Happy genes love to eat

 Special people with special genes are always happy and love to eat. We are also influence by our environment but our genes is our master control until we harmed our genes from forces in the environment, prenatal nutrition , stress and other factors.

Connie

Opioid receptor was present in the nerves associated with the portal vein that collects blood from the gut

  • Opioid Receptor Satiety Signal | Science Signaling

    The sensations of hunger and satiety are mediated through communication between the gastrointestinal system and the brain. Duraffourd et al. found that μ-opioid receptor (MOR)–1 was present in the nerves associated with the portal vein that collects blood from the gut. Peptide products of protein digestion can function …

    • stke.sciencemag.org/content/5/234/ec195

    DOI: 10.1126/scisignal.2003416

  • Synthesizing the Opioid Peptides

    Synthesizing the Opioid Peptides. The opioid peptides are synthesized as parts of large precursor molecules that may be split to yield different products in different cells. The biosynthesis of the opioid pep- tides illustrates what seemsto be a gen- eral trend in neurobiology. Likemany other peptides that act in the nervous.

    • science.sciencemag.org/content/sci/220/4595/395.full.pdf
  • SCIENCEINSIDER

    Drug, HIV crises hit HHS nominee Price close to home | Science …

    Dec 2, 2016  But Price’s district is also experiencing some public health crises that he will likely be dealing with as HHS secretary: a serious heroin and opioid abuse epidemic, as well as elevated HIV infection rates. The heroin problem was described in great detail in this investigative special by the local NBC affiliate …

  • REPORT

    COMT val158met Genotype Affects µ-Opioid Neurotransmitter …

    We detected significant effects of genotype on μ-opioid system activation (degrees of freedom = 2, 15 for all regions,P < 0.05 after correction for multiple comparisons) in the anterior thalamus [x, y, zcoordinates (millimeters), 5, −1, −2; F = 29.3], the thalamic pulvinar ipsilateral to the painful challenge (x,y, z, −8, −24, 8; …

    • science.sciencemag.org/content/299/5610/1240.full

    DOI: 10.1126/science.1078546

  • Constitutive μ-Opioid Receptor Activity Leads to Long-Term …

    Pain and Dependence. The properties and functions of µ-opioid receptors have been studied intensively with respect to the binding of endogenous or exogenous ligands. However, much less is known about the constitutive, ligand-independent, activation of opioid receptors. Working in mice, Corder et al. (p. 1394) observed …

    • science.sciencemag.org/user/logout?current=node/494607
  • Even more pain in opioid treatment | Science

    Jul 8, 2016  Amid heightened concern about the addictive properties of opiates used to manage pain, new results from Grace et al. reveal that morphine can actually promote chronic pain. Rats with nerve damage treated for 5 days with morphine showed a sensitization to pain that persisted for months after opioid …

    • science.sciencemag.org/content/353/6295/134.3

    DOI: 10.1126/science.353.6295.134-c

  • REPORTS

    The opioid peptide dynorphin, circadian rhythms, and starvation …

    Abstract. Dynorphin, an opioid peptide whose functions are unknown, is found in brain, pituitary, and peripheral organs. Specific radioimmunoassays were used to measure dynorphin in the hypothalamus and pituitary, during the day and at night, as a function of food and water deprivation. Immunoreactive dynorphin was …

    • science.sciencemag.org/content/219/4580/71

    DOI: 10.1126/science.6129699

  • EDITORS’ CHOICE

    Regulating Opioid Responses | Science Signaling

    Different drugs of abuse are thought to hijack similar reward systems in the brain using common mechanisms. However, Koo et al. now observe that some of the neural mechanisms that regulate opiate reward can be both different and even opposite to those that regulate reward by stimulant drugs. Whereas knockdown of …

    • stke.sciencemag.org/content/5/245/ec264?intcmp=trendmd-stke

    DOI: 10.1126/scisignal.2003665

  • REPORTS

    Opioid receptors undergo axonal flow | Science

    Abstract. Previous studies have indicated the presence of opiate receptors on axons of the rat vagus nerve and on other small diameter fibers. In examinations of the effect of ligation on the distribution of receptors in the vagus nerve by in vitro labeling light microscopic autoradiography, a large buildup of receptors was found …

