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Overview
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Active Learning Projects - Obesity Project - Team 5    
 
Obesity
Team 1   Team 2   Team 3   Team 4   Team 5   Instructions du Projet
 
1. Regulation of food intake and obesity
2. Messengers involved in the homeostatic regulation of food intake
3. Messengers involved in the hedonic regulation of food intake
4. Signalling mechanisms in the arcuate nucleus and the regulation of food intake
5. Treatment of obesity
Instructions du Projet

active learning, any time, any place and anywhere

Homer-donut

5. Treatment of obesity

Summary:
Introduction
Medicaments
Bariatric surgery

Auteurs:
Aurore Brun, Rémie Eliautout, Johara Nadri, Fanny Soulié.

Introduction

reddot Weight loss of obese people of as little as 5-10% is associated with an improved quality of life (fewer cardiovascular accidents, less diabetes and others) and with a reduction in mortality rates. While it is estimated that, over the long term, small adjustments in daily food intake, in the order of a reduction of 50 kcal per day (one slice of bread less each day), should reduce body weight, analysis of clinical data in the United Kingdom suggests that meaningful weight loss of the obese, in the order of 5 kg in a year, can only be achieved through adherence to a 600 kcal energy-deficit diet. This amounts to skipping almost one meal a day. Unfortunately, such diet restriction often has substantial negative psychological consequences (a lack of reward signals) and compliancy is generally low (see figure 1). Indeed, whereas non-pharmacological methods of obesity therapy demonstrate short-term efficacy (a loss of a number of kilograms in a couple of months), about half of that weight-loss is regained within one year and all the weight is regained within five years.

reddot Rather than reducing food intake, one could also increase physical activity with an additional 600 kcal per day. For instance, 60 minutes cycling at 200 watts should do the job. But for most of us, this is hell. In conclusion, for a large majority, meaningful weight reduction requires a little help, either from a medicament (a really effective one is not yet on the market), an adorable (and expensive) personal coach (whose intimate presence makes up for the lack of food rewards) or a bariatric surgeon. Below we discuss medicaments and bariatric surgery.

Figure 1 The hardship of changing eating habits shows on the face of Homer Simpson.

Changing lifestyle
As mentioned by team 1, it is not clear what causes the obesity pandemic. Nevertheless, the finger is pointed to the general obesogenic lifestyle that reigns in “high-income” countries. Changing life style therefore seems the most appropriate remedy. In light of this, numerous health organizations have published life-style guidelines. These can be summarized as: eat less, eat better and exercise more. French slogans are:
“depenses-toi bien” and “manger mieux et bouger plus” (http://www.mangerbouger.fr)
English slogans are:
“eat well”, “move more” and “live longer” (http://www.nhs.uk/change4life/Pages/change-for-life.aspx)

The French health ministry provides nine essential points for a healthy and balanced diet

  1. fruits and vegetables; five times per day and with variety
  2. milk products; three time per day
  3. starch (amidon); each meal
  4. meat, fish or eggs; once or twice per day
  5. fat; limited and choose for the good source (mono- or poly-unsaturated)
  6. sugar; with moderation
  7. salt; with moderation
  8. water; feel not restricted
    and importantly,
  9. pay attention to your meal, eat with pleasure. Do not turn eating into a secondary activity, next to watching television or reading blogs on your computer.
Thirty (30) minutes physical activity per day
The importance is to “spend energy”. A logical, as well as environmental friendly, approach would be to walk or to cycle for the short distances where people normally take their cars or a bus/tram. For instance the daily trip to work, local shopping or going to the movies. Not only would this free urban areas from the terror of the car, and allow us to use public space for a variety of activities, it would also help to maintain a reasonable body weight (see also “the daily commute” below). To these activities one can add sport sessions.

