Posts Tagged ‘brain’

Are Persons with Obesity Different?

September 27th, 2011

Are persons with obesity different? The question is fraught with implications. Much of obesity policy is premised on the assumption that persons with obesity are just like normal weight persons but with less self-control. The assumption is that education and awareness will overcome their lack of awareness and result in more self-control, just like normal weight persons. Of course, a genetic basis for obesity is counter to this assumption. How does this genetic pre-disposition express itself? Two recent studies may provide insights. In one, overweight persons show a higher capacity for storing fats but a lower capacity for ridding themselves of them, using the radioactive isotope carbon-14. Cell dysfunction linked to obesity and metabolic disorders | ScienceBlog.com

 In another study, the brains of persons with obesity were found to create a greater desire for high-calorie foods than normal-weight subjects which would explain why people who become overweight tend to remain overweight. Study: Obese people’s brains may crave high-calorie foods – USATODAY.com

Brain affected in obese adolescents with type 2 diabetes

June 23rd, 2011

Adults with type 2 diabetes have reduced hippocampal and frontal lobe volumes in the brain. A new study looked at obese adolescents with type 2 diabetes compared to obese adolescents without type 2 diabetes and found significantly reduced hippocampal and prefrontal volumes and higher rates of global cerebral atrophy and HbA1c. This indicates that brain integrity it negatively impacted by type 2 diabetes long before the onset of overt macrovascular disease. The authors called for more aggressive treatment of obesity and diabetes in children and adolescents Obese Adolescents with Type 2 Diabetes Mellitus Ha… [Neurosci Med. 2011] – PubMed result

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

Understanding Obesity

September 26th, 2009

While body weight is made up of several components – bone, muscle, etc. when we talk about obesity we are referring to excess fat tissue, also called adipose tissue. There are two kinds of fat tissue, brown and white (like rice come to think of it). Brown tissue is mainly found in newborn babies which serves to protect babies by releasing heat. It is converted into white cells in adults. (Scientists are looking at whether white can be converted back into brown tissue and burnt off.) White adipose tissue is made up of cells called adipocytes. These contain fat made of triglycerides and other compounds. White fat cells secrete resistin, adiponectin and leptin. The average adult has 30 billion fat cells weighting about 30 pounds. Fat cells can increase in size about 4 fold before dividing and increasing the total number of fat cells present. Adipocytes also secrete estrogen which probably accounts for higher rates of some cancers in obese persons. Adipose tissue also secrete cytokines. Among the most interesting cytokines identified has been leptin, a molecule considered to send signals to the brain of satiety, i.e. the signal to the brain to stop eating.

Genetic Basis of Obesity

September 26th, 2009

Often one hears it stated that obesity is not a genetic disease. If by that the speaker is saying that obesity is probably not due to a single genetic change they are not quite right. There are some rare forms of obesity which are due to a single gene change. Genetic obesity syndromes. [Front Horm Res. 2008] – PubMed Result; Genetic and hereditary aspects of childhood obesit…[Best Pract Res Clin Endocrinol Metab. 2005] – PubMed Result But if they mean a single genetic change cannot account for a worldwide epidemic of obesity occurring over the last 30 years they are probably right. If the speaker means it is unlikely that there will be a treatment for obesity based on gene therapy, they are probably correct. (Although who can predict the future?) However, they miss the point if they do not understand that for millions of years of evolution, the species we call humans have favored genes which maximize its chances for survival and reproduction. So our taste preferences, our physical activity preferences and the like are passed on in the genome and our part of our inheritance. The problem is that for centuries we humans lived in an environment which was totally different than the one we live in now. The disconnect is that our bodies have not yet adapted to this new world where tasty, nutritious food is readily available and where most of us do not have to expend anything other than a minimal effort to obtain it, survive and flourish. Anything policy-makers or parents want to do about obesity must be understood in the context of the powerful force evolution has been in designing how humans acquire, store and use energy from food.

According the CDC:

  1. Biological relatives tend to resemble each other in many ways, including body weight. Individuals with a family history of obesity may be predisposed to gain weight.
  2. Different responses to the food environment are largely due to genetic variation between individuals.
  3. Fat stores are regulated over long periods of time by complex systems that involve input and feedback from fat tissue, the brain and endocrine glands like the pancreas and the thyroid. http://www.cdc.gov/genomics/training/perspectives/files/obesknow.htm,
  4. The tendencies to overeat and be sedentary, the diminished ability to use dietary fat as fuel and enlarged, easily stimulated capacity to store body fat are all genetically influenced. The variation in how individuals respond to the food rich environment and the differences in acquiring obesity related comorbid conditions are also genetically determined. http://www.cdc.gov/Features/Obesity/