    • science.sciencemag.org/content/210/4465/76

    DOI: 10.1126/science.6158097

  • REPORTS

    Opioid peptides may excite hippocampal pyramidal neurons by …

    Abstract. The atypical excitation by opiates and opioid peptides of hippocampal pyramidal cells can be antagonized by iontophoresis of naloxone, the gamma-aminobutyric acid antagonists bicuculline, or magnesium ion. The recurrent inhibition of these cells evoked by transcallosal stimulation of the contralateral …

    • science.sciencemag.org/content/205/4404/415

    DOI: 10.1126/science.451610

Calorie restricted diet to live long and healthy

Not only did their calorie restricted diet ( CR) monkeys look remarkably younger – with more hair, less sag, and brown instead of grey – than monkeys that were fed a standard diet, they were healthier on the inside too, free from pathology.

Cancers, such as the common intestinal adenocarcinoma, were reduced by over 50%. The risk of heart disease was similarly halved.

And while 11 of the ad libitum (“at one’s pleasure,” in Latin) monkeys developed diabetes and five exhibited signs that they were pre-diabetic, the blood glucose regulation seemed healthy in all CR monkeys. For them, diabetes wasn’t a thing.

Overall, only 13% of the monkeys in the CR group had died of age-related causes in 20 years. In the ad libitum group, 37% had died, nearly three times as many. In an update study from the University of Wisconsin in 2014, this percentage remained stable.

The idea that what a person eats influences their health no doubt predates any historical accounts that remain today. But, as is often the case for any scientific discipline, the first detailed accounts come from Ancient Greece. Hippocrates, one of the first physicians to claim diseases were natural and not supernatural, observed that many ailments were associated with gluttony; obese Greeks tended to die younger than slim Greeks, that was clear and written down on papyrus.

Spreading from this epicentre of science, these ideas were adopted and adapted over the centuries. And at the end of the 15th Century, Alvise Cornaro, an infirm aristocrat from a small village near Venice in Italy, turned the prevailing wisdom on its head, and on himself.

If indulgence was harmful, would dietary asceticism be helpful? To find out, Cornaro, aged 40, ate only 350g (12oz) of food per day, roughly 1000 calories according to recent estimates. He ate bread, panatela or broth, and eggs. For meat he chose veal, goat, beef, partridge, thrush, and any poultry that was available. He bought fish caught from the local rivers.

Restricted in amount but not variety, Cornaro claimed to have achieved “perfect health” up until his death more than 40 years later. Although he changed his birthdate as he aged, claiming that he had reached his 98th year, it is thought that he was around 84 when he died – still an impressive feat in the 16th Century, a time when 50 or 60 years old was considered elderly. In 1591, his grandson published his posthumous three-volume tome entitled “Discourses on the Sober Life,” pushing dietary restriction into the mainstream, and redefining ageing itself.

With an additional boost of health into the evening of life, the elderly, in full possession of their mental capacities, would be able to put decades of amassed knowledge to good use, Carnaro claimed. With his diet, beauty became the aged, not the youthful.

Longevity trials

Cornaro was an interesting man but his findings are not to be taken as fact by any branch of science. Even if he was true to his word and did not suffer ill health for nearly half a century, which seems unlikely, he was a case study of one – not representative of humans as a whole.

But since a foundational study in 1935 in white rats, a dietary restriction of between 30-50% has been shown to extend lifespan, delaying death from age-related disorders and disease. Of course, what works for a rat or any other laboratory organism might not work for a human.

(Credit: Getty Images)

It may sound obvious, but what you choose to put in your trolley can have a profound effect on the length and quality of your life (Credit: Getty Images)

Long-term trials, following humans from early adulthood to death, are a rarity. “I don’t see a human study of longevity as something that would be a fundable research programme,” says Mattison. “Even if you start humans at 40 or 50 years old, you’re still looking at potentially 40 or 50 more years [of study].” Plus, she adds, ensuring that extraneous factors – exercise, smoking, medical treatments, mental wellbeing – don’t influence the trial’s end results is near impossible for our socially and culturally complex species.

