 Dr. Lustig is a neuroendocrinologist, with basic and clinical training relative to hypothalamic development, anatomy, and function. Prior to coming to San Francisco in 2001, he worked at St. Jude Children's Research Hospital in Memphis, TN. There, he was charged with the endocrine care of many children whose hypothalami had been damaged by brain tumors, or subsequent surgery, radiation, or chemotherapy. Many patients who survived became massively obese. Dr. Lustig theorized that hypothalamic damage led to the inability to sense the hormone leptin, which in turn, led to the starvation response. Since repairing the hypothalamus was not an option, he looked downstream, and noted that these patients had increased activity of the vagus nerve (a manifestation of starvation) which increased insulin secretion. By administering the insulin suppressive agent octreotide, he was able to get them to lose weight; but more remarkably, they started to exercise spontaneously. He then demonstrated the same phenomenon in obese adults without CNS lesions. The universality of these findings has enabled Dr. Lustig to weave these threads together into a novel unifying hypothesis regarding the etiology, prevention, and treatment of the current obesity epidemic. This has led him to explore the specific role of fructose (half of sucrose and high-fructose corn syrup) as a specific mediator of both chronic disease, and continued caloric consumption. His now notorious YouTube video, "Sugar: The Bitter Truth," continues its popularity with the lay public. |
| Abstract: The prevalence of obesity continues to climb in all age groups, and around the world. The standard paradigm assumes that we “eat too much and exercise too little, that obesity is due to two aberrant “behaviors”. However, are these behaviors cause or effect? Our research on children with brain tumors who develop hypothalamic damage and become obese after surgery or radiation, termed “hypothalamic obesity”, demonstrates that they have anatomic “leptin resistance”. In these subjects, excessive insulin release blocks leptin signaling to drive weight gain and hunger, while pharmacologic insulin suppression results in reduced food intake, increases spontaneous activity, and promotes weight loss. Why should insulin block leptin signaling? Leptin is a necessary signal to the VMH for the initiation of high-energy processes, such as puberty and pregnancy. If leptin always worked, then nobody could gain weight, and our reproductive capacity would be shot. Most obese people are hyperinsulinemic. But is that cause or effect? It is assumed that as you gain weight, cytokines are released from adipose tissue, which drive insulin resistance. However, our research demonstrates that dietary sugar is metabolized to fat in the liver, and it is this liver fat that drives insulin resistance unrelated to peripheral fat. Why should sugar drive insulin resistance? Naturally occurring sugar in fruit is what makes fruit palatable. But for our ancestors, fruit was readily available for one month per year, called “harvest time”. Then came four months of winter, and no food at all. We needed to stock up, to increase our adiposity in preparation for four months of famine. In other words, seasonal insulin resistance was evolutionarily adaptive; but year-round insulin resistance due to ubiquitous sugar availability has become maladaptive. It is assumed that people consume sugar because of its palatability. However, there is now evidence that sugar may be addictive in humans. Obese subjects will use sugar to treat psychological symptoms. Overweight women who were self-reported carbohydrate cravers reported greater relief from dysphoria in response to a carbohydrate-containing beverage as compared to a protein drink. Why are we drawn to sweet? Evolutionarily, sweetness was the signal to our ancestors that a given food was safe to eat because there are no sweet foods that are acutely poisonous (even Jamaican vomiting sickness only occurs after consumption of unripe ackee fruit, which is not sweet). Unfortunately, the food industry knows this and adds excess sugar to processed food to make us buy more. Thus, the behaviors associated with obesity are secondary to our biochemistry, and our biochemistry is secondary to our environment. Understanding these evolutionary precepts explain our obesity epidemic, and also point to environmental and policy solutions. |