Of course you know that eating is vital to your survival, but have you ever thought about how your brain controls how much you eat, when you eat and what you eat?
This is not a trivial question, because two-thirds of Americans are either overweight or obese and overeating is a major cause of this epidemic. To date, the scientific effort to understand how the brain controls eating has focused primarily on brain areas involved in hunger, fullness and pleasure. To be better armed in the fight against obesity, neuroscientists, including me, are starting to expand our investigation to other parts of the brain associated with different functions. My lab’s recent research focuses on one that’s been relatively overlooked: memory.
For many people, decisions about whether to eat now, what to eat and how much to eat are often influenced by memories of what they ate recently. For instance, in addition to my scale and tight clothes, my memory of overeating pizza yesterday played a pivotal role in my decision to eat salad for lunch today.
Memories of recently eaten foods can serve as a powerful mechanism for controlling eating behavior because they provide you with a record of your recent intake that likely outlasts most of the hormonal and brain signals generated by your meal. But surprisingly, the brain regions that allow memory to control future eating behavior are largely unknown.
Memories of last meal influence the next
Studies done in people support the idea that meal-related memory can control future eating behavior.
When researchers impair the memory of a meal by distracting healthy participants while they eat – such as by having them play computer games or watch television – people eat more at the next opportunity. The opposite is also true: enhancing meal-related memory by having people reflect on what they just ate decreases future intake.
Patients suffering from amnesia do not remember eating and will eat when presented with food, even if they have just eaten and should feel full. And memory deficits are associated with overeating and increased weight in relatively healthy people.
So what’s going on? We all know that we don’t eat just because we’re hungry. Most of our decisions about eating are influenced by a myriad of other influences that have nothing to do with how hungry or full we are, such as time of day, the sight and smell of food, or an advertisement for a favorite restaurant. My lab has chosen to focus on memory, in part, because it is something that is adaptable and more within our control.
We’ve started our search by focusing on a brain region called the hippocampus, which is absolutely vital for personal memories of what, where and when something happened to you.
Interestingly, hippocampal cells receive signals about hunger status and are connected to other brain areas that are important for starting and stopping eating, such as the hypothalamus. My colleagues and I reasoned that if hippocampal-dependent memory inhibits future eating, then disrupting hippocampal function after a meal is eaten, when the memory of the meal is being stabilized, should promote eating later on when these cells are functioning normally.
Effect of turning neurons off, then back on
In my lab, we tested this prediction using optogenetics. This state-of-the-art method uses light to control individual cells in a behaving animal. We were able to inhibit hippocampal cells for 10 minutes before, during or after rats ate a meal.
To do this, we inserted a specific gene into hippocampal cells that caused these cells to immediately stop functioning as soon as we shined light of a certain wavelength on them. The cells remained inactive as long as we shined the light. Crucially, their function returned to normal as soon as we turned the light off.
We discovered that optogenetically inhibiting hippocampal cells after rats ate a meal caused the animals to eat their next meal sooner and caused them to eat almost twice as much food during that next meal. And remember, the hippocampal cells were working normally by the time the rats ate again. We saw this effect after the intervention whether the rats were offered rodent chow, a sugar solution, or water sweetened with saccharin.
That rats would eat more saccharin after we interfered with their hippocampal function is particularly interesting because saccharin is a noncaloric sweetener that produces very few of the gastrointestinal (GI) chemical signals normally generated by food. We concluded that the effect we saw after inactivating hippocampal cells is most likely explained by an effect on memory consolidation, rather than by an impaired ability to process GI messages.
Thus, our findings show that hippocampal cells are necessary during the period following a meal for limiting future energy intake. We suggest that neurons in the hippocampus inhibit future eating behavior by consolidating the memory of the preceding meal.
These findings have significant implications for understanding the causes of obesity and the ways in which to treat it. Scientists, including my research group have shown in previous studies that feeding rats too much fat or sugar impairs hippocampal memory. Similarly, overeating and obesity in humans are associated with hippocampal damage and hippocampal-dependent memory deficits.
Impaired hippocampal functioning, in turn, leads to further overeating and weight gain, leading to a vicious cycle that may perpetuate obesity. Our research adds to the growing body of evidence that suggests that techniques that promote hippocampal-dependent memories of what, when and how much one eats may prove to be promising strategies for reducing eating and promoting weight loss.