That’s why, in the late 1980s, two independent long-term trials – one at NIA and the other at the University of Wisconsin – were set up to study calorie restriction and ageing in Rhesus monkeys. Not only do we share 93% of our DNA with these primates, we age in the same way too.

Slowly, after middle age (around 15 years in Rhesus monkeys) the back starts to hunch, the skin and muscles start to sag, and, where it still grows, hair goes from gingery brown to grey. The similarities go deeper. In these primates, the occurrence of cancer, diabetes, and heart disease increases in frequency and severity with age. “They’re an excellent model to study ageing,” says Rozalyn Anderson, a gerontologist from the University of Wisconsin.

Sherman is the oldest Rhesus monkey ever recorded, nearly 20 years older than the average lifespan for his species in captivity

And they’re easy to control. Fed with specially made biscuits, the diets of the 76 monkeys at the University of Wisconsin and the 121 at NIA are tailored to their age, weight, and natural appetite. All monkeys receive the full complement of nutrients and minerals that their bodies crave. It’s just that half of the monkeys, the calorie restricted (or CR) group, eat 30% less.

They are far from malnourished or starving. Take Sherman, a 43-year-old monkey from NIA. Mattison says that since being placed on the CR diet in 1987, aged 16, Sherman hasn’t shown any overt signs of hunger that are well characterised in his species.

Rhesus monkeys given a stricter, low calorie diet lived longer (Credit: Getty Images)

Rhesus monkeys given a stricter, low calorie diet lived longer (Credit: Getty Images)

Sherman is the oldest Rhesus monkey ever recorded, nearly 20 years older than the average lifespan for his species in captivity. As younger monkeys were developing diseases and dying, he seemed to be immune to ageing. Even into his 30s he would have been considered an old monkey, but he didn’t look or act like one.

The same is true, to varying extents, for the rest of his experimental troop at NIA. “We have a lower incidence of diabetes, and lower incidence of cancer in the CR groups,” says Mattison. In 2009, the University of Wisconsin trial published similarly spectacular results.

Not only did their CR monkeys look remarkably younger – with more hair, less sag, and brown instead of grey – than monkeys that were fed a standard diet, they were healthier on the inside too, free from pathology. Cancers, such as the common intestinal adenocarcinoma, were reduced by over 50%. The risk of heart disease was similarly halved. And while 11 of the ad libitum (“at one’s pleasure,” in Latin) monkeys developed diabetes and five exhibited signs that they were pre-diabetic, the blood glucose regulation seemed healthy in all CR monkeys. For them, diabetes wasn’t a thing.

Overall, only 13% of the monkeys in the CR group had died of age-related causes in 20 years. In the ad libitum group, 37% had died, nearly three times as many. In an update study from the University of Wisconsin in 2014, this percentage remained stable.

The results show that ageing itself is a reasonable target for clinical intervention and medical treatment – Rozalyn Anderson

“We have demonstrated that ageing can be manipulated in primates,” says Anderson. “It kind of gets glossed over because it’s obvious, but conceptually that’s hugely important; it means that ageing itself is a reasonable target for clinical intervention and medical treatment.”

If ageing can be delayed, in other words, all of the diseases associated with it will follow suit. “Going after each disease one at a time isn’t going to significantly extend lifespan for people because they’ll die of something else,” says Anderson. “If you cured all cancers, you wouldn’t offset death due to cardiovascular disease, or dementia, or diabetes-associated disorders. Whereas if you go after ageing you can offset the lot in one go.”

Calorie restriction involves a permanent reduction in a diet (Credit: Getty Images)

Calorie restriction involves a permanent reduction in a diet (Credit: Getty Images)

Eating less certainly seemed to help the monkeys, but calorie restriction is much tougher for people out in the real world. For one, our access to regular, high-calorie meals is now easier than ever; with companies like Deliveroo and UberEats, there is no longer a need to walk to the restaurant anymore. And two, gaining weight simply comes more naturally to some people.

“There’s a huge genetic component to all of this and its much harder work for some people than it is for others to stay trim,” says Anderson. “We all know someone who can eat an entire cake and nothing happens, they look the exact same. And then someone else walks past a table with a cake on it and they have to go up a pant size.”