Physical activity is particularly important during youth as it has an important impact on the development of the cardiovascular system. A good cardiovascular system makes spending energy all the more easier because it allows one to burn more body fat per minute. An athlete spends much more energy in one hour running than untrained people, even although he/she does not appear to suffer as much (see table 1 below and compare walking at 4 or 5 km/hr). The worse the state of the cardiovascular system, the more time it will take to burn a good deal of body fat (endless jogging, swimming, cycling or stepping), the more one gets frustrated about the effort it takes to lose weight, the quicker one gives up; a vicious circle.

Activity speed (km/hr) energy consumption (kJ/min)
Sitting on a chair (in train or bus)   1.5
Standing, relaxed   2.6
Standing, restless (in crowded metro)   6.7
Walking on even path 4 14.1
Walking on even path 5 18.0
Cycling on even path 12 14.7
Driving a car on clear roads   4.2
Driving a car, in city, rush hour   13.4

Table 1 (a) Measured average values of corporal-energy consumption per unit time for different activities (ranging from sitting on a chair to walking)

The daily commute
Straightforward as it may seem, the “move more” slogan of health institutions will face a tremendous resistance when it comes to changing the daily commute. It is estimated that people spend on average 147 Kcal (615 kJ) per day during their travel to work, be it by train, bus, car, bicycle or foot. What followed from an analysis of commuter habits, if the effort is little, meaning little corporal-energy consumption per minute, the travel is allowed to be long, if it is hard, the travel necessarily must be short. See table 1 for the corporal-energy consumption rates for different modes of transport. (NB do not confuse with the energy consumption of the train, the bus or the car, that is a different story).

From this analysis two important lessons can be learned: firstly, people shy efforts in their daily routine, 147 kcal is peanuts compared to the amount of food we (can) eat; secondly, even if health guidelines manage to chase people out of their car and make them commute otherwise, the newly adopted modes of transport are unlikely to exceed the 147 Kcal per day. Commuters will find new modes transport, assuring a low corporal-energy bill per journey, or they will reduce the distance between work and living. Apparently, perturbing the 147 Kcal “homeostasis” (the drive of organisms to maintain a stable, constant condition) is a real challenge.

Moreover, and surprisingly, from table 1 it follows that, with respect to weight control, driving a car during rush hour renders nearly as slim as walking at 4 km/hr or cycling at 12 km/hr*. In short, not only do people have to walk or cycle, they also would have to walk or cycle fast. Alternatively they move slowly but for a longer period of time than their daily commute by car! This, for the majority of people, would seem absurd.

*It may, however, not have the same impact on our cardiovascular system as indicated in a study by Morris et al. in 1953, which showed that bus drivers, who sit, have more heart trouble than bus conductors, who, in those days, walked around in their double-decker (the old RT-type buses, predecessor of the famous Routemaster).

Information sources:

  1. Kolbl R, Helbing D. Energy laws in human travel behaviour New Journal of Physics 2003;5:48.1-48.12
  2. Morris JN, Heady JA, Raffle PA, Roberts CG, Parks JW (). "Coronary heart-disease and physical activity of work". Lancet 1953;265(6795):1053-7
Does bad food exist?
Imagine you are overweight and you have bought, in a weak moment of self-control, a couple of Mcdonald hamburgers and Mars bars. You haven’t yet touched them as the good part of you has regained control after the purchase. They lay on the rear seat of your air-conditioned vehicle. You happen to travel through a drought- and war-ridden country and come across someone who shows clear signs of starvation. Because of your regain of self-control, you are in a charitable mood and stop. Logically, the person begs you for food and drink. You search your vehicle and, after some hesitation, apologize that, apart from water, you have nothing to offer. The starving person gratefully acknowledges the water but, because he/she has seen a glimpse of the hamburgers and the Mars bars, insists to share some of the food as well. You shyly apologize for being in possession of such bad things, but, in turn, insist that you cannot share it because it would make you an accomplice of the bad-food-crime against humanity. In an attempt to console the starving stranger, you stress the point that the McDonald hamburgers and Mars bars would do more harm than good. To strengthen your point you suggest him/her to purchase the DVD of the “Super Size Me” documentary (Morgan Spurlock) and you cite a number of key papers, authored by esteemed scientists, in which it was shown that “fast food” causes obesity, cancer and, why not, decreases your self- esteem and that that would be the last thing you want to happen to a starving stranger! Upon arrival in your air-conditioned hotel, you bin the hamburgers and the Mars bars, praise yourself for such consequential behaviour and swear never to buy bad food again (at least not until the next weak moment of self-control).

