Obesity Threatens Cardiovascular Health Gains, Longevity
You saw in the Chapter 5 Updates that drug overdoses are the major contributor to the recent two years of longevity decline; rising obesity is also taking its toll. The past 50 years has seen a decline in cardiovascular deaths in Europe and surrounding countries, but those gains may be halted by increasing obesity. In a survey of the 56 European, North African, and Middle Eastern countries participating in the European Society of Cardiology, type 2 diabetes doubled from 2 to 4 per cent between 1995 and 2014, and is 5 per cent in the wealthier countries, where cardiovascular health gains have been greatest. The obesity rate is also highest in the high income countries, at 23 per cent; UK has the highest rate among men, at 27 per cent, and second highest among women, at 29%. European Heart Journal, Vol 39, 508-579.

Dopamine Could Treat Diabetes
We knew that dopamine released in the ventral striatum, an area important in reward (see p 173 of the text), plays a key role in regulating glucose levels in mice, but this pathway had not been seen in humans. Then when a 53-year-old Dutch man received deep brain stimulation (DBS) in the ventral striatum to treat his obsessive-compulsive disorder, his type 2 diabetes improved so much that he was able to get by with 20% less insulin. Several years later, Mireille Serlie and her team turned off DBS in the man and in 14 OCD patients without diabetes; in all 15 insulin sensitivity increased, which means that their cells were better able to take glucose from the bloodstream. They tested the stimulation results in mice; cells in their bodies increased their absorption of glucose. Using DBS to treat diabetes isn't practical, so the team tried giving 10 healthy men a drug that depletes dopamine; as a result, the men's insulin sensitivity decreased. Insulin treatment has the disadvantage that the patient requires more and more insulin, so these results suggest a hopeful new approach. Science Translational Medicine, DOI: 10.1126/scitranslmed.aar3752.

New Roles for Hunger Hormones
One way gut hormones influence hunger is by modulating dopamine in the reward system. But according to panelists at the 2018 annual meeting of the Society for the Study of Ingestive Behavior, they also affect drug taking. For example, ghrelin, a hunger hormone released by the stomach, can also influence the reward value of drugs; in people with alcohol use disorder it promotes alcohol seeking. The hormones GLP-1 and amylin signal food satiety, and medications that enhance their action also reduce the rewarding effects of drugs and alcohol. Medications that affect GLP-1 and amylin are already FDA approved for treating type 2 diabetes and obesity and could be repurposed for treating addictions. Science Daily, July 17, 2018.

Monitoring Sugar Level in Diabetics' Tears
Monitoring blood sugar level is necessary for diabetics to avoid high levels that could damage organs, and researchers are constantly looking for alternatives to repeatedly pricking fingers to check the blood. Strategies include attempting to detect sugar in the sweat or saliva, and the US Food and Drug Administration recently approved a patch with a small wire inserted under the skin, which sends data to a smart phone or computer. Perhaps the most intriguing effort to date involves a contact lens containing a glucose sensor; the sugar content of the tears corresponds closely to blood sugar. A small LED mounted at the edge of the lens is ordinarily illuminated and turns off when the sugar level rises. The wearer simply looks in the mirror to check the light, which looks like a small piece of glitter. Science Advances, Vol. 4, no. 1, eaap9841 (online).

How Many Kinds of Diabetes?
We have considered diabetes as either something you're born with (type 1) or something you get later in life from eating too much (type 2), but the two types can occur at various life stages and for a variety of reasons. Using measures of age, BMI, blood sugar, and insulin production and sensitivity of 15,000 participants in Sweden and Finland, researchers have identified five variations, apparently the result of lifestyle and genetic differences. It is likely this number will increase with similar studies of other ethnic and cultural groups. Diagnosing the specific type could help doctors plan more effective individual treatments. Lancet Diabetes and Endocrinology, Vol 6, 361-369.

