Posts Tagged ‘insulin’

Cancer and Obesity Explored

November 3rd, 2011

The Institute of Medicine’s National Cancer Policy Forum this week convened a two-day workshop, “The Role of Obesity in Cancer Survival and Recurrance.” So this is a good opportunity to re-visit the relationship between these two deadly diseases. Susan Gapstur of the American Cancer Society noted the growing list of cancers associated with obesity. For men, these include cancers of the colon, esophagus, kidney, colorectum, pancreas, gallbladder and liver. Women are affected by the same cancers as well as of the endometrium and postmenopausal breast cancer. Evidence is accumulating for an association with non-Hodgkin’s lymphoma, ovarian cancer in women and aggressive prostate in men. Obesity, she pointed out, is not the second (to tobacco) leading risk factor of cancer. Ominously, she pointed out we do not know what the health effects will be for the children now obesity who will obese for a lifetime.

Pamela J. Goodwin of the University of Toronto explored potential mechanisms in the progression to cancer including inflammation, adipokines, hyperinsulinemia, diabetes/diabetes drugs and sex steroids. She pointed to studies showing reductions in cancer risk with intentional weight loss of 20 pounds or more. Intentional weight loss and in… [Int J Obes Relat Metab Disord. 2003] – PubMed – NCBI and reduction in the relative risks of death and of cancer following bariatric surgery. Metabolic surgery and cancer: protective effects of b… [Cancer. 2011] – PubMed – NCBI.  Specifically, she showed the positive effect of intentional weight loss on breast cancer risk   Does intentional weight loss reduce canc… [Diabetes Obes Metab. 2011] – PubMed – NCBI and the impact of physical activity on improvements in insulin in breast cancer survivors Impact of a mixed strength and endurance exerci… [J Clin Oncol. 2008] – PubMed – NCBI.

Bruce Wolfe of the Oregon and Science University and a bariatric surgeon reminded the participants that the Swedish Obesity Study found the reduction in mortality after bariatric surgery was greater for cancer than for cardiovascular events Effects of bariatric surgery on mortality in Sw… [N Engl J Med. 2007] – PubMed – NCBI. In a Utah study, bariatric surgery reduced deaths from cancer by 60% compared to a 48% reduction in cardiovascular events. Long-term mortality after gastric bypass surgery. [N Engl J Med. 2007] – PubMed – NCBI

Rachel Ballard-Barbash of the National Cancer Institute, who has been a leader in exploring the obesity-cancer connection for many years, moved the discussion to look at the co-morbid conditions of obesity and their relationship to cancer mortality, including renal disease, congestive heart failure, cerebrovascular disease, citing A refined comorbidity measurement algorithm fo… [Ann Epidemiol. 2007] – PubMed – NCBI

Patricia Ganz of the UCLA Schools of Medicine picked up the point and explained that about half of all deaths of breast cancer survivors are due to causes other than breast cancer. She recommended prevention of weight gain and/or weight loss in those breast cancer survivors who are obese. 

Thomas Wadden described the non-surgical approaches to weight loss used in the Diabetes Prevention Program and the LOOK Ahead study and the contribution of intensive behavioral counseling to reduction in comorbid conditions associated with obesity

Some of the workshop’s presentations are on-line at Workshop on the Role of Obesity in Cancer Survival and Recurrence – Institute of Medicine. Watch that site for future information on a publication from the workshop.

Why the weight lost comes back

October 28th, 2011

It comes as no surprise that regaining weight after weight loss is common and frustrating to dieters. It also limits choices for policy makers who, in general, had avoided treatment strategies because of the transient nature of weight loss.

It also comes as no surprise that, after weight loss, metabolism of overweight persons slowed down and hormonal changes increased the powerful sensation of hunger. This double whammy makes maintenance of weight loss so challenging.

Now come researchers from Australia who studies a small group (only 50 overweight and obese patients without diabetes) . The group lost about 13.5kg  which led to reductions in levels of leptin, peptide YY, cholesystokinin, insulin and amylin and increases in ghrelin. There was also an increase in subjective appetite.(See Brain and Gut for background.) What is new is that these changes persisted for one year after initial weight loss. They did not revert to the levels recorded before weight loss, probably explaining why so many dieters relapse. See http://www.ncbi.nlm.nih.gov/pubmed/22029981.

