Fat Chance: The bitter truth about sugar. Dr. Lustig Robert

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СКАЧАТЬ 4 percent of total sales of food outside the home. In 1997 it accounted for 34 percent. Each day, 30 percent of U.S. adults eat at a fast food outlet, and McDonald’s feeds forty-six million Americans.

      What about the rest of the world? They didn’t experience fast food growing up, yet it’s now the biggest seller in developing countries. There is no familiarity here; they weren’t raised on the stuff; they’re consuming it de novo. Why do they eat fast food when it’s not their traditional fare? Because it’s cheap? It certainly isn’t abroad. Why do the locals frequent Taco Bell in Mexico when the original tacos are cheaper and ostensibly healthier? Something more is going on here. Is the world addicted to fast food? The biology of addiction is at the center of this question.

       Might as Well Face It, We’re Addicted to…

      Our brains are wired for reward—it is the primary force behind human survival. Reward is the reason to get up in the morning. If you take away reward, you take away the reason to live. We know this from recent experience with the anti-obesity drug rimonabant, which was deep-sixed after it failed to gain approval from the FDA in 2007. Rimonabant is an endocannabinoid antagonist, or the “anti-marijuana” medicine—which means it’s also “anti-munchies.” It inhibits the sense of reward. While it worked to promote weight loss, 20 percent of the subjects who used it experienced serious psychiatric side effects, especially depression, and there were several suicides. Kill the reward system, and you just might want to kill yourself.

      Although the brain’s reward system is complex and has many inputs, it can be reduced to the “hedonic pathway.” This pathway is where primal emotions, reproductive drive, and the survival instinct are all housed and expressed. These reward mechanisms are thought to have evolved to reinforce behaviors that are essential for perpetuation of the species and survival: such as sex for reproduction and the enjoyment of food so that you eat. This is also the pathway that reinforces the positive and negative aspects of drugs of abuse such as nicotine, cocaine, morphine, and alcohol. In order to maintain eating as one of the most powerful urges in animal and human behavior, evolution has also made it a rich source of pleasure and reward.

      The hedonic pathway comprises a neural conduit between two brain areas: the ventral tegmental area (VTA) and the nucleus accumbens (NA, also known as the reward center), both of which are deep-brain structures. Pleasure occurs when the VTA signals the NA to release dopamine, a neurotransmitter. It’s a signal from one brain center to another. When the released dopamine binds to its specific dopamine D₂ receptor in the NA, the sense of pleasure is experienced.¹

      So what are neurotransmitters and receptors? Think of keys and locks. Each neuron is a cell body, and at its end is an axon (special fiber of the neuron that sends information). This axon has a synapse, or pathway, that connects to the dendrites (specialized fibers of the nerve cell that receive information) of the next neuron. When a neural impulse is generated in the first cell, it pulses down to the end of the axon, which contains little packets of neurotransmitters that are then released. These are the keys. They travel across the synapse to the receptors (locks), located in the dendrites of the next cell. There are many keys that take the path along the synapse, and not all of them make it to their destination. Along their way via the synapse, some are metabolized and some are “re-uptaken.” Dopamine is one of these types of keys traveling to fit into the locks of the D₂ receptors in the next cell, thus determining the triggering and firing of the next cells down the chain.

      Food intake is just one readout of the hedonic pathway.² It appears to mediate feeding on the basis of palatability rather than energy need: I’m stuffed, but that chocolate cake looks so good. When functional, the hedonic pathway helps to curtail food intake in situations where energy stores are replete: I don’t need to finish that macaroni and cheese. However, when dysfunctional, this pathway can increase food intake, leading to obesity.

      If you feed a rodent a palatable food (e.g., a high-fat, high-sugar food such as cookie dough), the animal experiences reward because dopamine is released from the VTA and binds to the D₂ receptor in the NA. As long as that continues, the animal will continue to eat and experience reward. There are three processes that modulate this system in one direction or another:

      1. Anything that increases the dopamine transmission to the NA increases the feeling of reward.

      2. Anything that clears dopamine from the NA will extinguish the feeling of reward.

      3. Anything that reduces the number of D₂ receptors in the NA, or binding of dopamine to those receptors (such as chronic overuse of a substance), will shortchange reward. You then need more dopamine, and hence more of the substance, to get the same feeling of pleasure.

      These precepts are as true for food as they are for addictive drugs. And food and drugs cross over. With time we can become sensitized to a substance and need more of it to get the same effect. Once sensitized, animals and humans may become hyperresponsive to a new substance; this is known as cross-sensitization. In other words, if the brain has been wired for addiction, it’s easy to switch from one substance to another. Ask recovering alcoholics about their incessant need for coffee, tobacco, and/or sugar. A reinforcer is a stimulus that increases the probability that an animal or human will respond to the addictive drug. Food is a form of positive reinforcement. Dopamine stimulation in the NA reinforces the intake of drugs or alcohol and also of food.

      The reinforcing effect of dopamine is attributed to D₂ receptor stimulation. As stated before, food intake increases as a result of morphine and marijuana use. The film Harold and Kumar Go to White Castle details the odyssey of two very stoned guys who seek to overcome seemingly insurmountable obstacles in their quest for a hamburger. We can measure this by dopamine release and D₂ receptor signaling. Why does dopamine matter so much? In a normal person, dopamine will be cleared from the D₂ receptors after he is satiated. If you have a decreased dopamine binding capacity, there is a perceived need for compulsive food intake to provide excess stimulation of these depressed circuits, thereby driving continued weight gain.

       The Usual Suspects: Leptin and Insulin

      Yup, them again. Not only are they central in the starvation response, but they are also key players in this hedonic pathway, modulating reward in response to meals. In normal circumstances, after you’ve eaten a sufficient amount, leptin sends a signal to the VTA to suppress the release of dopamine, thereby reducing the reward of food.³

      So leptin extinguishes reward. But what if you are leptin resistant? That’s what obesity is: leptin resistance. If leptin can’t act, then the dopamine isn’t cleared from the NA, and the impetus for further consumption persists. If you’re leptin resistant, do you really think you have the willpower to ignore both the starvation signal and the reward signal, when every food outlet you pass by provides you with sight or smell cues to chow down? Starvation and reward conspire to thwart every obese person.

      What about insulin, leptin’s accomplice? Normally, people are sufficiently sensitive to insulin. Insulin’s job is to clear dopamine from the synapses (that pathway between the cells) in the NA.⁴ Thus, the rise in insulin that occurs during a meal blunts the reward of further food intake (I’ve eaten enough—I really don’t need a second helping). This acts as a servomechanism built into the hedonic pathway to prevent overfeeding. But what happens when you are insulin resistant? Insulin resistance leads to leptin resistance in the VTA, contributing to increased caloric intake by preventing dopamine clearance from the NA. Increased pleasure is then derived from food when energy stores are full.⁵ Insulin and leptin resistance lead not only to increased food intake but to increased palatable food intake or anything that is high in both fat and sugar: the muffins, the Cinnabons, the cookies, the cheesecake. Is it any wonder Mrs. Fields is in every shopping mall?

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