Disclosures Introduction Clinicians know that excess body fat increases cancer risk and are often frustrated by the failure of their overweight/obese patients to follow weight control advice. Patients are equally disappointed when they can't reach their weight loss goals. Many patients become so anxious that they fast for several days before an office visit and have to “face the scale”. Any weight loss from this is almost always quickly regained, or even more, and the frustration continues. The fat problem is getting worse, especially in children and adolescents. In some countries over 50% of adults are obese. . This article examines some clinical weight control “pearls” I have found helpful, along with recent research linking cancer to products made by fat cells (adipokines). This is a good example of basic science informing patient care. Lessons learned in the clinic People like to eat and must have a clear understanding about the reasons for weight control. It helps to point out that fat cells makes at least one cancer-stimulating chemical (leptin), and that being overweight/obese is associated with increased risk of dying from most common cancers, including cancer of the breast, prostate, colon and rectum, pancreas and ovary . Too much fat is also a risk factor for Alzheimer's disease; most patients don't know this, and it gets their attention. The extra weight did not appear overnight and will not disappear overnight either, so suggest starting slowly, perhaps with a 3-day diet diary to see what food types should be cut back. The patient can begin by reducing one offending food like too much red meat, and start to substitute; add a vegetable for fried potatoes, for example. There is no magic food, pill or diet. One can suggest beginning mild exercise (20 minutes of walking daily to start, perhaps with a friend for mutual encouragement); breaking a sweat, but no power walking. Leisure-time physical activity reduces risk of 13 kinds of cancer, including lung, esophageal, liver, bladder and breast . It does not have to be painful to start losing weight, it does not require a fancy machine or diet pills, and one does not have to lose all their excess body fat to decrease disease risk. Though there is limited data on the degree of weight loss and cancer risk , work towards an achievable target, such as about 5% of current weight (10 pounds in a 200-pound person, for example). I know that a busy physician needs help with this. A good dietitian can do initial planning and follow up and designation of a team member, a nurse or PA for example, as the office nutrition resource can improve compliance through office visits and phone calls. Both can educate patients about fat and adipokines. Adipokines A new area of clinically important research looks at how fat does its harmful work. Fat is not just a storage facility for excess calories but acts like a gland, making hundreds of biologically active chemicals called adipokines. Most of these are poorly understood, but two, leptin and adiponectin, are closely associated with cancer . There is evidence that leptin increases cancer risk  and adiponectin decreases cancer risk . A short explanation of these adipokines helps patients understand the importance of weight control on a practical level. Leptin and adiponectin are also involved in the clinical observation that cancer and Alzheimer's disease tend to inhibit one another . Patients find this very interesting. Leptin Leptin is a curious fat cell product that has normal and abnormal cellular and molecular activities. It normally regulates appetite. As body fat increases, leptin levels rise and appetite decreases, but this mechanism can fail (“leptin resistance”). Then leptin and body fat continue to increase, leading to higher risk for cancer and other serious chronic diseases . The mnemonic “He got fat and cancer lept in” helps patients remember. Adiponectin Adiponectin is normally involved in glucose control, has anti-inflammatory actions and can inhibit cancer. There is an inverse relationship between adiponectin and several major cancers including cancer of the breast, colon, prostate, and pancreas. Normally, leptin levels fall and adiponectin levels rise with weight loss, both of which can decrease cancer risk [8,9]. Mechanisms: 'prone to live' and 'prone to die' How do leptin and adiponecin influence cancer at the cellular and molecular level? These relationships are complex, and involve competing actions on apoptosis (programed cell death), angiogenesis (new blood vessel generation), and the important cell signaling factors p53, Wnt, and Notch. Leptin inhibits apoptosis, allowing damaged (cancer) cells to live, while adiponectin can promote apoptosis to remove damaged cells. This has been called the “prone to live” or cancer state (leptin) versus the “prone to die” or anti-cancer state (adiponectin) . Similarly, leptin can stimulate angiogenesis to feed newly formed tumor cells (“prone to live”) while adiponectin can starve cancer by inhibiting angiogenesis (“prone to die”). At the molecular level, both adipokines affect p53 and Wnt, and leptin affects Notch. P53 is a gene /gene product that acts as a tumor suppressor. Leptin downregulates p53 in a cell-proliferative, anti-apoptotic “prone to live” direction , while adiponectin stimulates p53 to promote growth arrest and apoptosis (“prone to die”) . Wnt is a gene family involved in normal and abnormal cell signaling. Leptin can stimulate Wnt to increase cell proliferation (“prone to live”), while adiponectin can counteract this by decreasing Wnt [8,9]. Notch is involved in the development of blood vessels and the breast, gut, and nervous system . Leptin upregulates Notch, increasing activity of growth factors and stimulating cell proliferation (“prone to live”). Not much is known about adiponectin and Notch [8,9]. Conclusions Patients will not heed weight control advice if they do not understand why it is so important. They need to know that (contrary to some of the severe diet and exercise regimens in the popular literature and on TV), it is not necessary to suffer to lose weight. They can start slowly with small dietary changes and mild exercise. They do not need to try to lose all their fat or to get back to their youthful weight (which is not going to happen anyway), but with proper dietary changes they do not have to be hungry. It is important to explain how fat stimulates cancer, and that weight loss helps reduce this; the health care team and the patient can effectively partner in this effort, with the team encouraging the patient and setting examples where possible. Obesity is increasing worldwide, and fat-related chronic diseases, including cancer and Alzheimer's disease, threaten to overwhelm an already stressed healthcare system. More public health research on the causes and prevention of the obesity epidemic and the health effects of excess body fat is clearly needed. The best body weight for good health in children and adults is not clear, but excessive dieting and extreme weight loss is a bad idea. A single practice can't do much about the larger public health problem, but weight control begins at home. Success in one patient helps and may extend to the patient's family and friends in a widening circle. The individual practice can make a difference, and many practices can make a big difference; just look at the decline in deaths from cardiovascular disease in the UK and US .