Author: Marise Parent, Professor of Neuroscience and Psychology and Associate Director of the Neuroscience Institute, Georgia State University. Parent receives funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH). Georgia State University provides funding as a founding partner of The Conversation US.
kyren mannix, logged in via Google: Your tests seem to imply that you can impair hippocampal functioning simply by distraction. How can this be? We know stress affects the hippocampus, and hinders the normal ways of learning from past experience, but you seem to ignore that side of it. Yet it would seem a profitable area to explore. Perhaps eating itself is stressful for some people. It is for me. I know I was force fed in hospital as a small child and maybe, like PTSD, the memories are encoded into our system.
Marise Parent, In reply to kyren mannix: Thanks for your comments. We did not use distraction in our tests, but distraction does impair memory in that the information does not make it into the brain via attention and therefore cannot be remembered. We agree that stress is a very important variable and it is one that we would like to include in our future studies.
The Prohibition-era origins of the modern craft cocktail movement
January 15, 2019
By the end of Prohibition, distilled spirits made up more than 75 percent of alcohol sales.
Author: Jeffrey Miller, Associate Professor and Program Coordinator, Hospitality Management, Colorado State University
Disclosure statement: Jeffrey Miller does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.
Partners: Colorado State University provides funding as a member of The Conversation US.
With America in the middle of a flourishing craft beer and craft spirits movement, it’s easy to forget that Prohibition was once the law of the land.
One hundred years ago, on Jan. 16, 1919, Nebraska became the 36th of the country’s 48 states to ratify the 18th Amendment, reaching the required three-fourths threshold.
The law forbid the production of beverages that contained more than one-half of 1 percent alcohol. Breweries, wineries and distilleries across America were shuttered. Most never reopened.
Prohibition may be long dead, but the speakeasies and cocktails it spawned are still with us. Much of the era’s bootleg liquor was stomach-turning. The need to make this bad alcohol drinkable – and to provide buyers a discreet place to consume it – created a phenomenon that lives on in today’s craft cocktail movement and faux speakeasies.
For better or worse, Prohibition changed the way Americans drank, and its cultural impact has never really gone away.
Bootleggers get creative
During Prohibition, the primary source of drinking alcohol was industrial alcohol – the kind used for making ink, perfumes and camp stove fuel. About 3 gallons of faux gin or whiskey could be made from 1 gallon of industrial alcohol.
The authors of the Volstead Act, the law enacted to carry out the 18th Amendment, had anticipated this: It required that industrial alcohol be denatured, which means that it’s been adulterated with chemicals that make it unfit to drink.
Bootleggers quickly adapted and figured out ways to remove or neutralize these adulterants. The process changed the flavor of the finished product – and not for the better. Poor quality notwithstanding, around one-third of the 150 million gallons of industrial alcohol produced in 1925 was thought to have been diverted to the illegal alcohol trade.
The next most common source of alcohol in Prohibition was alcohol cooked up in illegal stills, producing what came to be called moonshine. By the end of Prohibition, the Prohibition Bureau was seizing nearly a quarter-million illegal stills each year.
The homemade alcohol of this era was harsh. It was almost never barrel-aged and most moonshiners would try to mimic flavors by mixing in some suspect ingredients. They found they could simulate bourbon by adding dead rats or rotten meat to the moonshine and letting it sit for a few days. They made gin by adding juniper oil to raw alcohol, while they mixed in creosote, an antiseptic made from wood tar, to recreate scotch’s smokey flavor.
With few alternatives, these dubious versions of familiar spirits were nonetheless in high demand.
Bootleggers much preferred to trade in spirits than in beer or wine because a bottle of bootleg gin or whiskey could fetch a far higher price than a bottle of beer or wine.
Prior to Prohibition, distilled spirits accounted for less than 40 percent of the alcohol consumed in America. By the end of the “noble experiment” distilled spirits made up more than 75 percent of alcohol sales.
Masking the foul flavors
To make the hard liquor palatable, drinkers and bartenders mixed in various ingredients that were flavored and often sweet.
Gin was one of the most popular beverages of the era because it was usually the simplest, cheapest and fastest beverage to produce: Take some alcohol, thin it with water, add glycerin and juniper oil, and voila – gin!
