June 6, 2022 – “You want fries with that?”
The way you solution that query can have much less to do with strength of will than chances are you’ll suppose.
Virginia Tech scientists are taking a deep dive into the mind chemistry that drives cravings for bad fatty meals. Their objective: To determine if the country’s ever-expanding waistline has as a lot to do with that’s in our heads as what we put into our bellies.
Armed with a brand new $2 million grant from the Nationwide Institutes of Well being, the researchers have introduced a brand new learn about to know the mind circuitry that can be a key driving force of the country’s weight problems disaster. In particular, the scientists are having a look on the wiring in our brains that makes us consume an excessive amount of high-fat meals after a length of fending off them.
Lead researcher Sora Shin, PhD, says she hopes the paintings will provide an explanation for a key explanation why such a lot of dieters fail. The findings may explain why reducing your favourite tasty treats from your vitamin can in reality make you crave them much more – and level how one can doable new approaches to struggle overeating.
“Excessive consumption of palatable foods … such as cake, potato chips, and ice cream is a major public health problem leading to obesity,” says Shin, an assistant professor on the Fralin Biomedical Analysis Institute at Virginia Tech. “Although numerous appetite control strategies are developed for the treatment of obesity, most of the individuals who achieved a successful diet show high rates of relapse to HFD [high-fat diet] overconsumption.”
“Understanding neural [brain] circuit mechanisms leading to HFD overconsumption after abstinence is arguably the core issue in developing therapeutic strategies for the long-term treatment of obesity,” she says.
Shin and her colleagues hope to construct on many years of study – together with her personal previous research involving mice – appearing that positive hormones, similar to leptin, have a profound affect on urge for food and overeating. The Virginia Tech learn about will center of attention at the “leptin-response circuit” within the mind “in hopes of speeding the development of novel therapeutic strategies for the treatment of maladaptive eating disorders and obesity,” she says.
In the end, mavens say Shin’s analysis may result in game-changing medicines to assist combat the weight problems disaster. However within the brief time period, well being experts say the paintings may most probably sprint the concept overweight persons are only guilty for his or her weight issues.
“I think studies like this are necessary because [when] we see an obese person, you just probably blame the person for not taking enough action to combat obesity,” notes Dipali Sharma, PhD, a professor of oncology at Johns Hopkins College Faculty of Drugs and a professional in weight problems and most cancers.
“But we have seen in our own trials that some people actually have a propensity to gain weight [even] when they are following up with the exercise routines and food regimens that are recommended to everyone. So, we should be appreciative of the facts – that this is not just willpower and stop the blame game – and then clinically we can look at other approaches.”
Leptin: The Key to Obesity?
According to the World Health Organization, more than a billion people worldwide are obese, which increases the risk for heart disease, stroke, diabetes, certain cancers, and other leading causes of preventable death.
In the U.S. alone, more than four in 10 adults are clinically obese, according to the CDC. And those numbers are rising – up 30.5% over the past 2 decades, the agency estimates.
A primary culprit? Access to so many low-cost, high-calorie, fat-rich treats that our brains are prewired to crave, experts say. But another key factor has been the subject of a great deal of scientific research: leptin, the “hunger hormone.”
Leptin is one of several hormones made by fat cells that can lessen your appetite by signaling to your brain that you are “full” after eating and that your body has enough energy stores (such as body fat). Some is also produced by your stomach when you eat; it circulates in your blood and travels to your brain.
Leptin helps maintain a healthy body weight over long periods of time through its interaction with your brainstem and hypothalamus, the region of the brain responsible for self-regulating processes, such as body temperature, thirst, and hunger.
Leptin also appears to affect metabolism, endocrine system regulation, the immune system, and cancer growth, Sharma notes
In general, blood levels of the hormone are lower in thin people and higher those who are overweight or obese, studies show. But leptin levels can vary depending on many things, including when you last ate and your sleep patterns.
Leptin has a more profound effect when you lose weight. As you lose body fat, your leptin levels decrease, which signals your brain to think that you are starving. This stimulates intense hunger and appetite and can lead to overeating.
Avoiding high-fat foods can help ease your appetite and cravings by affecting leptin levels. But eating fatty foods can increase caloric intake, weight gain, and fat storage – all of which contribute to obesity.
What’s more, many obese people don’t respond well to leptin’s appetite-suppressing signals even though they have higher levels of leptin, Sharma explains. Some research shows obesity can lead to a kind of resistance to the appetite-suppressing effects of leptin, which makes it harder for people who have obesity to resist cravings for fatty foods.
If you have leptin resistance, your brain doesn’t respond as well as it should to leptin, so you don’t get the sensation of feeling full, and you eat more, even though your body has enough fat stored. Leptin resistance also causes your body to enter starvation mode, so your brain decreases your energy levels and makes you use fewer calories to preserve fat reserves.
