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We sit down with Franchell Hamilton, a bariatric surgeon, to explore the intriguing link between genetics, brain function, and obesity. She shares her insights into why many patients don’t feel full even after eating, even post-bariatric surgery. We delve into the role of dopamine signaling in the brain, genetic factors like the DRD4 gene, and how they influence eating behavior and body weight. Join us for a deep dive into the complex science behind overeating and the potential game-changing impact of once-a-week GLP-1 medications.

Franchell Hamilton is a bariatric surgeon.

She discusses the KevinMD article, “Uncovering the truth about genetic mutations and weight loss.”

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Transcript

Kevin Pho: All right, welcome to the show. Subscribe at KevinMD.com/podcast and get CME for this episode by clicking on the CME link in the show notes. Today we welcome Franchell Hamilton. She’s a bariatric surgeon. Her KevinMD article is titled “Uncovering the truth about genetic mutations and weight loss.” Franchell, welcome to the show.

Franchell Hamilton: Thank you. Thank you so much for having me.

Kevin Pho: So let’s start by sharing your story and journey to where you are today.

Franchell Hamilton: I love obesity medicine, and I took a roundabout way, so to speak, to get there. I feel like I’ve always been someone who roots for the underdog, so to speak, and I’m very passionate about people who I feel are underrepresented, and there’s a lot of work to do in this area. I started off doing regular general surgery, back in the early 2000s, when we only did obesity surgery for the people who, quote unquote, really needed bariatric surgery. I requested to shadow some of the bariatric surgeons who were doing these surgeries at the time, and I would sit and really listen to these patients. They would talk about how they’d tried everything and done everything. Then the surgeon would say, “Well, this surgery can lead to death,” and put all these things on the table, and patients would say, “I’m willing to try anything at this point. I don’t care. I’m tired of dealing with this.”

When I actually listened to these patients’ stories, I knew there was more to obesity medicine, or even more to bariatric surgery, than just the operation. These people truly struggled, and I almost look at it as a mental health disease as well. It just was not as well known then, because we were very much “calories in, calories out.” That’s what made me go into bariatric surgery and start figuring out what is going on here. There’s more to it than just giving these people bariatric surgery. People were volunteering, knowing they might die on the table, to get rid of this disease. So I’m glad the AMA finally recognized it as a disease, and all the stuff moving forward. That’s kind of what got me to where I am today. I always knew there was something more to this, and that’s where all of my decades of research in this area have come from.

Kevin Pho: All right, so let’s talk more about your KevinMD article, where you discuss some of those issues in depth. It’s titled “Uncovering the truth about genetic mutations and weight loss.” So how did your article come together?

Franchell Hamilton: The biggest portion of what I study now is genetics, and I also look at a lot of brain science, because I feel those two go together when it comes to treating obesity. It started with my doing these bariatric surgeries, and then, like a lot of people are seeing, patients would regain. But I didn’t feel it was just regain because, “Oh, they couldn’t stop eating,” X, Y and Z. I always felt there was something that would trigger this, something behind the scenes. So I started doing a lot more research into genes and into the brain, and into how all these different mutations and genes affect signaling to the brain, where people literally cannot sense that they’re full. It’s not something they want to have, or something where they just lose control over it; it’s literally a genetic mutation that’s causing that. That opened up the door to identifying so many other genetic mutations that can cause different types of obesity, with different presentations: over 900 genes so far that contribute to obesity.

Kevin Pho: So talk more about that genetic component of obesity. How is it passed down from generation to generation? Do we have a lot of research in terms of who would be more susceptible to these mutations?

Franchell Hamilton: It definitely can be passed down; some of the genes can be passed on. We all actually have this thrifty gene that a lot of people have talked about before. I have it. This gene was around a long time ago, when we were hunters and gatherers, and it allowed us to hold on to weight. We would eat, and because our body knew it might not see food for a day, or who knows how long back in those days, it had us store. So it was a storage gene, and it would release signals that caused our body to act appropriately. A lot of us today actually still have that gene, which is why starvation diets don’t work long term. Whenever we go longer periods of time, when you try to significantly decrease your calories or go a long time without eating, this gene kind of clicks in and does what it’s supposed to do: “Let me hold on and store everything I have, because we don’t have the energy to be burning.” So that’s one of the genes most of us actually have, and if we eat and do things the right way, that gene will never really click on. Then there are other genes that lie dormant, that may have been passed on to people, but then get turned on by environmental factors.