In face of the 800 million underfed people worldwide, it is simply unethical to qualify essential nutrients as “bad food” (“mal-bouffe” in french) and make it responsible for our overweight, our cancers or our unhappy lives. Food, which we define as plant & animal- or industry-produced substances that can be processed by our digestive tract and our cellular metabolic pathways, and which serve as structural components or as fuel for our body and are devoid of immediate toxic effects, cannot be bad. Instead we may, and perhaps we often do, use food in a bad manner (bad eating habits).
Medicaments

reddot A vast array of physiological processes has been targeted in an attempt to counter obesity. The processes fall into five main groups:

  1. Digestion of food and uptake from the gastrointestinal tract (approved; Orlistat)
  2. Production of post-ingestive hormones by the gastrointestinal tract (team 2)
  3. Fat storage in adipose tissue
  4. Hypothalamic regulation of homeostasis (hormones and neurotransmitters acting in the arcuate nucleus) (team 2)
  5. Dopamine reward circuits (approved until 2010; Sibutramine) (team 3)

reddot Table 1 shows a list of medicaments that have been put on the market in order to “curb appetite and promote weight loss” but were later retrieved because of inacceptable adverse affects.

Year medicament target(s) or therapeutic effect inacceptable adverse effects
1893 thyroid hormones Broad range of cell metabolic processes Palpitations, heat intolerance, nervousness, insomnia, fast heart rate, trembling hands, muscle weakness, staring gaze etc and possible viral infections because these were crude extracts from animals
1934 Dinitrophenol uncoupling agent, reduces ATP production fever, cataract, neuropathie
1937 Amphetamines dopamine reward circuit, locomotor stimulant addiction
1967 Rainbow pills (amphetamine, phenobarbital, thyroid hormone,digitalis) many death
1971 Aminorex locomotor stimulant pulmonary hypertension
1997 Fenfluramine / dexfenfluarmine dopamine reward circuit impairment of cardiac valves, hypertension
2008 Rimonabant inverse agonist of cannabinoid receptor CB1 severe depression, suicidality
2010 Sibutramine dopamine reward circuit cardiovascular accidents

Table 1

Information sources:

Review article

  1. Halford JCG, Boyland EJ, Blundell JE, Kirkham TC, Harrold JA. Pharmacological management of appetite expression in obesity. Nat Rev Endocrinol 2010;6:255-269

Research article

  1. Padwal, R, Li SK, Lau DCW. Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Int J Obesity 2003;27,1437-1446.

Websites

  1. http://www.yourbariatricsurgeryguide.com/
  2. http://nutritiondata.self.com/
  3. http://en.wikipedia.org/wiki/Sibutramine
  4. http://www.abbott.fr/abbott/Accueil/Actualités/Suspension de l’Autorisation d.aspx
  5. http://www.thepainweb.com/doclib/topics/000009.htm

reddot In France, two medicaments have been approved and are widely used for the treatment of obesity, Sibutral (sibutramine, generic name) and Xenical (orlistat, generic name). Sibutral, however, has very recently (21 january 2010) been withdrawn from the European market (see below).