For years, researchers have been working to develop therapeutics that can control hunger hormones like leptin to fight obesity and leptin resistance. Early results of that research have been promising:
- Mayo Clinic scientists have found that injecting a hunger-blocking hormone into mice stopped the typical weight gain after dieting and helped prevent rebound obesity. “We think this approach – combined reduction of calories and hormone ─ may be a highly successful strategy for long-term weight control,” says W. Stephen Brimijoin, PhD, a Mayo Clinic pharmacologist and co-author of the study, published in the Proceedings of the National Academy of Sciences. “Given the growing obesity crisis worldwide, we are working hard to validate our findings for medical intervention.”
- Heike Muenzberg-Gruening, PhD, director of the Central Leptin Signaling Laboratory at Pennington Biomedical Research Center in Louisiana, has just launched one of seven new National Institutes of Health-backed studies to find out how the brain and fat tissue “communicate” to control the release of leptin and other hormones. “Fat tissue plays an important role in our health,” she notes, saying the research could lead to new therapies. “It stores and breaks down fat but also secretes hormones like leptin to impact energy expenditure, food intake, and blood sugar levels.”
- And Baylor College of Medicine scientists have found that leptin may be only one part of the gut-brain connection to obesity. In a study published in the Journal of Clinical Investigation, researchers found high-fat diets increase production of a gut hormone (known as GIP) that blocks leptin’s effects – possibly explaining leptin resistance. “We have uncovered a new piece of the complex puzzle of how the body manages energy balance and affects weight,” says study co-author Makoto Fukuda, PhD, an assistant professor at Baylor. “We didn’t know how a high-fat diet or overeating leads to leptin resistance. My colleagues and I started looking for what causes leptin resistance in the brain when we eat fatty foods, [and] we discovered a connection between the gut hormone GIP and leptin.”
Decoding the Gut-Brain Connection
Scientists who have been studying leptin since its discovery in 1994 aren’t entirely certain just how and why this complex interaction of fat, hormones, and brain circuitry drive obesity.
“When leptin was discovered, everybody thought that we found the magic bullet for obesity,” Sharma says. “But it’s more complicated than that. We know now, it’s not that simple that leptin is acting alone – that’s not the case. Leptin does induce a lot of circuits in our cells and in a lot of pathways that trigger a lot of responses … not only in the brain, but also in various kinds of cells, including cancer cells.”
That’s where Shin and her team of researchers come in – to understand the complex but elusive gut-brain circuits that leptin impacts.
The Virginia Tech team is targeting this gap in scientific knowledge to identify the brain pathways responsible for high-fat diet relapse.
In lab research, Shin and her colleagues discovered that mice exposed to a high-fat diet tended to select high-fat foods when given the choice over their normal diet. But they also found the rodents ate too much after a period of not having fatty foods.
And not only mice tend to do that, she says. Anyone who’s ever been on a diet that restricts fat knows that you may lose weight at first but feel powerful cravings for such foods. Eventually, most dieters relapse – returning to their former high-fat eating habits, just like Shin’s mice, and overeating.
What drives that pattern, she says, has less to do with willpower than with the brain’s response to leptin.
“Our study is significant, because for the first time, we will have an important framework for clarifying how the leptin-responsive brain circuit responds to high-fat food exposure, and how that interaction increases the risk of emotional overeating following a period of abstinence,” says Shin, an assistant professor in the Department of Human Nutrition, Foods and Exercise in the College of Agriculture and Life Sciences at Virginia Tech.
Her learn about is the primary of its type to seem extra carefully on the quite a lot of mind areas believed to play a central position in regulating meals consumption and frame weight, advancing what is understood about obesity-related hormones.
“It should lead to a conceptual advance in how we think about the central leptin’s action and its sensitivity from the cellular level, one brain site, to a more holistic, distributed network level,” she says. “In the practical point of view, we can also expect that successful completion of this study will provide important insights for developing precise brain circuit-based targets which will guide translational work to create new circuit therapeutics for treating pathological binge-eating habits or relapse to obesity.”
The large image: Shin says the proof displays that weight problems is, no less than partially, a results of a “problem of brain circuit dysfunction in molecular and neuronal level, instead of [an] individual willpower issue.”
So, what’s the sensible take-home message of the rising science on leptin, weight problems hormones, and weight acquire?
Whilst long run remedies might assist goal excessive leptin ranges or leptin resistance, Sharma and different mavens say the most efficient factor you’ll be able to do lately is practice the tried-and-true recommendation on keeping up a wholesome frame weight.
- Devour nutrition-rich, balanced foods and restrict high-fat meals and snacks.
- Get common workout – intention for approximately half-hour maximum days of the week.
- Organize rigidity ranges and intention to get no less than 7 hours of sleep every night time. (Deficient sound asleep conduct and excessive ranges of rigidity are each related with weight acquire.)
There’s some other giant take-away from the rising science on leptin and weight problems, Sharma says.
“I think definitely, this kind of research will actually uncover a lot of new circuits, so maybe in the future, we can have some new tools to help these people,” she says. “But from the get-go at least, this research will lead to more understanding, in the sense of why do people fall off their diet plans, because that is a very big problem, and how we should not be just blaming them for having no willpower.”
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