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

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СКАЧАТЬ in high amounts at baseline, just like the brain tumor kids,¹⁴ and their quality of life improved with the drug.

      There is one final lesson to glean from these studies. All these obese adult subjects had high leptin levels. They were leptin resistant; if their leptin worked right, they wouldn’t have been obese. If leptin falls, the brain should interpret this as starvation and reduce the patient’s resting energy expenditure accordingly. But these patients’ resting energy expenditures went up! And their improvement in energy expenditure correlated with the suppression of their insulin levels, the same as with the brain tumor kids. When we were successful in getting their insulin down, their leptin resistance improved.¹⁵ This suggests that insulin can block leptin signaling in the brain, and therefore insulin acts as a “leptin antagonist.”¹⁶

      Many scientists have now shown that insulin actions in the VMH block leptin signaling.¹⁷ A reduction in insulin concentrations results in a decline in leptin. Insulin and leptin are independent hormones that bind to separate receptors in the VMH. They have their own separate pathways of action, but they share the same signaling cascade. When insulin levels at the VMH are chronically high, leptin cannot signal the hypothalamus.

       Deconstructing Darwin

      Whenever paradoxical events occur in biology, one has to look for an evolutionary explanation. Why should insulin block leptin signaling? What’s the advantage for insulin, the hormone that tells the body to store energy, to block leptin, the hormone that tells your brain to burn energy? Leptin is a necessary signal to the VMH for the initiation of high-energy processes, such as puberty and pregnancy. If leptin always worked right, then nobody could gain weight. Think of the 97-pound weakling at the beach. The crucial weight gain during puberty and pregnancy would be compromised, and our reproductive capacity would be shot. Twice in our lives we need to stop leptin from working, or we can’t gain the weight, and the species dies out. Since insulin drives energy storage, it makes sense that it should do double-duty, and also be the central blocker of leptin—one hormone, two coordinated actions. Indeed, both puberty and pregnancy are hyperinsulinemic states. When adulthood or the postpartum state is reached, the insulin levels fall, weight stabilizes or is lost, and leptin levels return toward baseline.¹⁸ However, in maladaptive conditions, when insulin is high all the time and leptin signaling is impaired, the energy gets stored yet the brain sees starvation, and obesity worsens.

      When you examine the symptoms of obese and starved individuals, they are very similar. On first thought this sounds ludicrous, but it actually makes sense. Both claim fatigue, malaise, and depression. The reason for this in both groups is the inability to adequately respond to the leptin signal—in starvation because of the inadequacy of leptin, and in obesity because of the resistance to leptin. Furthermore, leptin concentrations drop precipitously during periods of short-term fasting (within twelve hours), declining faster than body fat stores. You haven’t lost any weight in that time, but your fat cells are already telling your brain you’re starving, driving your food intake back up. By the time you’re one day into any weight-loss regimen you’re already leptin deficient on top of being leptin resistant, meaning, you really can’t see the signal. Trying not to eat for a day to fit into that little black dress? Oops. This actually drives gluttony and sloth to return your weight to its baseline level. In a nutshell, this is the recidivism of obesity. If your brain thinks there’s no leptin (due to either leptin deficiency or leptin resistance) you’re pretty miserable. Your sympathetic nervous system goes into conservation mode, driving down your energy expenditure, physical activity, and quality of life. Your vagus nerve then goes into overdrive, driving up your appetite, your insulin, and your energy storage.

       The Alternate Interpretation of the First Law

      No matter the mechanism, insulin blocks leptin signaling both in rodents and in humans. In the body, insulin causes energy storage in fat cells. In the brain, insulin causes leptin resistance and “brain starvation.” Insulin delivers a one-two punch to drive gluttony and sloth, weight gain, and obesity the world over. Insulin is the bad guy in this story.

      This idea turns obesity on its head. The standard thinking in obesity is: “If you eat it, you had better burn it, or you’re going to store it”—in which case the weight gain is secondary to the two behaviors of increased energy intake (gluttony) and decreased energy expenditure (sloth). What these data are telling us is that it is the other way around. Storing energy is a biochemical process not under the patient’s control. Burning energy is synonymous with quality of life. Things that make you burn energy faster—such as exercise, ephedrine (off the market now), and caffeine (for about two hours)—make you feel good. Conditions that make you burn energy slower—starvation and hypothyroidism, for example—make you feel lousy. So, the first law needs to be reinterpreted: “If you are going to store it, and you expect to burn it, then you will have to eat it.”¹⁹ In this interpretation, the biochemical process is primary, the weight gain is secondary, and the behaviors are a result of the biochemistry.

      Obesity is a biochemical alteration in the brain promoting leptin resistance with resultant weight gain and secondary changes in behavior to maintain energy balance. The apparent character defects of gluttony and sloth are not the cause of the problem; they are the result of the problem. The biochemistry drives the behavior, not vice versa. The linchpin in this biochemical alteration is the hormone insulin. The majority of humans, regardless of weight, release double the insulin today that we did thirty years ago for the same amount of glucose. Now we’re left with the $147 billion (the annual financial cost of obesity) question: If insulin is the bad guy and we’re all hyperinsulinemic as never before in the history of humankind, where did the excess insulin come from? And how do we reverse it?

      The plot thickens.

       Chapter 5

       Food Addiction—Fact or Fallacy

      Salvador is a fifteen-year-old Latino boy with obesity, a fatty liver, and high blood pressure. He drinks four sodas a day. His mother does not buy them for him or keep them in the house. Rather, he buys them at the convenience store on the way to and from school. Salvador enrolls in our research study whereby each day, for ten days, he will consume the same number of calories from our hospital’s Metabolic Kitchen, which will provide all his food, prepared by a chef and sugar free. Nonetheless, each day, he buys a can of soda and brings it home, putting it on his dresser, next to those from the day before. He tells his mother, “When the study is over, I’m drinking them all.” Indeed, the evening of the end of the study, he drinks every last one, to his mother’s chagrin. He may not have been addicted physically, but the mental obsession and craving indicated dependence, and could not be suppressed.

      Life’s too short to eat bad food, even if it’s cheap. Eating is supposed to be an enjoyable experience, especially when the food is special. There’s nothing quite like going to a nice restaurant with the sights, sounds, and smells of a well-prepared meal. It’s one of the true enjoyments of life. Yet familiarity breeds greater cravings. Ask Philadelphians about their cheesesteaks, New Orleans denizens about their Po-Boys and beignets, or Memphians about their barbecue. Surprise! Those are among the three most obese cities in the country. Coincidence?

      As prodigious as some American cuisine is, is there really anything special about a soda, a French fry, or any item in a fast food restaurant? Yet we devour fast food as if it were going out of style. Americans consume Big Macs as if each one might be our last. (Given the mortality rates in the obese, each one just might be.) Fast food comprises a growing portion of food eaten outside СКАЧАТЬ