Brand name, generic name, systemic name
Medicaments always come in different names.
  • First of all there is the brand name or trademark®, generally short, catchy, in the hope that people remember. The brand name may differ from country to country, depending who is producing/marketing the drug. For instance Reductil, Meridia or Sibutral are brand names of the same medicament.
  • The generic name sometimes reflects the chemical composition, the origin of the medicament, its function or sometimes nothing. Importantly, generic names are uncoupled from sources or affiliations; they can be considered as genericized trademarks. One of the best examples is aspirin; originally the trademark of Bayer AG*, now a generic name for acetylsalicylic acid, a product that goes under many brand names such as Ascriptin, Bufferin, Cama, Easprin, Ecotrin or Empirin. In the context of this webpage, sibutramine is the generic name of Meridia and Sibutral. Generic names are particularly useful in the world of research and education; one name, one molecule.
  • The systemic name is the name agreed upon by the IUPAC (international union of pure and applied chemistry nomenclature). For sibutramine the systemic name is ((±)-dimethyl-1-[1-(4- chlorophenyl) cyclobutyl]-N,N,3-trimethylbutan-1-amine. These names, except for hardcore chemists, are difficult to decipher, let alone remembe
* Aspirin, acetylsalicylic acid, was first sold as a powder around 1899. The first tablets appeared in 1915. The name was a trademark coined by Bayer: it is composed of the 'A" of acetyl chloride (the acetyl donor), the "spir" of “spirsaure” (acid derived from Spiraea ulmaria, one of the natural sources of salicylic acid) and the 'in' was a then familiar name ending for medicaments. After World War I, as part of the Treaty of Versailles in 1919, Bayer was forced to give up the Aspirin trademark (in France, UK and US), as well as that of Heroin® (another generic name).

Information sources:

  1. http://www.drugs.com/
  2. http://inventors.about.com/library/inventors/blaspirin.htm
  3. http://en.wikipedia.org/wiki/Bayer

1. Sibutral (or sibutramine)

reddot Sibutral was originally developed as an antidepressant but one of the unexpected outcomes of the clinical trials was weight loss of its “subjects”. It has been put on the market as an “appetite suppressant” since 2001. Another trade name is Reductil or Meridia. The active compound, administered orally, is sibutramine, a phenylethylamine derivative (resembling amphetamine) that acts by inhibiting the serotonin-noradrenaline re-uptake transporters (see figure 2). It may affect dopamine re-uptake as well. As a consequence, synaptic levels of serotonin and noradrenaline are elevated (NB serotonin levels may raise more broadly as its release is not exclusively synaptic (giving rise to a diffuse distribution)). The elevated levels of nor-adrenaline will affect the dopamine reward circuits as it has been demonstrated that noradrenaline causes hyperpolarisation of dopamine-containing neurons. Hyperpolarisation of the neuronal membrane leads to a reduced release of the neurotransmitter as it is more difficult to get an action potential that causes neurotransmitter vesicles to fuse with the plasma membrane (and release their content). As discussed by team 3, the subsequent reduction in dopamine levels may have an appetite suppressant effect because it lowers the anticipated reward for food; low dopamine is associated with a lower level of “wanting”. The elevated levels of serotonin may work by causing an advanced onset of satiety and thereby reducing the amount of food intake. Sibutramine also has a thermogenic effect, causing an increased heat production. This means that more fatty acids (and more glucose) are converted into CO2 and H20.

reddot On pooling results from three clinical trials, consisting of a low caloric diet +/- medicament, obese people on sibutramine therapy lost 4,3 kg (4,6% of their weight) more than the placebo (control) group over a period of one year. This therapeutic effect was associated with an increase in blood pressure (both systolic and diastolic), with an increased pulse rate, insomnia, nausea, dry mouths and constipation.

Figure 2 proposed mode of action of Sibutral. Sibutral inhibits re-uptake of a number of neuro-transmitter leading to sustained elevated levels in synaptic clefts. Increased levels of noradrenaline affect the dopamine reward circuits and this may reduce the “wanting” for food. Higher levels of serotonin may advance the onset of satiety.

reddot Until recently, the medicament was produced and distributed by Abbott Laboratories. The adverse affects that have led to the recent retrieval from the market are cardiovascular accidents, such as heart attack and stroke. In some cases it may cause renal (kidney) disfunctioning.