Gina Kolata, writing in the New York Times, quotes Dr. Jules Hirsch as saying that researchers may just not know enough about obesity to prescribe solutions yet. “One thing is clear, he said, “A vast effort to persuade the public to change its habits just hasn’t prevented or cured obesity.” “We need more knowledge,” Dr. Hirsch said, “Condemning the public for their uncontrollable hedonism and the food industry for its inequities just doesn’t seem to be turning the tide.” Study Shows Why It’s Hard to Keep Weight Off – NYTimes.com

Downey Fact Sheet 1 – About Obesity

September 27th, 2009

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Obesity is a global epidemic and a major health concern because of its premature mortality and extensive comorbidities. Obesity is a common, complex, multifactorial disease with a high degree of heritability. Between 25 and 40% of person with obesity have a parent who is obese. There are several significant facts to bear in mind when discussing obesity:

By Julie Snider for the Downey Obesity Report

By Julie Snider for the Downey Obesity Report

Every individual inherits a certain number of fat cells or adipose tissue. Obesity requires (a) a large number of fat cells or (b) a large volume in each fat cell or (c) both. Adipose tissue continues throughout the lifespan. Weight loss, including surgically-induced weight loss, does not remove fat cells. This is why weight regain is so common. Individuals with obesity have significantly more fat cells than the non-obese, 23-65 billion compared to 37-237 billion for persons with obesity . Early onset obesity is associated with increase adipose cell number while adult obesity is associated with normal cell number. There are two phases of life in which growth of adipose cells are likely to develop: very early, within the first few years of life and between the ages of 9-13 years of age. Those who become very obese early in life are the ones who have nearly normal cell size but have the greatest increase in cell number; whereas those with onset of obesity between 9-13 have more change in cell size than cell number. Salans LB, Cushman SW, Weisman RE, Studies of human adipose tissue. Adipose cell size and number in non0bese and obese patients. J. Clin Invest. 1973 Apr’ 52(4): 929-41)

Extremely obese individuals may have four times the number of fat cells as lean counterparts. http://www.jpp.krakow.pl/journal/archive/1205_s6/pdf/5_1205_s6_article.pdf

Human food intake and energy expenditure are controlled by complex, redundant and distributed neural systems that reflect fundamental biological reaction to food supply and energy balance. The hypothalamus and caudal brainstem play a critical role. The limbic system is important for processing information regarding previous experience with food, reward and emotion. The predisposition to store considerable amounts of energy as fat for later use is now a major health risk. Brain, appetite and obesity – PubMed Results

Extensive research over the past 10 years has shown that appetite is regulated by a complex system of central and peripheral signals which interact in order to modulate the individual response to nutrient ingestion. Satiety signals include cholecystokinin, glucagon-like peptide and peptide YY which originate from the gastrointestinal tract during a meal and through the vagus nerve reach the caudal brainstem. Here the signals move to the arcuate nucleus where satiety signals are integrated with adiposity signals, namely leptin and insulin, and with several other inputs create a neural circuit which controls the individual’s response to a meal, i.e. keep eating or stop. Neuro-hormonal control of food intake: basic mecha…[J Physiol Pharmacol. 2005] – PubMed Result

Adipose tissue, rather than some inert, jello-like, substance is an active hormonal tissue, secreting many hormones which are involved in creating signals from the gut to the brain, indicating hunger or satiety. These hormones include insulin, leptin, ghrelin, PYY-33-6, adiponctin, resistin and visfatin as well as cytokines and chemokines, such as tumor necrosis factor-alpha, interleukin-6 and others. These can lead to a chronic sub-inflammatory state which plays a critical role in the development of insulin resistance, type 2 diabetes, increased risk of cardiovascular disease associated with obesity. Adipokines: the missing link between insulin resis…[Diabetes Metab. 2008] – PubMed Result

Brain and Gut

September 26th, 2009

Frequently, when persons with obesity are depicted in the media, they are headless forms (butts and guts I call the pictures) for we think of obesity in terms of body fat accumulation. But obesity really starts in the brain with multiple signals coming from the gut. Adipose tissue itself generates hormones such as leptin and adiponectin; the GI tract generates ghrelin which signals the brain to initiate feeding . Other products which may stimulate feeding or signal time to stop feeding include leptin, insulin neuropeptide Y among others. Parts of the brain involved are the hypothalamus, the dorsal vagal complex and the reward system.

Researchers now appreciate that food acquisition, preparation, and intake are the result of a several physical signals by which the body communicates to the brain that it is hungry and needs to start feeding or full and needs to stop. MD

Brain

So, just how does the body regulate its weight? The body needs to get its weight just right. Too little nourishment and the body becomes ill and cannot reproduce. Too much also a problem. Look at the precision needed. If one ate the recommended 2,200 calories per day (and a lot eat a lot more) they would consumer 792,000 calories in a year. If they are just 1% more calories, they would add 2 pounds per year or 20 pounds over a decade of life. That’s just an extra 22 calories a day – about half a lower fat Oreo cookie. 100 extra calories a day – about 2/3 of 1 ounce of potato chips – can result in a 5-pound weight gain a year. To keep within these narrow boundaries of health body weight, our bodies have evolved a sophisticated, redundant system to gauge its body weight and when to feed and when to stop feeding.