For this reason, many of the cocktails created during Prohibition used gin. Popular creations of the era included the Bee’s Knees, a gin-based drink that used honey to fend off funky flavors, and the Last Word, which mixed gin with Chartreuse and maraschino cherry liqueur and is said to have been created at the Detroit Athletic Club in 1922.
Rum was another popular Prohibition tipple, with huge amounts smuggled into the country from Caribbean nations via small boats captained by “rum-runners.” The Mary Pickford was a cocktail invented in the 1920s that used rum and red grapefruit juice.
The cocktail trend became an important part of home entertaining as well. With beer and wine less available, people hosted dinner parties featuring creative cocktails. Some even dispensed with the dinner part altogether, hosting newly fashionable cocktail parties.
Cocktails became synonymous with America the way wine was synonymous with France and Italy.
A modern movement is born
Beginning in the late 1980s, enterprising bartenders and restaurateurs sought to recreate the atmosphere of the Prohibition-era speakeasy, with creative cocktails served in dimly lit lounges.
The modern craft cocktail movement in America probably dates to the reopening of the legendary Rainbow Room at New York’s Rockefeller Center in 1988. The new bartender, Dale Degroff, created a cocktail list filled with classics from the Prohibition era, along with new recipes based on timeless ingredients and techniques.
Around the same time, across town at the Odeon, bar owner Toby Cecchini created “Sex and the City” favorite the Cosmopolitan – a vodka martini with cranberry juice, lime juice and triple sec.
A movement was born: Bartenders became superstars and cocktail menus expanded with new drinks featuring exotic ingredients, like the Lost in Translation – a take on the Manhattan using Japanese whiskey, craft vermouth and mushroom-flavored sugar syrup – or the Dry Dock, a gin fizz made with cardamom bitters, lavender-scented simple syrup and grapefruit.
In 1999, legendary bartender Sasha Petraske opened Milk & Honey as an alternative to noisy bars with poorly made cocktails. Petraske wanted a quiet bar with world-class drinks, where, according to the code for patrons, there would be “no hooting, hollering, shouting, or other loud behavior,” “gentlemen will not introduce themselves to ladies” and “gentlemen will remove their hats.”
Petraske insisted on the highest quality liquors and mixers. Even the ice was customized for each cocktail. Many of what are now clichés in the craft cocktail bars – big, hard ice cubes, bartenders with Edwardian facial hair and neckties, rules for entry and service – originated at Milk & Honey.
A lot of the early bars that subscribed to the craft cocktail ethos emulated the speakeasies of the Prohibition era. The idea was to make them seem special and exclusive, and some of the new “speakeasies” incorporated gimmicks like requiring customers to enter behind bookcases or through phone booths. They’re meant to be places where customers can come to appreciate the drink – not the band, not the food, not the pickup scene.
Luckily, today’s drinker doesn’t have to worry about rotgut liquor: The craft distilling industry provides tasty spirits that can be either enjoyed in cocktails or simply sipped neat.
How to train the body’s own cells to combat antibiotic resistance
January 15, 2019
Postdoctoral Fellow, University of Pennsylvania
Zahidul Alam does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.
Drug-resistant superbugs have threatened human health for decades. The situation is getting worse because of the shortage of new antibiotics. But what if we changed the way we aim to treat them, and trained our cells to kill these invaders instead of relying on antibiotics to do the dirty work? This new strategy, called host-targeted defense, could help to solve antibiotic resistance problem.
Antibiotic resistance is a growing concern for global health. A recent report commissioned by the British government shows that every year globally around 700,000 people died due to infections caused by drug-resistant bacteria. The report also warned that, without action, the death toll could rise to 10 million globally and cost US $80 trillion to the global economy.
Drug resistance is a serious problem in the United States too. More than 23,000 people die every year due to multidrug-resistant pathogens and cost the country around $55 billion per year. The main culprits threatening the U.S. are methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE) and Clostridium difficile.
The shortage of new antibacterial drugs in development to tackle the growing threat is a disturbing trend. A pathogen that is resistant to a drug reserved to treat infections when all others have failed is a particular concern. This is the case with carbapenem-resistant pathogen.