Kevin Pho: So if you discover that someone has a genetic predisposition to obesity, how does that affect your management and treatment?

Franchell Hamilton: A lot of it depends on the gene. I personally break these genes into two categories: central-acting, which is a lot of brain stuff, how we perceive signals, and peripheral-acting, meaning how our body responds, how our fat tissue responds and how our muscle responds. A lot of the central-acting ones are being researched now. MC4R and leptin receptor genes, as far as obesity goes, now have targeted medications. Some people have central-acting genes that cause what we call hyperphagia, where people overeat and almost can’t control themselves. Believe it or not, bariatric surgery helps only slightly; it does minimal. I was doing these surgeries on people who have these hyperphagia-type genes, and afterward they were almost eating, what I would call, through the surgery. I thought, “How are you doing this? I know how big I made that stomach. How is it possible for them to do that?” And come to find out, it’s a central-acting mutation. They don’t have the switch that cuts off satiety and says, “I’m full.” So giving them bariatric surgery may only get them so far. That’s how it’s helped me manage my practice: who is a good candidate for bariatric surgery, and, for people who have these genes, certain more targeted medications may be a little better, along with surgery or instead of surgery.

Kevin Pho: Now, are these tests widely available? Is this something obesity medicine specialists routinely order for their patients? How easy is it to order these tests?

Franchell Hamilton: Good question, and that’s the thing. The answer is that they are available, but no, they are not routinely tested. I test them, because this is obviously an area I wanted to dive into and learn more about, but most obesity specialists do not test them, and most bariatric surgeons do not test them. We always do the basic blood work, but my goal is to bring awareness that this needs to be an integral part of a workup for obesity, especially in people who have pediatric or adolescent obesity. I do a lot of that, and that’s where a lot of this stemmed from. When you are five or six and you start developing obesity at this young age, it can’t just be, “Oh, the parents aren’t giving them the right nutrition.” Obviously all that plays a role, but believe it or not, we’re finding more and more that the younger population has these genetic mutations, and then they go into adulthood also not understanding why they’re obese, and it’s because of a lot of these genetic mutations.

There are different companies that do them. One of the ones that does most of the obesity-related testing is Rhythm Pharmaceuticals, at uncoveringrareobesity.com. That company will do it for free for a lot of patients. With other ones, the patient will have to pay, because unfortunately this is not covered by insurance.

Kevin Pho: So tell us some of the obstacles and barriers preventing these tests from becoming more mainstream and routinely ordered by physicians today.

Franchell Hamilton: Well, I think part of it is just the lack of awareness. Even when I came through, we would say rare obesity-related genetic disorders are rare, almost like some of the trisomies that can happen in the womb. We just kind of chalked it up as a community: “Oh, genetic disorders for obesity are rare.” We didn’t even want to test for them. Then, come to find out, there are actually so many genes that can lead to obesity, that cause obesity if there are mutations. So I think that was one of the obstacles, just not having enough awareness that this is a cause of a lot of obesity disorders.

Then there’s getting access to it. If something is not covered by insurance, it’s going to be very difficult for a patient to want to pay out of pocket when they’re already paying all this money monthly for insurance. We have the same fights in bariatric surgery. So that’s another barrier for a lot of physicians: They can’t get insurance to cover it, and they don’t know where to go to order it. So it’s threefold. We don’t think of it as an option during our normal workup, insurance is not covering it, and we don’t even know where or how to order it, if it’s something we’re even thinking about doing.

Kevin Pho: Now, if physicians were interested in looking more for these genetic predispositions to obesity, share some resources where physicians can learn and find out more.