2. Xenical & Alli (or orlistat)

reddot It also comes under different trade names and one generic name, orlistat, and is produced by two companies. Xenical is the name of Roche, a prescription medicament, whereas GlaxoSmithKline has marketed the same product as an over-the-counter medicament known as Alli (see figure 4). It is a lipase inhibitor, preventing triglycerides (fat) in our gut to be converted into fatty acids (see figure 3). The digestive tract is unable to absorb triglycerides (see below) and they therefore remain in the faeces. As a result, about 30% of the fat contained in fat-containing meals is not absorbed. This loss of fat equates to a decrease of ~200 kilocalories per day (remember a reduction of 600 kilocalories is required for meaningful weight loss of obese people).

Figure 3 Pancreatic lipase and lipid uptake in the small intestine

reddot Most lipids are ingested in the form of triglycerides (more precisely, “triacylglycerols” in figure 3) but must be degraded into fatty acids and monoacylglycerol in order to be taken up by the intestinal wall (an epithelium composed of enterocytes). The degradation occurs through enzymes called “lipases”, the majority of which is produced by the pancreas (exocrine function). In order to make the triacylglycerols more accessible to the lipase they are mixed with bile salts that are produced by the liver and released from the gall bladder. An important bile salt is glycocholate. The mixture of bile salts and triacylglycerols leads to the formation of micelles in which the ester bonds of the triacylglycerols orient toward the surface. The lipases digest the triacylglycerols into free fatty acids and mono-acylglycerol (see figure 3). These cross the cell membrane with the help of transporter proteins. Once inside the gut wall, they are converted into triacylglycerol and travel the body, first the lymph then the blood, in the form of chylomicrons, a combination of proteins and lipids (see figure 39 of the French resource on “endocytosis”). These chylomicrons make the plasma (the liquid part of your blood) look opaque, rather than clear and transparent (when little fat is transported). All cells of the body will use the lipids for different purposes. An excess of it will be stored in adipose tissue (for more information about adipose tissue, go to “leptin” in “homeostatic regulation of food intake” of team 2)

Figure 4 Alli and Xenical (both containing 0rlistat)

reddot On pooling results from eleven clinical trials, consisting of a low caloric diet +/- medicament, obese people on Orlistat therapy lost 2.7 kg (2,9% of their weight) more than the placebo (control) group over a period of one year. Secondary outcomes were; a reduction in blood cholesterol levels, a better control of glucose levels and a reduction in blood pressure. These therapeutic effects were associated with gastrointestinal events caused by the fact that the faeces becomes rather fatty/oily (it gets slippery leading to steatorrhea (sort of diarrhoea)). The severity depends of course on the fat content of the foods. Low fat diets will cause less trouble (but the medicament becomes obsolete when you managed to eat less and eat less fat). Furthermore, levels of fat-soluble vitamins (A, D and E) and beta-carotene (pro-vitamin A) decline but not to a level of deficiency (within the duration of the trial).

Bariatric surgery

reddot The above described limited long-term success of behavioural changes (life-style) and of pharmacological intervention in the treatment of severe or morbid obesity has led to a renewed interest in bariatric surgery. Moreover, novel laparoscopic techniques have made this type of surgery less onerous (for the patient, not necessarily for the surgeon). Bariatric surgery remains the most effective treatment for morbid obesity (people with a body mass index higher than 40 kg/m2). In England, weight-loss surgery has increased 10-fold since 2000, with nearly 7000 operations in 2008. Until today, bariatric surgery is considered only for morbid obese patients, who have not succeeded to reduce weight through life-style changes or medication, and for severe obese patients (MBI in between 35-40) with a high risk of morbidity and mortality. Indeed, bariatric surgery can result in substantial weight loss, up to 50% of initial body mass, leading to a resolution of co-morbid conditions and improved quality of life. However, it is not successful for everybody and it is a drastic surgical intervention. The decision process must therefore include a good view of the patient's weight-loss history (his/her personal accountability, responsibility, and comprehension) as wells as a good estimation of the acceptable level of risk. Complications can be numerous and include, amongst many others, technical failure, bleeding, abdominal pain, nausea or vomiting, excess loose skin (occurring in particular with rapid weight loss), bowel obstruction, ulcers, and anastomotic stricture.