How AgRP Neurons Induce Eating
Agouti-related protein (AgRP) neurons in the hypothalamus increase eating and reduce metabolism (see p 156 in the text). By imaging activity in individual cells in the insular cortex of mice, neuroscientists have determined that the insula is a target of AgRP neuronal output, via pathways through the paraventricular nucleus and the basolateral amygdala. The amygdala plays a role in determining the value of food-related clues; the insula seems to determine whether a source of food is worth pursuing. One evidence of the latter is that food cues increase insular activity in hungry animals, but not when they are sated. Stimulating AgRP neurons restored responses to visual food cues in sated mice and caused them to seek more food. Current Obesity Reports, Vol 7, 122-129.

Being Hungry Might Be Good For Your Brain
Injecting the hunger-inducing hormone ghrelin into mice improves their performance in learning and memory tests; mice fed low-calorie diets also perform better, and people often report that they feel sharper after fasting. Now researchers at Swansea University in the UK have discovered that adding ghrelin to mouse brain cells grown in a dish switches on a gene called fibroblast growth factor, which is known to trigger neurogenesis. The work was presented at a recent British Neuroscience Association conference. Reported in New Scientist, April, 2017.

Hunger-Related Circuit Suppresses Pain
Our needs operate in hierarchies; acute pain, which signals danger, suppresses hunger, but 24 hours without food will cause a rat to stop licking its inflamed and painful paw. Now we know how hunger trumps non-emergency pain. Stimulation of agouti-related protein (AgRP) neurons in the hypothalamus not only increases hunger (see p 156 in the text), but in a study with mice it also suppressed pain-induced paw licking. Stimulating a subset of AgRP neurons that project to the parabrachial nuclei in the pons produced a strikingly greater pain suppression, comparable to that from opiates like morphine. Stimulation of those neurons did not induce hunger, suggesting that their effect is pain specific, rather than distracting the animal with hunger. Starvation isn't a good option for treating pain, but knowledge of this circuit could lead to pain treatments that are safer than opiates. Cell, 173, 140-152.e15.

Reactions to Sweet and Bitter Occur in the Amygdala
We distinguish between the taste qualities of sweet, bitter, salty, sour, and umami because specialized receptors send discrete signals over "dedicated lines" to distinctly separate areas in the cortex. But survival requires that we also respond to the valence of the tastants, which leads us to approach some and avoid others. This is mostly unlearned; but how does the brain do it?. We now have an answer, at least for sweet and bitter. Researchers have just discovered that neurons from the cortical areas for sweet and bitter project to separate areas of the amygdala; by stimulating these pathways individually the researchers could make mice respond to water as if it were sweet and to make sweet aversive or bitter attractive. As a further demonstration that these pathways are required for determining valence judgements, the researchers blocked the amygdala; the mice were still able to distinguish the tastes, but no longer made emotional distinctions between sweet and bitter. Nature, Vol 558, 127-131.

Stronger Evidence for a Virus in Obesity
Research has suggested that adenovirus-36, a virus which causes respiratory and eye infections in humans, can also cause obesity, but the studies have assessed antibodies to the virus, not the virus itself. Now, researchers using tissue from breast biopsies have found the virus in tissue of 81% of obese women, compared to 19% of samples from healthy-weight women. This rasises the possibility that some cases of obesity might be treated with a vaccine. The work was presented at a conference of the American Society for Microbiology and reported in the Daily Telegraph (Australia), Aug 4, 2018.

Link Between Sleep and Hunger Strengthened
There is evidence that sleep loss contributes to hunger and obesity; this evidence is correlational, although it is bolstered by the finding that sleep loss reduces leptin levels and increases ghrelin production (text, p 163). Now there is stronger support from a study that manipulated the sleep variable. Volunteers were given advice on ways to get more sleep, such as avoiding caffeine and not going to bed either hungry or too full. Eighty-five percent spent more time in bed and half slept longer than before, resulting in a 10-gram daily increase in sugar consumption (equivalent to more than 4 cubes of sugar). Members of the control group showed no significant changes in diet. American Journal of Clinical Nutrition, Vol 107, 43-53.