Franchell Hamilton: One of the places you can go is 3X4 Genetics; you just need to look it up. 3X4 Genetics does reasonable and affordable genetic testing, and the good thing about that one is that it covers not just obesity but cardiovascular health, diabetes, all the things that go along with obesity. I’ve even tested myself, and it’s very interesting, and we can use these as tools for prevention. So that’s one of the resources I like to use. The other one is uncoveringrareobesity.com, literally like that. That one doesn’t do the additional cardiovascular and diabetic health testing, but it does focus specifically on 70 to 80 genes for obesity mutations, and that can often be done for free.

Kevin Pho: So how about in the primary care setting? Let’s say one of my patients comes to me, I order one of these tests, and we find out they have some type of genetic predisposition to obesity. As a primary care doctor, what should I do next? What would be my next steps in terms of their management?

Franchell Hamilton: The next step: A lot of these places that do the genetic testing have free genetic counseling for patients. Even for some of the results I don’t understand, uncoveringrareobesity.com says on the printout that gives you the information, “If your patient wants to talk to a genetic counselor, feel free to set up a free consultation.” So that would be my next step. If any of these things come up, I would recommend that they talk to a genetic counselor. 3X4 Genetics offers free training weekly to help physicians navigate how to read and understand these genetic tests, and a lot of the genetic tests will go line by line explaining what the results mean and offer treatments. That’s the other thing, especially with 3X4 Genetics. They will say, “This person is predisposed to diabetes. This particular diet will be best for them. If they get it, this particular medication.” So they literally outline it, and physicians can always reach out to the company if they have additional questions.

Kevin Pho: So I want to shift gears and get your perspective on the current state of bariatric surgery. As you know, there are GLP-1 medications like Ozempic and Wegovy, and certainly in primary care I manage a lot of these medications. How has the prominence of these medications affected bariatric surgery?

Franchell Hamilton: Well, I will say, Kevin, I’m probably doing more obesity medicine than surgery. There are these medications, and there are even more on the horizon. I’m really big on weight regain, and I do a lot of medical management of my bariatric patients who regain, and even preoperatively. So I’m all for combination therapy, even as a bariatric surgeon, because I’ve seen the effectiveness of these meds. I’ve had patients come back after surgery who are now on these GLP-1s, and they say that for some aspects of their weight loss journey, the medication worked better.

So it’s just very interesting to see. For example, the sleeve does a really good job with appetite. It changes your ghrelin and leptin hormones; we’ve documented this, and it helps really well with that. But for people who have more of an addictive personality toward food, it’s not as effective. Believe it or not, because these particular medications, in general, block the reward center in the brain, which surgery does not do, some of them can actually be more effective, depending on the cause or the genetic mutations of the person’s obesity. So I think these new medications, and there are 70 more coming out, by the way, mimicking these GLP-1s in some form or fashion, are going to really change bariatric surgery. And to be honest, I’m excited to see what’s going to happen.

Kevin Pho: We’re talking to Franchell Hamilton. She’s a bariatric surgeon. Today’s KevinMD article is titled “Uncovering the truth about genetic mutations and weight loss.” Franchell, tell us some of the take-home messages that you want to leave with the KevinMD audience.

Franchell Hamilton: Well, thank you so much. When people are seeing patients for obesity, I almost want to get rid of the whole mindset of “calories in, calories out.” There are so many other factors that play a role in obesity. If you’re a PCP, or you’re in medicine, or even a surgeon, and you’re treating people with obesity and your approach is not as effective as you feel it could be, don’t automatically assume the patient is not doing something they should be doing. Start thinking outside of the box, and start thinking about genetics at that point. If you don’t feel like you want to do it at the first visit or the first workup, I understand. You want to try nutrition, behavioral modifications, medications and/or surgery, if you’re a surgeon. Then, in the event the patient is still struggling, I think having the additional knowledge of the genes is going to be very helpful, not only for you as the practitioner, to understand what’s going on or why these meds aren’t working, but also for the patient, so they don’t blame themselves and carry this weight stigma that our society puts on them. Understanding “I have a genetic mutation, and this is the reason I’m struggling with obesity; it’s not me,” I think, is also very important for the patients.

Kevin Pho: Franchell, thank you so much for sharing your perspective, time, and insight, and thanks again for coming on the show.

Franchell Hamilton: I love talking about this.