Ideally, the amount and types of food we eat should be tailored to who we are – our genetic predisposition to gaining weight, how we metabolise sugars, how we store fat, and other physiological fluxes that are beyond the scope of scientific instruction at the moment, and perhaps forever.

But a predisposition to obesity can be used as a guide to life choices rather than an inevitability. “I personally have a genetic history of obesity running through my family, and I practice a flexible form of caloric restriction,” says Susan Roberts a dietary scientist at Tufts University in Boston. “I keep my BMI at 22, and [have calculated] that that requires eating 80% of what I would eat if my BMI was at 30 like every other member of my family.” Roberts stresses that it isn’t hard – she follows her own weight management programme using a tool called iDiet to help her eat less but avoid feeling hungry or deprived of enjoyment. If this wasn’t possible, she adds, she wouldn’t practise calorie restriction.

Not only has Roberts seen the problems of obesity first-hand in her family, she knows the benefits of CR better than most. For over 10 years she has been a leading scientist in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy trial, also known as Calerie. Over two years, 218 healthy men and women aged between 21 and 50 years were split into two groups.  In one, people were allowed to eat as they normally would (ad libitum), while the other ate 25% less (CR). Both had health checks every six months.

Unlike in the Rhesus monkey trials, tests over two years can’t determine whether CR reduces or delays age-related diseases. There simply isn’t enough time for their development. But the Calerie trials tested for the next best thing: the early biological signs of heart disease, cancer, and diabetes.

Published in 2015, the results after two years were very positive. In the blood of calorie-restricted people, the ratio of “good” cholesterol to “bad” cholesterol had increased, molecules associated with tumour formation – called tumour necrosis factors (TNFs) – were reduced by around 25%, and levels of insulin resistance, a sure sign of diabetes, fell by nearly 40% compared to people who ate their normal diets. Overall, the blood’s pressure was lower.

Significant health benefits may be garnered in an already healthy body, but further trials are needed

Admittedly, some benefits may come from weight-loss. Earlier trials from Calerie had included people that were obese as well as those with a healthy body mass index (BMI) of 25 or below, and slimming down would have certainly improved the welfare of the heavier participants. “One thing that’s been very clear for a long time is that being overweight or obese is bad for you,” says Roberts. Diseases and disorders previously thought to be age-associated diseases are now popping up in the obese population, she adds.

But the latest results suggested that significant health benefits can be garnered in an already healthy body – a person who isn’t underweight or obese. That is, someone whose BMI lies between 18.5 and 25.

Gut microbes signal to the brain when they are full

Don’t have room for dessert? The bacteria in your gut may be telling you something. Twenty minutes after a meal, gut microbes produce proteins that can suppress food intake in animals, reports a study published November 24 in Cell Metabolism. The researchers also show how these proteins injected into mice and rats act on the brain reducing appetite, suggesting that gut bacteria may help control when and how much we eat.

The new evidence coexists with current models of appetite control, which involve hormones from the gut signalling to brain circuits when we’re hungry or done eating. The bacterial proteins–produced by mutualistic E. coli after they’ve been satiated–were found for the first time to influence the release of gut-brain signals (e.g., GLP-1 and PYY) as well as activate appetite-regulated neurons in the brain.

“There are so many studies now that look at microbiota composition in different pathological conditions but they do not explore the mechanisms behind these associations,” says senior study author Sergueï Fetissov of Rouen University and INSERM’s Nutrition, Gut & Brain Laboratory in France. “Our study shows that bacterial proteins from E. coli can be involved in the same molecular pathways that are used by the body to signal satiety, and now we need to know how an altered gut microbiome can affect this physiology.”

Mealtime brings an influx of nutrients to the bacteria in your gut. In response, they divide and replace any members lost in the development of stool. The study raises an interesting theory: since gut microbes depend on us for a place to live, it is to their advantage for populations to remain stable. It would make sense, then, if they had a way to communicate to the host when they’re not full, promoting host to ingest nutrients again.

In the laboratory, Fetissov and colleagues found that after 20 minutes of consuming nutrients and expanding numbers, E. coli bacteria from the gut produce different kinds of proteins than they did before their feeding. The 20 minute mark seemed to coincide with the amount of time it takes for a person to begin feeling full or tired after a meal. Excited over this discovery, the researcher began to profile the bacterial proteins pre- and post-feeding.