The four parts of this system are (1) the nervous system which connects the brain, gut and adipose tissue, (2) hormones, including those made by fat cells, (3) neuropeptides which act as messengers and (4) messenger molecules in the immune system called cytokines. These molecules control body weight. The pancreas and adipose tissue make leptin, insulin, adiponectin, visfatin and resistin. The brain makes NPY, melanocortin and cocaine and amphetamine regulated transcript called CART. The stomach makes ghrelin, PYY and CCK.

The process can begin before you eat. Even the sight, smell or thought of food can trigger the “cephalic response.” This can start the production of insulin. Ghrelin increases the desire to eat. PYY can signal an end to feeding. Under stress, the sympathetic nervous system is activiated. This promotes storage of fat, decreases metabolism and promotes insulin resistance. Weight increases and metabolism slows down when this system is activated. The key hormone is insulin which is produced in the pancreas. It is designed to use carbohydrates or store them for later use.

The signals to the brain come from both the central nervous system and the peripheral nervous system Central and peripheral regulation of food intake a…[Obesity (Silver Spring). 2008] – PubMed Result

They appear to converge in the hypothalamus region of the brain.Hypothalamic control of energy balance. [Curr Drug Targets. 2004] – PubMed Result

No fewer than ten possible automatic and largely uncontrollable responses to the modern food environment have been proposed to understand why people can consume more calories than they need without their full awareness or control over their behavior Neurophysiological pathways to obesity: below awar…[Diabetes. 2008] – PubMed Result

Obese individuals appear to respond differently to food visual cues Obese adults have visual attention bias for food c…[Int J Obes (Lond). 2009] – PubMed Result

Obese and overweight persons appear to have lower brain volume Brain structure and obesity. [Hum Brain Mapp. 2009] – PubMed Result

Gut Hormones

Leptin has been identified as one of the most powerful hormones involved in appetite regulation. Appetite control and energy balance regulation in …[Int J Obes (Lond). 2009] – PubMed Result Now, newer techniques like brain imaging can be used to understand the role the brain and central nervous system play in eating behaviours.Leptin regulates striatal regions and human eating…[Science. 2007] – PubMed Result and Neuroimaging and obesity: mapping the brain respon…[Ann N Y Acad Sci. 2002] – PubMed Result

Another class of signaling substances are neuropeptides. Orexin is one of several currently of interest to scientists. Orexin/Hypocretin: a neuropeptide at the interface…[Pharmacol Rev. 2009] – PubMed Result and Orexin neuronal circuitry: role in the regulation …[Front Neuroendocrinol. 2008] – PubMed Result

Chronic stress and obesity: a new view of “comfort…[Proc Natl Acad Sci U S A. 2003] – PubMed Result

Maternal corticotropin-releasing hormone levels du…[Obesity (Silver Spring). 2006] – PubMed Result

The role of gut hormones in the regulation of body…[Mol Cell Endocrinol. 2009] – PubMed Result

Gut hormones: a weight off your mind. [J Neuroendocrinol. 2008] – PubMed Result

Gut hormones and appetite control. [Gastroenterology. 2007] – PubMed Result

Cord blood leptin and adiponectin as predictors of…[Pediatrics. 2009] – PubMed Result

The leptin/adiponectin ratio in mid-infancy correl…[J Pediatr Endocrinol Metab. 2008] – PubMed Result

As research progresses, new theories of evolutionary development are looking at Build-ups in the supply chain of the brain: on the…[Front Neuroenergetics. 2009] – PubMed Result

Ghrelin is a gut hormone which appears to be very significant and is the subject of much research.Lean Mean Fat Reducing “Ghrelin” Machine: Hypothal…[Neuropharmacology. 2009] – PubMed Result

Appetite

Viewing photographs of fattening foods, compared to non-food objects can result in greater activiation in parts of the brain. Activation in brain energy regulation and reward c…[Int J Obes (Lond). 2009] – PubMed Result In one study, obese women had greater brain activity in response to pictures of high fat foods than did non-obese women. Widespread reward-system activation in obese women…[Neuroimage. 2008] – PubMed Result and Effective connectivity of a reward network in obes…[Brain Res Bull. 2009] – PubMed Result

Gut peptides and the regulation of appetite. [Obes Rev. 2006] – PubMed Result