doesn’t mean that junk-food diets are healthy, only that eating a low-calorie diet can result in weight loss no matter what the source of those calories.

Do the studies, such as the National Weight Control Registry, take into account diabetes or similar issues that might affect weight gain and loss? Does diabetes tend to change the way people gain or lose weight?

I’m not aware of any publications from the NWCR or other research on long-term weight-loss maintenance that specifically compares people with and without diabetes or other metabolic disorders. But yes, both type 1 and type 2 diabetes mellitus can affect weight, and in particular, successful medical treatment of both types of diabetes can cause weight gain.

In type 1 diabetes, the problem is that the pancreas fails to produce the hormone insulin. Insulin is required for transport of nutrients into the cells of our bodies, so lack of insulin is a serious problem. Insulin is also required for fat deposition. So people with type 1 diabetes often experience unexplained weight loss before they are diagnosed, because they are unable to store the energy that they eat. That energy circulates in the blood, so we see high blood-glucose concentrations, and it’s excreted in urine. Once they get on insulin treatment, they can now “put away” those nutrients into their bodies’ cells, and this promotes fat gain. More successful management of blood glucose is related to increased fat mass, so those individuals in the best shape are those gaining the most fat. For this particular population, this weight gain does not correlate with increased cardiovascular risk or mortality, so although it is undesirable for a lot of people, it’s not really a health concern.

Type 2 diabetes is a different situation. There, the pancreas is producing insulin but that insulin fails to work properly. At first, the pancreas just makes more insulin to compensate, but eventually even the maximum level of insulin that the pancreas can produce is not enough, and that’s when we see high blood-glucose concentrations. If left untreated, a person with type 2 diabetes will also start losing weight just like we see in type 1 diabetes, but it would take a while to get to that point.

Typically, when a person is diagnosed, diet and lifestyle changes are recommended and the person will start some sort of medication, often a drug that increases their sensitivity to insulin so that their insulin will start working better. Several of the most commonly used insulin-sensitizing drugs are known to cause weight gain. Eventually, most people with type 2 diabetes also need to take insulin, because their own pancreatic insulin-producing cells begin to fail, and as I explained earlier, insulin also promotes fat gain. So, many people with type 2 diabetes find themselves in the unfortunate position of trying to lose weight while taking medication that will prevent that from happening.

When you talked about the people who had successfully kept off the lost weight, you mentioned that they stopped eating foods (like French fries and cheese) entirely. How is that different from dieting? Doesn’t that show that some diets do work?

Yes, several studies have reported that many of the NWCR members, people who have maintained a 30-pound weight loss for at least one year, restrict their intake of certain foods. The details of their diets vary (e.g., most do low-fat, but some do low-carb), and not all of the registrants take that approach. It’s important to keep in mind that while the characteristics and strategies of the members of the NWCR are interesting, we cannot say with certainty whether or which of their behaviors are actually causally related to their weight-loss maintenance. This is descriptive information, not an experimental analysis of what behaviors cause maintenance of weight loss.

The NWCR subjects are a self-selected minority population, not a representative sample of all people who try to lose weight. In study after study, it’s been found that only 5–20% of dieters maintain a significant weight loss for up to five years after the initial loss. I would not say that a treatment with this success rate “works.” This means that diets fail for 80–95% of people, and these are the very same diets and approaches that many of the members of the NWCR used.

So when we look at the habits of NWCR members, we’re looking at a group that had a pretty unusual outcome. Their existence does show that maintenance of diet-induced weight loss is possible, and it may be the case that some of the 80-95% of the population that regain all or most of their lost weight could keep at least some of it off if they behaved more like NWCR members. But it’s also a real possibility that individual differences in the neurohormonal systems that control body weight render some people more and others less likely to regain lost weight.

When I mentioned these studies to a relative, she said that she’d kept off more than 100 pounds for more than five years and she doesn’t fit the profile of exercising an hour a day (although she does exercise), doesn’t restrict calories (but doesn’t eat many carbs and eats nutritiously). Does this prove the findings of the National Weight Control Registry wrong?

No, your relative is firmly within the range of what the NWCR reports about its members.  Remember, we’re talking about thousands of people here—there’s a lot of variability. Many consciously restrict their caloric intake, but not everyone. “Eating nutritiously” and limiting carbohydrate intake is food restriction, even if this person is not counting every calorie. As I noted earlier, people report that they find it easier and more automatic to eat less and maintain a low-variety diet the longer they maintain their weight loss, so your relative may be doing this without recognizing it for what it is. Exercise also varies widely among NWCR members, with 9% reporting that they don’t exercise at all. On average, these people are getting in a great deal of physical activity, but there is a large range. These are not hard and fast rules that one must follow in order to maintain weight loss. This is descriptive information about a population that has been able to do so.

What do you think about the idea that belly fat is especially dangerous to your health? Any real science to that?

Yes, there is actually a kernel of truth to that, but I think the message is not always clearly delivered. The issue is what people understand the term “belly fat” to mean. There is now a fair amount of evidence to support the idea that higher visceral fat mass is related to higher risk for diabetes and heart disease. Visceral fat is inside the abdominal cavity surrounding the internal organs, whereas subcutaneous fat is under the skin and on top of muscle. Women tend to have more subcutaneous fat than men, while men have more visceral fat, and this is determined by our gonadal hormones (e.g., estrogens, testosterone). After menopause, women gain more visceral fat, and coincidentally, risk for diabetes and heart disease goes up.

An interesting thing about fat is that not all fat in the body is the same. Visceral and subcutaneous fat have different sensitivities to various hormones, and they secrete different amounts of hormones themselves. A person with a large visceral fat mass will often have the “beer gut” look, where he/she has a rounded belly but it feels hard and solid because there’s a thick layer of abdominal muscle right under the skin, and the fat is beneath that muscle. Compare that to subcutaneous fat, which is the softer, squishier look we are more accustomed to thinking about. Of course you can have lots of subcutaneous fat in the belly area, but that is not the more worrisome kind of fat. I suspect that when people see the “dangerous belly fat” stories, they interpret that to mean fat anywhere in the belly area, which is not accurate.

Disclaimer: No statements made in this interview should be taken as medical advice.

Dr. Diana Williams received her PhD from the University of Pennsylvania Department of Psychology in 2003, and trained as a postdoctoral fellow at the University of Washington School of Medicine, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, from 2003-2008. In 2008, she joined the faculty of Florida State University as an Assistant Professor in the Department of Psychology and Program in Neuroscience. Her laboratory focuses on the neural and endocrine control of food intake and body weight.


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Image credit: Photographs by Daniel Lobo, PinkShot, Ricky Rhodes, and Vee Dub.

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Melanie Mallon

Melanie Mallon

Melanie is a freelance editor and writer living in a small town outside Minneapolis with her husband, two kids, dog, and two cats. When not making fun of bad charts or running the Uncensorship Project, she spends her time wrangling commas, making colon jokes, and putting out random dumpster fires. You can find her on Twitter as @MelMall, on Facebook, and on Instagram.

1 Comment

  1. January 12, 2012 at 4:44 pm —

    Thanks for the great articles and excellent followup, Melanie and Dr. Williams! You’ve certainly cleared up several of my misconceptions and given me a lot to think about as I manage my own weight.

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