reddot To be successful, all surgical procedures described below require strict compliance to diet. For instance, food with high fiber content or dense food may cause discomfort. Furthermore, despite surgery, “rich” food is still to be avoided (reduce fat & sweet food). In short, lifelong monitoring by a multidisciplinary team is deemed essential.

reddot With respect to the surgical procedure, distinction is made between two types:

  1. restrictive procedures (gastric banding)
  2. malabsorptive procedures (gastric bypass)
Some figures for Britain (England, Scotland and Wales)
Britain (or Great Britain) has 62 million inhabitants, of whom 80% is 16 years and older (demographic distribution in 2009), of these 20% is estimated to be obese (body mass index exceeds 30 kg/m2), amounting to 9,92 million persons. Of these, 6953 have sought bariatric surgery in 2007 (only 0,001%) (figure 5).


Figure 5 Bariatric procedures in England (UK) during 2000-2008 (information source BMJ 2010;341:c4296)

Laparoscopic surgery
The term comes from laparo, meaning “abdomen or abdominal wall” and refers to a low invasive surgical procedure in which the handling of the surgical equipment is viewed (scope) inside the body by a small camera (laparoscopic camera). The procedure comprises a small incision (less than 2 cm), near the belly button, the injection of carbon dioxide, to separate the organs of the abdomen, and the insertion of a camera. The camera provides the surgeon with a good anatomical view. It therefore allows the use of long and thin instruments, rather than having to make room for two big hands (as is the case in classic “open” surgery). Advantages are: less post-operational pain, less scarring, minimal risk of incisional hernia, less trauma (faster recovery) and, perhaps, less (nosocomial) infection.

Information sources:

Articles

  1. Karmali S, Stoklossa CJ, Sharma A, Stadnyk J, Christiansen S, Cottreau D, Birch DW. Bariatric surgery ; a primer. Can Fam Physician 2010;56:873-879
  2. Burns EM, Naseem H, Bottle A, Lazzarino AI, Aylin P, Darzi A, Moorthy K, Faiz O. Introduction of laparoscopic bariatric surgery in England: observational population cohort study. BMJ, 2010;341:c4296
  3. C. Roux. De la gastroenterostomie. Revue de chirurgie, 1893, 13: 402-403 (PDF of reprint in Obesity Surgery)

Websites

  1. http://www.obesite-solution-chirurgie.com/
  2. http://en.wikipedia.org/wiki/Adjustable_gastric_band

1) Restrictive procedures

reddot Principle:
Following a meal, the walls of the filled stomach will be distended. Mechano-receptor cells, in particularly in the fundus region, signal the distention to the brain (via the vagal nerve and involving the hormone ghrelin (amongst other mediators)). Because of this, one loses the sense of hunger and instead obtains a sentiment of content because of a full stomach (satiety). Restrictive surgery aims to accelerate the distention of the stomach wall, thus advancing the onset of satiety. As a consequence food intake will be reduced.

reddot Gastric banding:
This procedure exists for over 20 years. It is the least invasive and most reversible procedure which involves the installation of an inflatable silicone band that straps around the fundus region of the stomach (see also figure 2 of team 2). The pouch thus created has a capacity of about 15 ml. The typical empty stomach has a volume of 100 ml, which, in an adult, can be extended to at least to 1000 ml (figures vary from source to source). Food slowly descents from the pouch, through a narrow exit, into the rest of the stomach, like in the hourglass depicted in figure 6a. The tension of the band can be adjusted by letting fluid (saline solution) in or out of the band.

