To date, there have only been a modest number of structured and evaluated interventions, which have had a primary objective of preventing or limiting weight gain. However, a broader range of projects have examined the most effective strategies for improving physical activity or encouraging specific dietary change or for combating allied chronic noncommunicable diseases such as CHD, hypertension, and diabetes. Examining the lessons learned from these programs allows a preliminary perspective on the potentially most suitable approaches to supporting and encouraging the prevention of weight gain in the community.
Once the mutagenesis is achieved, dietary resistant mutants and oxidative stress resistant mutants could be selected which might suggest genes involved in such a mechanism. For example a paraquat resistance mutant could be selected and then tested for lifespan extension. Similarly, mutants could be fed with a high fat and high nutrient diet which, in contrast to dietary restriction, should shorten the lifespan and the mutants that live under these conditions could be selected. However, these require careful feeding experiments. Likewise, by feeding -3 fatty acids, the mutants that do not prolong the lifespan in the presence of -3 fatty acids could be selected. All these imaginative screens will be feasible once the Nothobranchius model is available as a genetic model.
The energy balance equation is a logical place to start trying to understand obesity at the individual and population level. The most accurate version of the energy balance equation is the ''dynamic, physiological'' version (15) which incorporates rates of change (16) and an interconversion between energy balance and fat balance (17,18). While this equation has served reasonably well as a model for understanding weight gain and obesity at an Figure 1 An ecological model of obesity. Figure 1 An ecological model of obesity.
Rats fed a purified nonlipid diet containing vitamins A and D exhibit a reduced growth rate and reproductive deficiency which may be cured by the addition of linoleic, a-linolenic, and arachidonic acids to the diet. These fatty acids are found in high concentrations in vegetable oils (Table 14-2) and in small amounts in animal carcasses. These essential fatty acids are required for prostaglandin, thromboxane, leukotriene, and lipoxin formation (see below), and they also have various other functions which are less well defined. Essential fatty acids are found in the structural lipids of the cell, often in the 2 position of phospholipids, and are concerned with the structural integrity of the mitochondrial membrane.
Many medications used to treat mental disorders promote weight gain, including Dietary treatments for individuals taking these medications should focus on a balanced, low-fat diet coupled with an increase in physical activity to counter the side effects of these medications. Nutrient-rich foods such as fruits, vegetables, and whole grain products should be emphasized in the diet, whereas sweets, fats, and other foods high in energy but low in nutrients should be limited. Regular physical activity can help limit weight gain caused by these medications. Lithium is often used to treat individuals with mania. Lithium can cause nausea, vomiting, anorexia, diarrhea, and weight gain. Almost one-half of individuals taking lithium gain weight.
These risk factors will be considered together because they are closely intertwined. In particular, management of physical inactivity is one therapy for obesity. Approaches to management of overweight obesity including the following The first three are standard therapies. Pharmaco-therapy and surgical therapy are reserved for special cases. They are used mainly for more severe forms of obesity, particularly to control comorbidities. Theoretically, they could be considered for patients with type 2 diabetes, although they have not been thoroughly evaluated in such patients. The following approach to weight loss in overweight obese persons at risk for cardiovascular disease or type 2 diabetes is taken in large part from recommendations of the OEI report (1,2).
The purpose of weight loss and weight maintenance is to reduce health risks. If weight is regained, health risks increase once more. The majority of persons who lose weight regain it, so the challenge to the patient and the practitioner is to maintain the weight loss. Because of the tendency to regain weight after weight loss, the use of long-term medication to aid in the treatment of obesity may be indicated in some carefully selected patients.
The recent and relatively rapid rise in the prevalence of obesity occurring over a timescale which would make conventional evolutionary explanations implausible has, understandably, led some to question the importance of genetics in the etiology of obesity. There are some obvious candidates for the causation of secular changes in obesity prevalence including the increased availability of palatable energy dense foods and the reduced requirement for physical exertion during working and domestic life. It is therefore timely to review the evidence for inherited determinants of obesity and related intermediate traits. We will focus on data from twin and adoption studies as these are the most powerful tools to address this question.