They saw that injection of small doses of the bacterial proteins produced after feeding reduced food intake in both hungry and free-fed rats and mice. Further analysis revealed that “full” bacterial proteins stimulated the release of peptide YY, a hormone associated with satiety, while “hungry” bacterial hormones did not. The opposite was true for glucagon-like peptide-1 (GLP-1), a hormone known to simulate insulin release.

The investigators next developed an assay that could detect the presence of one of the “full” bacterial proteins, called ClpB in animal blood. Although blood levels of the protein in mice and rats detected 20 minutes after meal consumption did not change, it correlated with ClpB DNA production in the gut, suggesting that it may link gut bacterial composition with the host control of appetite. The researchers also found that ClpB increased firing of neurons that reduce appetite. The role of other E.coli proteins in hunger and satiation, as well as how proteins from other species of bacteria may contribute, is still unknown.

Diagram of nutrient-induced E.coli growth in the gut on feeding behavior.

“We now think bacteria physiologically participate in appetite regulation immediately after nutrient provision by multiplying and stimulating the release of satiety hormones from the gut,” Fetisov says. “In addition, we believe gut microbiota produce proteins that can be present in the blood longer term and modulate pathways in the brain.”

ABOUT THIS NEUROSCIENCE RESEARCH

Funding: This work received support from the EU INTERREG IVA 2 Seas Program; Haute-Normandie Region, France; and the Marie Curie CIG NeuROSens.

Source: Joseph Caputo – Cell Press
Image Credit: The images are credited to J. Breton, N. Lucas & D. Schapman and Breton et al./Cell Metabolism 2015
Original Research: Abstract for “Gut Commensal E. coli Proteins Activate Host Satiety Pathways following Nutrient-Induced Bacterial Growth” by Jonathan Breton, Naouel Tennoune, Nicolas Lucas, Marie Francois, Romain Legrand, Justine Jacquemot, Alexis Goichon, Charlène Guérin, Johann Peltier, Martine Pestel-Caron, Philippe Chan, David Vaudry, Jean-Claude do Rego, Fabienne Liénard, Luc Pénicaud, Xavier Fioramonti, Ivor S. Ebenezer, Tomas Hökfelt, Pierre Déchelotte, and Sergueï O. Fetissov in Cell Metabloism. Published online November 24 2015 doi:10.1016/j.cmet.2015.10.017


Abstract

Gut Commensal E. coli Proteins Activate Host Satiety Pathways following Nutrient-Induced Bacterial Growth

The composition of gut microbiota has been associated with host metabolic phenotypes, but it is not known if gut bacteria may influence host appetite. Here we show that regular nutrient provision stabilizes exponential growth of E. coli, with the stationary phase occurring 20 min after nutrient supply accompanied by bacterial proteome changes, suggesting involvement of bacterial proteins in host satiety. Indeed, intestinal infusions of E. coli stationary phase proteins increased plasma PYY and their intraperitoneal injections suppressed acutely food intake and activated c-Fos in hypothalamic POMC neurons, while their repeated administrations reduced meal size. ClpB, a bacterial protein mimetic of α-MSH, was upregulated in the E. coli stationary phase, was detected in plasma proportional to ClpB DNA in feces, and stimulated firing rate of hypothalamic POMC neurons. Thus, these data show that bacterial proteins produced after nutrient-induced E. coli growth may signal meal termination. Furthermore, continuous exposure to E. coli proteins may influence long-term meal pattern.

“Gut Commensal E. coli Proteins Activate Host Satiety Pathways following Nutrient-Induced Bacterial Growth” by Jonathan Breton, Naouel Tennoune, Nicolas Lucas, Marie Francois, Romain Legrand, Justine Jacquemot, Alexis Goichon, Charlène Guérin, Johann Peltier, Martine Pestel-Caron, Philippe Chan, David Vaudry, Jean-Claude do Rego, Fabienne Liénard, Luc Pénicaud, Xavier Fioramonti, Ivor S. Ebenezer, Tomas Hökfelt, Pierre Déchelotte, and Sergueï O. Fetissov in Cell Metabloism. Published online November 24 2015 doi:10.1016/j.cmet.2015.10.017

Hunger has stronger motivational force than fear, anxiety or thirst

Hunger is a strong motivational force, with the capacity to curb rival drives states such as thirst, anxiety, fear of predators, and social needs, according to a study in mice published September 29 in Neuron. The researchers also found that activation of neurons known to regulate appetite mimics the state of hunger in mice, suppressing competing motivational systems in the presence of food. The findings shed light on how the brain integrates rival drive states to guide motivated behavior in natural environments.