Figure 6 Diagram of (a) adjustable gastric banding and (b) vertical-banded gastroplasty

reddot vertical-banded gastroplasty:
The principle of this procedure is the same as for the gastric band, but this time both a fixed band and staples are used to create the small pouch (figure 6b). This pouch is slightly bigger than the one described above, about 20 ml, and the diameter of the exit hole is fixed (around one-centimeter). This procedure is losing favor because it is not much more effective than the adjustable gastric band and generally regarded more “dangerous”.

2) Malabsorptive procedures

reddot Principle:
Here the reduction of the size of the stomach is accompanied by a bypass of the digestive tract, aiming at a decrease in the absorption of food. Below we briefly describe the digestive process of humans in order to better understand how a bypass affects food absorption (see figure 7).

reddot Digestion starts in the mouth where food is degraded by mechanical mastication (chewing) and by alpha-amylase, an enzyme in the saliva (produced by sublingual, submandibular and parotid glands) that breaks down starch (composed of amylose and amylopectin) and glycogen, yielding maltose and short glucose chains.

reddot In the stomach the masticated food is mixed with: a) high concentrations of hydrochloric acid (HCl), which main role is to disable potential harmful micro-organisms, b) pepsin and gelatinase, enzymes that break down protein, and c) amylase and lipase.

reddot The digestive process gets a real boost in the duodenum, the first 25 cm of the small intestine. Here the pH is restored to approximately 7 (neutral environment), bile salts (produced by the liver and stored in the gallbladder) are added in order to make the lipids more accessible to lipases, and the pancreas releases a whole range of products. Pancreatic products are: trypsin, chymotrypsin, carboxypeptidases and elastase, all of which break down proteins into amino acid fragments, amylase, which breaks down starch and glycogen (and sugar chains that are linked to proteins (glycoproteins)) and nucleases, which break down nucleotides like DNA and RNA. The soupy mixture thus obtained is referred to as chyme.

reddot Further down, in the small intestine, a last series of enzymes is added, predominantly those that break down sugars in their disaccharide form. These are lactase (to split lactose in milk into glucose and galactose), (iso)maltase (to split maltose in two glucoses) and sucrase (to split sucrose in glucose and fructose). The small intestine also releases lipases to further digest lipids. Importantly, the small intestine is the major site for absorption of food, ions and water, a process that requires specific transporter proteins. The small intestine is divided in two sections. The proximal (upstream) part is called the jejunum (~130 cm). Here you find long villi, which together create a large absorptive surface. The epithelial cells of the jejunum harbour high concentration of enzymes and transport proteins (to bring the food inside the body). The distal (downstream) part is called the ileum (~130 cm). It is characterized by shorter villi (less surface), more lymphoid tissue (immune defense) and less absorptive capacity.

reddot The small intestine is followed by the large intestine (~135 cm), comprising appendix, cecum, colon and rectum. It is highly enriched in bacteria (which live in a symbiotic relationship with our body). We (the host) provide the food and they (the bacteria) provide the enzymes (released in the gut) that ferment fibrous carbohydrates (cellulose, amylon, amylopectin) into short-chain fatty acids. These short fatty acid chains are absorbed by the colon epithelium. Bacteria also synthesize type-B vitamins. Apart from its role in digestion, the large intestine also assures water and salt retention (to reduce water loss still further). The waste products, a mixture of undigested food, bacterial flora and shed epithelial cells, pass on to the rectum and are expelled from our body through the anus. To get an idea about volumes; we take in roughly 2 liter of food and drink each day. To this, the digestive system adds: 1.5 liter saliva, 2 liter gastric secretions, 0.5 liter bile salts, 1.5 liter pancreatic secretions and 1.5 liter intestinal secretions. All of this, except for 0.1 liter of faeces, is (re)absorbed in the small (83.4%) and large intestine (15.5%).

reddot The digestive process is greatly hampered when a bypass is created (surgically, see figure 8) that leaves out the duodenum and the larger part of the jejunum. As a consequence, much of the ingested food is wasted.