The decline in antibacterial drugs coupled with emergence of drug-resistant pathogens demands alternative approaches.
In Malay Haldar’s lab, along with other projects, my colleagues and I are studying how factors in an animal host play a role in response to infections. To test the approach, we are doing this work using a mouse model of infections. Our aim is to find novel traits or factors of the host that can be targeted to boost an individual’s immune response high enough to kill the offending microbes. The host factor we are investigating is called Spi-C, a gene found in every cell of the human body.
Targeting host factors
My interest in host factors arose during my graduate studies. While working on my Ph.D. research project, I learned that host factors, a variety of traits intrinsic to humans, play a significant role in bacterial infections. This inspired me to investigate how the host’s immune system fights bacteria.
New insights into the host’s defense against pathogens have led researchers to explore a new strategy called host-directed therapy (HDT), a relatively recent idea that has only been around for about a decade.
The goal of HDT is to enhance and amplify the host’s immune response to kill pathogens, rather than relying exclusively on antibacterial drugs. By targeting host factors as well as delivering antibiotic treatment, HDTs deliver a double whammy.
The body naturally responds to infections with inflammation, a process in which specific populations of immune cells attack and kill the invading bacteria by either eating them or zapping them with protein weapons. However, uncontrolled inflammation triggers the production of proteins that can cause multi-organ failure and can even kill the host. Therefore, controlling inflammation is crucial to combat pathogens as well as to protect the body from hyperinflammation.
HDTs include a suite of treatments that boost the host response to pathogens and also protect the host from exaggerated immune response. HDTs include cellular therapy, in which a specific population of bone marrow cells are injected into the host body to prevent excessive immune response and tissue injury. Another HDT involves commonly used drugs for noninfectious diseases. Statins and ibuprofen, for example, calm the host response to infections. Biologics, the complex molecule drugs produced by recombinant DNA technology, do this too by neutralizing small-sized proteins and reducing tissue damage. Nutritional products, such as vitamin D3, have also been shown to cause a host’s immune cells to release antibacterial substances that enhance pathogen killing.
HDTs in conjunction to antibacterial drugs show great promise in treating various multidrug-resistant pathogens, notably against Mycobacterium tuberculosis, the pathogen which causes tuberculosis, one of the top 10 causes of death worldwide.
Personalizing treatments for infections
In the last decade, researchers have made much progress in host factor research, leading to new therapeutic strategies.
One of them is personalized medicine, in which a genomic blueprint can determine an individual’s unique susceptibilities to diseases and choose appropriate therapies.
This concept is applied in noninfectious diseases like cancer. However, the application of the concept in infectious disease is very recent. Nonetheless, personalized medicine leads us to speculate why some individuals are more prone to infections than others. My colleagues and I believe that such differences may be caused by subtle differences in the DNA of the host factor genes. By connecting these differences, called polymorphisms, to the level of individuals’ vulnerability to infections, we hope that our research will contribute to the precision medicine of bacterial infections.
Our quest for a novel host factor
My colleagues in the Haldar lab and I are exploring the role of Spi-C in bacterial infection. Spi-C is essential for the development of a specific type of population of cells in the spleen that regulate the iron storage in the body. Iron is essential for transporting oxygen in red blood cells.
But, during infections, bacteria also require iron. They need it for growth, and they compete with the host to get it. Hence, if we could alter the activity of the Spi-C gene, we might be able to deprive bacteria of this vital nutrient and thus stop the infections without harming the host.
In a recent paper, we summarized the effect of iron in host cells and its interactions with host factors in the presence or absence of infections.
In mice, we tested the role of host factor, Spi-C, as a way to defend the host. In this study we injected a chemical that is a component of the bacteria into the mice. We wanted to trigger changes that occur in the animal during a real bacterial infection.
Our preliminary results showed that the host factor is active in various organs of the mice treated with the chemical. We believe this activation plays a role in host-defense. And, indeed, we found that losing Spi-C activity increased the release of small-sized proteins that facilitate the host defense against pathogens compared to the cells that have normal Spi-C activity. We believe this change in small-sized proteins might protect the host from hyperinflammation in response to infection.
We believe that shifting of our thinking from pathogen-targeted therapy to host-directed therapy ushers in a new avenue of precision medicine, which could help to end the drug resistance crisis.