“This study suggests our motivations are more highly interrelated than neuroscientists often think,” says senior study author Michael Krashes of National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. “Therefore, studying isolated motivated behaviors may not accurately demonstrate how the big picture nervous system works. Our study is one of the first steps to investigating feeding behavior in a more complicated, naturalistic setting.”

Animals including humans engage in numerous motivated behaviors in the natural world and often need to adjust how they behave to adapt to different situations. However, neuroscientists often study these behaviors one at a time and in tightly controlled experimental settings. Therefore, it has not been clear how different drive states compete with one another, and what underlying neural circuits are involved.

To address these questions, Krashes and his team combined an array of behavioral assays with optogenetics to assess the role of agouti-related peptide (AgRP) neurons in integrating rival motivational systems. These neurons, located in an evolutionarily conserved brain structure called the hypothalamus, are known to drive feeding behavior and are critical for survival.

Through a series of experiments, the researchers found that hunger may be at the peak of the motivation hierarchy, and that AgRP neurons play a key role in motivating hunger-driven behavior in the presence of competing drive states. In one set of experiments, mice that were both thirsty and hungry, either due to being deprived of access to food for 24 hours or AgRP activation, consumed more food at the expense of drinking water, compared with mice that were thirsty but not hungry. “We interpret this as a unique ability of hunger-tuned neurons to anticipate the benefits of searching for food, and then alter behavior accordingly,” Krashes says.

Hunger even overrides anxiety-like behavior and the fear of predators. Hunger, or hunger-mimicking AgRP activation, motivated mice to spend more time in fear-evoking locations–such as the open center of a large arena or a chamber scented with a chemical produced by foxes–when food was present at those locations. By contrast, sated mice preferred to stay in “safe” corner zones or in a non-scented chamber rather than venture out into the more risky locations.

Additional experiments revealed that hunger also trumps social needs when food is available. Hunger, or AgRP activation, increased the preference of socially isolated mice to spend time in a chamber containing food rather than a different chamber containing another mouse. Meanwhile, mice that were socially isolated but sated strongly preferred the company of another mouse to a chamber baited with food.

However, AgRP activity increased when another mouse was nearby, suggesting that these neurons may respond to the presence of potential competitors for food. “We think that the presence of another mouse could be viewed as competition for limited resources, increasing the motivation to seek food, which is a finding that no other studies have indicated thus far,” Krashes says.

In future studies, the researchers plan to examine how AgRP neurons communicate with other brain regions during motivated behaviors. “These interrelationships are highly complicated and further work will need to delve much more deeply into understanding how these interrelationships work on the neural level,” Krashes says.

In the meantime, the new findings have important evolutionary implications, Krashes says. “Our continued existence, among that of other species, has motivated us to pursue an array of behaviors, all governed by our nervous system,” he says. “Of course, we can’t pursue all those motivations at once, so we have had to choose which ones were most important during different times of need. Evolutionarily speaking, animals that consistently picked the right motivations over others have survived while other animals have not.”

Source:

Cell Press


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Neurons ‘Predict’ Drinking’s Restorative Effects Well Before They Unfold

By Leigh Beeson

A new UC San Francisco study shows that specialized brain cells in mice “predict” the hydrating effects of drinking, deactivating long before the liquids imbibed can actually change the composition of the bloodstream. The results stand in stark contrast to current views of thirst regulation, which hold that the brain signals for drinking to stop when it detects liquid-induced changes in blood concentration or volume.