Since 1997, published studies have found that variation in BMI is largely due to heritable genetic differences, with estimates ranging from 55% to 85%. A 2008 study found that 77% of the adiposity in preadolescent children born since the start of the obesity epidemic was due to genetic inheritance compared to 10% for the environment. Evidence for a strong genetic influence on childho…[Am J Clin Nutr. 2008] – PubMed Result

A fast rate of eating appears to be heritable. Eating rate is a heritable phenotype related to we…[Am J Clin Nutr. 2008] – PubMed Result Differences in responding to the obesogenic environment may also be heritable Genetic influence on appetite in children. [Int J Obes (Lond). 2008] – PubMed Result and Appetite is a Heritable Phenotype Associated with …[Ann Behav Med. 2009] – PubMed Result. The FTO gene may be involved. The FTO gene and measured food intake in children. [Int J Obes (Lond). 2009] – PubMed Result and Increasing heritability of BMI and stronger associ…[Obesity (Silver Spring). 2008] – PubMed Result Parental leanness appears to provide strong protection against the development of obesity in children. Development of overweight in children in relation …[Obesity (Silver Spring). 2009] – PubMed Result

There is an interesting scientific debate about what is called the “thrifty gene” hypothesis about how a genetic preference for storing extra energy on our bodies might have developed. Thrifty genes for obesity, an attractive but flawe…[Int J Obes (Lond). 2008] – PubMed Result and The clinical biochemistry of obesity. [Clin Biochem Rev. 2004] – PubMed Result. Some think that childhood obesity is increasing due to ‘associative mating’ by overweight parents who pass on their genetic disposition to obesity to their children. Childhood obesity: are genetic differences involve…[Am J Clin Nutr. 2009] – PubMed Result

The evidence for the genetic basis of obesity, in addition to environmental changes is quite strong. See Implications of gene-behavior interactions: preven…[Obesity (Silver Spring). 2008] – PubMed Result; Genome-wide association scan shows genetic variant…[PLoS Genet. 2007] – PubMed Result and The genetics of obesity. [Metabolism. 1995] – PubMed Result

The environment is thought to be responsible for variations between populations but genetics is responsible for the variations within a given population. Obesity – Missing Heritability and GWAS Utility and Genetic and environmental factors in relative body…[Behav Genet. 1997] – PubMed Result. Genetics may account for many cases of morbid obesityFamilial aggregation of morbid obesity. [Obes Res. 1993] – PubMed Result.

Genetics may play an important role in determining who can benefit from different types of intervention. Implications of gene-behavior interactions: preven…[Obesity (Silver Spring). 2008] – PubMed Result or who is more likely to be affected by obesity Ethnic variability in adiposity and cardiovascular…[Int J Epidemiol. 2009] – PubMed Result. Or experience a comorbid condition like Type 2 diabetes Mechanisms of disease: genetic insights into the e…[Nat Clin Pract Endocrinol Metab. 2008] – PubMed Result

The FTO gene is currently under active research interest for providing a link to how obesity related conditions might arise and how patients can benefit from this knowledge. FTO: the first gene contributing to common forms o…[Obes Rev. 2008] – PubMed Result Genome-wide association scan shows genetic variant…[PLoS Genet. 2007] – PubMed Result

The FTO gene may explain different responses to exercise. FTO Genotype Is Associated With Exercise Training-…[Obesity (Silver Spring). 2009] – PubMed Result .Physical activity and the association of common FT…[Arch Intern Med. 2008] – PubMed Result

A factor in the resistance to describe obesity as a genetic disease may be in the assumption that the human genome does not change rapidly whereas the increase globally in the rates of obesity have occurred in the last 40-50 years. However, evolutionary biologists are debating the speed of genetic change. In “Catching Fire, How Cooking Made us Human” (Basic Books, New York, 2009) Richard Wrangham, the Ruth Moore Professor of Biological Anthropology at Harvard University writes,

A long delay between the adoption of a major new diet and resulting changes in anatomy is also unlikely. Studies of Galapagos finches by Peter and Rosemary Grant showed that during a year when finches experiences an intense food shortage caused by an extended drought, the birds that were best able to eat large and hard seeds – those birds with the largest beaks- survived best. The selection pressure against small-beaked birds was so intense that only 15 percent of birds survived and the species as a whole developed measurably larger beaks within a year. Correlations in beak size between parents and offspring showed that the changes were inherited. Beak size fell again after the food supply returned to normal, but it took about fifteen years for the genetic changes the drought had imposed to reverse. The Grants’ finches show that anatomy can evolve very quickly in response to dietary changes…Other data show that if an ecological change is permanent, the species also changes permanently, and again the transition is fast…The adaptive changes brought on by the adoption of cooking would surely have been rapid. (p. 93-94, emphasis added.) (See Book Reviews)

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