Information sources:

Book

  1. Silverthorn DU. Human Physiology; an integrated approach. 2009, 5th Edition, Pearson/Benjamin Cummings

Website

  1. To learn about transport proteins, go to our French resource “transport membranaire”

Figure 7 Food passes different organs/anatomical structures, starting from the mouth and ending at the anus (in all, a 450 cm journey). Throughout the passage, different products are added (produced by the body or by bacteria) in order to facilitate the digestive process. See text for a more detailed description. Image adapted from wikibooks.org/wiki/Biologie-humaine/Digestion.

reddot NB the length of the digestive tube is not fixed. It is made up of an inner circular and outer longitudinal layer of smooth muscle cells. These conduct the peristaltic movement that pushes the food to the exit part of the tract. Longitudinal muscle contraction may reduce the length by as much as half.

reddot Gastric bypass type Roux-en-Y Proximal:
A procedure named after the Swiss surgeon César Roux, who first described the surgical procedure in 1893. In this procedure, part of the stomach is closed with staples. The jejunum is cut at approximately 45 cm from the stomach. The proximal part (upstream) is grafted on the pouch created in the stomach. The loose end, containing the duodenum, is grafted back on the jejunum but much more distal, around 70-120 cm (see figure 8a)


Figure 8 (a) The Roux-en-Y bypass. Food does not traverse the duodenum or the upper part of the jejunum and this renders the digestive process much less efficient. Pancreatic enzymes and bile salts only enter the jejunum after roughly 100 cm (near the ileum). Note the Y-shape of the two jejunum sections, hence the name Roux-en-Y bypass.
(b) Biliopancreatic diversion with duodenal switch. The ileum (second part of the small intestine) is directly stitched to the proximal part of the duodenum (before the entry of the ducts of the pancreas and the gallbladder). The duodenum-jejunum is next blocked on one end and connected to the downstream end of the ileum (near the connection with the large intestine). This renders the digestive process very inefficient.

reddot Biliopancreatic diversion with duodenal switch:
Here the stomach volume is only moderately reduced, creating a pouch of ~70 ml. The duodenum is sectioned, just after the stomach. A second cut is made at the border of the jejunum and the ileum (remember, the first and second part of the small intestine respectively). The ileum is stitched to the proximal part of the duodenum (the stomach side). The distal part of the duodenum, containing the ducts of the pancreas and the gallbladder (entry site of the digestive enzymes and the bile salts), is closed. The jejunum is then connected to the ileum (figure 8b). The digestive enzymes and the bile salts only mix with the food at a late stage in the ileum, leaving only a short distance for digestion and absorption.

Information sources:

Books

  1. Walker, Watkins, Duggan; Nutrition in Pediatrics; basic science and clinical applications. 2003, 3rd Edition, BC Decker
  2. Wadden T, Stunkard A. Handbook of obesity traitement. 2004. Eds The Guilford press
  3. Durrer D. Schutz Y. Obésité ; les outils pour le praticien. 2008, Eds Medecine et hygiene
  4. Lecerf J-M Poids et obésité. 2001, Eds John Libbey EUROTEXT
  5. Basdevant A, Guy-Grand B. Traité de medicine de l’obésité. 2004, Eds Flammarion Médecine

Articles

  1. Hyde R. Europe battles with obesity. The Lancet 2008; 371:2160-2161.
  2. Downey D. Obesity and Political Process. Obesity 2008;16:2391-2392.
  3. Bjorn G. As obesity epidemic grows, research shows fitness benefits fetal development’. Nature Medicine, 2008;14:1167.
  4. Korenkov M, Sauerland S, Junginger T. Surgery for obesity. Current Opinion in Gastroenterology 2005; 21:679-683.

Websites

  1. http://www.mangerbouger.fr/
  2. http://www.chirurgie-digestive.com/index.php?fiche=48&sommaire=2
  3. http://fr.wikibooks.org/wiki/Biologie_humaine/Digestion

 

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Last Updated September 1, 2015 9:48 PM | admin news