Thirst neurons, located in the subfornical organ (SFO) of the brain, do make us thirsty when they sense that blood volume has dipped or when blood becomes too concentrated. But the same signaling mechanism can’t operate in reverse to alert us to stop drinking because thirst is satiated too soon after a person begins to drink, said UCSF’s Zachary Knight, PhD, senior author of the study, which appears in the August 3, 2016 issue of Nature. Nor can current theories explain why we usually like to drink something while we eat.

“You drink a glass of water and you instantly feel like your thirst is quenched, but it actually takes tens of minutes for that water to reach your blood,” said Knight, assistant professor of physiology. “You eat something salty and you instantly beginning to feel thirsty even though that food is just in your mouth. The dominant model that thirst is a response to changes in the blood didn’t explain that.”

After employing a technique that causes specific, targeted populations of neurons in the mouse brain to fluoresce brightly when active, they used fiber optic probes to measure the activity of SFO neurons when mice drank water. They found that SFO neuron activity shut off almost immediately after the mice started to drink and that the mice stopped drinking shortly thereafter. The brief time scale of these events suggests that, rather than acting only as monitors of blood composition, the SFO must also be linked to sensors in the mouth and throat that rapidly detect food and water consumption.

To confirm the relationship between oral-cavity sensors and SFO neurons, the research group deprived the mice of water overnight and used optogenetic methods – in which particular cells are genetically altered so light delivered via fiber optics can activate or inhibit those cells — to shut down SFO neuron activity when they were again given access to water. Despite the water deprivation, and the presumed changes in the blood that would cause, the mice didn’t drink. But as soon as the researchers stopped silencing the SFO neurons, the mice drank copiously.

The researchers used similar methods to explore why eating often prompts people to drink and why a drink’s temperature affects how refreshing we find it.

“When you sit down at a meal, it’s such a universal experience to have a beverage with you, and we’ve never understood why that is — why you take a bite of food and then take a drink of water,” said Christopher Zimmerman, lead author of the study and a UCSF Discovery Fellow in the Knight laboratory. “And almost everyone has had the experience of exercising or doing some sort of activity and becoming really thirsty, and almost viscerally feeling better after drinking a cold glass of water. But why does cold water seem to quench your thirst so much more rapidly?”

To answer the first question, mice that went without food for a night were given food the following morning but no water. SFO neurons lit up almost immediately as the mice began to eat. Mice who were allowed both food and water also experienced the increase in thirst neuron activity, and when the researchers tamped down the neurons’ activity, the mice reduced their water consumption (though they continued to eat).

When mice were given access to water bottles of varied temperatures, the researchers found that although all the mice drank enough water to turn off their SFO neurons, it required significantly fewer licks to deactivate SFO neurons if the water the mice drank was cold. The scientists zeroed in on temperature as a crucial factor in SFO activity by applying cold metal, similar to that found on animal water-bottle droppers, to the mice’s mouths. This proved as effective as cold water in shutting down the activity of SFO cells.

The new study is an extension of Knight’s previous work on hunger neurons in mice, for which he was awarded a National Institutes of Health New Innovator Award in 2015. In that research his team used similar techniques to record the activity of hunger neurons in mice for the first time and showed that these neurons shut off in response to the sight and smell of food well before the mice actually consumed anything — a surprising finding that parallels those in the new Nature study — just as thirst neurons “anticipate” the bodily changes that drinking will produce, hunger neurons shut down long before mice are actually satiated by eating.

The study was co-authored by Yen-Chu Lin, Erica Huey, and Gwendolyn Daly, research specialists in the Knight Lab, as well as David Leib, Ling Guo and Yiming Chen, students in the UCSF Neuroscience Graduate Program. The study was funded by a UCSF Discovery Fellowship, the New York Stem Cell Foundation, the the American Diabetes Association, Rita Allen Foundation, the McKnight Foundation, the Alfred P. Sloan Foundation, the Brain and Behavior Research Foundation, the Esther A. and Joseph Klingenstein Foundation, the Program for Breakthrough Biomedical Research, an NIH New Innovator Award, the UCSF Diabetes and Obesity Centers, and grants from the National Science Foundation and the National Institutes of Health.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences; and a preeminent biomedical research enterprise. It also includes UCSF Health, which comprises two top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospital San Francisco, and other partner and affiliated hospitals and healthcare providers throughout the Bay Area.

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