It is well established that obesity runs in families, although the vast majority of cases do not segregate with a clear Mendelian pattern of inheritance. There are about 30 Mendelian disorders with obesity as a clinical feature but often associated with mental retardation, dysmorphic features and organ-specific developmental abnormalities (i.e. pleiotropic syndromes). A number of families with these rare pleiotropic obesity syndromes have been studied by linkage analysis and the chromosomal loci for obesity syndromes are known. For a comprehensive list of syndromes in which obesity is a recognized part of the phenotype, see Online Mendelian Inheritance in Man (OMIM), www.ncbi.nlm.nih.gov omim .
In the past eight years several human disorders of energy balance that arise from genetic defects have been described. All of these are in molecules identical or similar to those known to cause obesity in genetic and experimental syndromes of obesity in rodents (Leibel et al., 1997) and all have been identified using a candidate gene approach (Figure 22.2). These mutations all result in morbid obesity in childhood without the developmental pleiotropic features characteristic of the recognized syndromes of childhood obesity.
In experimental animals, vitamin E deficiency results in resorption of fetuses and testicular atrophy. Dietary deficiency of vitamin E in humans is unknown, though patients with severe fat malabsorption, cystic fibrosis, and some forms of chronic liver disease suffer deficiency because they are unable to absorb the vitamin or transport it, exhibiting nerve and muscle membrane damage. Premature infants are born with inadequate reserves of the vitamin. Their erythrocyte membranes are abnormally fragile as a result of peroxidation, which leads to hemolytic anemia.
As chromium has a role in maintaining carbohydrate and lipid metabolism, and potentiating insulin action, it has been suggested that chromium supplementation may have effects on body composition, including reducing fat mass and increasing lean body mass (Vincent 2003). A meta-analysis of RCT concluded that chromium picolinate elicited a relatively small effect compared with placebo for reducing body weight (Pittler et al 2003). One study, however, did show promising results using 200 g chromium bound to niacin three times daily (total 600 g day) with moderate exercise. At these high doses, while overall reduction in body weight was similar for both the chromium and placebo groups, total fat loss was more significant in the chromium group, suggesting a muscle sparing effect (Crawford et al 1999).
Dietary restriction is the only environmental manipulation that can bring robust extension of lifespan in a variety of model organisms, and is one of the most important themes in aging studies. Despite a great deal of effort, the precise mechanisms by which it works are not clear. Exploration of its mechanism has also been Using demographic analyses, it has been shown that dietary restriction extends lifespan in flies by altering baseline mortality rate without altering the rate of aging (Mair et al., 2003). (Figure 22.1).
Synephrine produces effects on human metabolism, which could be useful for reducing fat mass in obese humans because it stimulates lipolysis, raises metabolic rate and fat oxidation through increased thermogenesis (Pellati et al 2002). A controlled in vivo study of C. aurantium fruit hydro-alcoholic extracts standardised to synephrine 4 (Ci.au. 4 ) and 6 (Ci.au. 6 ) found repeated administration of the extract significantly and dose-dependently reduced food intake and body weight gain (Calapai et al 1999).
It has been shown that dietary melatonin directly contributes to the circulating level of the hormone. The clinical effects of plant-derived melatonin remains to be investigated (Hardeland & Poeggeler 2003). Baicalin itself is poorly absorbed from the gut, but is hydrolysed to its aglycone, baicalein, by intestinal bacteria and then restored to its original form from the absorbed baicalein in the body (Akao et al 2000).
Where and denote the mean weight loss of the respective populations. Assume that 30 girls who want to lose weight are available to participate in the experiment. The researcher assigns n 15 girls to each of the p 2 diets so that each of the (np) (n )p 155,117,520 possible assignments has the same probability. This is accomplished by numbering the girls from 1 to 30 and drawing numbers from a random numbers table. The first 15 numbers drawn between 1 and 30 are assigned to treatment level a1 the remaining 15 numbers are assigned to a2. The layout for this experiment is shown in Figure 1.1. The girls who were assigned to treatment level a1 are called Group1 those assigned to treatment level a2 are called Group2. The mean weight losses of the two groups of girls are denoted by Y 4 and Y 2.
A neoadjuvant or adjuvant treatment should be offered only to fit patients without important comorbidities. Crucial in good tolerance, especially for the postoperative chemo-radiotherapy, is the ability of the patient to have an adequate calorie intake during the treatment. Adequate measures are therefore necessary, including the administration of enteral nutrition where required.