Temperature & Disease Mechanisms

Energy is required continuously for cell repair and growth and intermittently for work, although intake of food to provide this energy is intermittent. There is loss of nutrient energy when food is converted to mechanical energy; about 65% is dissipated as heat. Twelve people sitting talking in a room produce heat at 60 kJ/min, equivalent to a 1 kW electric fire. Total energy expenditure (TEE) has three components:

• Basal metabolic rate (BMR): at complete rest and without physical work (basal metabolism), energy is required for the activity of the internal organs and to maintain body temperature. This is the single largest contributor to TEE, at 60–70% of TEE. During sleep the overall metabolic rate approximates to the BMR.

• Thermogenic component: the energy expended through the physiological response following the ingestion of food, and exposure to cold or stimulants.

• Physical activity: only 25–35% of nutrient energy is used for mechanical work and less than 10% is for basic physiological activity, e.g. cardiac and respiratory contractions. The energy requirement of an individual is the energy intake that will balance energy expenditure when the individual has a body size, composition and level of physical activity consistent with long term good health, and will allow for the maintenance of economically necessary and socially desirable activity. In children and pregnant and lactating women, the energy level includes the energy need associated with the deposition of tissues and the secretion of milk at rates consistent with good health.

The regulation of body weight is dependent on a balance between nutrient intake and utilization, although there are other important factors.

• The general principle of energy balance and hence body weight is:

Energy consumed = Energy expended + Change in body store

• Amino acid oxidation adjusts to amino acid intake.
• Carbohydrate oxidation adjusts to carbohydrate intake.
• Fat balance is not regulated and nutrient excess goes into stores.
• glycogen reserves are in the order of an average day’s carbohydrate intake. The reserves are maintained at a balanced amount that prevents hypoglycaemia, but excess carbohydrates are channeled into lipid stores
• fat balance does not appear to be regulated in the same manner. Fat oxidation and metabolism are not dependent on the fat content of the meal; fatty meals lead to fat accumulation and obesity. BMR may be determined from the consumption of oxygen and excretion of carbon dioxide and urinary nitrogen, or from the heat production of the animal. Body size is a major factor in TEE and hence BMR. BMR is calculated using the body weight in kilograms/surface area in meters. 

The use of surface area of the body enables comparison of measurements of BMR in individuals of different size. The surface area is calculated from height and weight using nomograms. Body composition is also important, as the fat and lean components of the body have differing resting metabolisms. BMR is more closely related to lean body mass than to surface area. Gender differences are due to the associated, different, gender-related body composition. The energy expenditure varies with age, diet, climate and psychological stress. Metabolic rate calculated from body weight alone can be used as an index of total energy intake for groups of individuals, assuming that the ratio of TEE to BMR is 1.6 on average, although this is not the case in sedentary individuals. Rates of work or energy expenditure are calculated in watts (1 W = 1 kJ/s). Changes in energy metabolism are due to the effect of and interactions between the environmental and biological factors that influence metabolism. 

The Brody–Kleiber metabolic equation attempts to predict the basal metabolism of all. Inappropriately high intakes or low expenditure produce energy excesses, increase fat storage and result in a gain in body weight. Ein is the energy available for metabolism of the foods and Eout is formed from two components: 

Eout = Eexer + Ether, where Eexer is the energy available for metabolism of the foods lost from the body in urine and faeces, and Ether is heat production (thermogenesis). The thermic effect of physical exercise will vary according to the intensity of work performed and the duration of activity. A 70 kg man requiring a maintenance energy intake of 10.5 MJ (2500 kcal)/day will require 3.2 MJ (750 kcal)/day or 30% of these energy requirements for muscular activity. Clearly, the thermic effect of physical energy will be the most variable of all the components of

Ether. 

The metabolic efficiency of physical work is approximately 30%. Adaptive thermogenesis is believed to account for no more than 10–15% of total energy expenditure, but may be important in the long term. This may be due to a change in RMR due to adaptation to environmental stress, e.g. temperature, food intake, emotional stress, and other factors. During undernutrition there is a progressive decline in the RMR. During over-nutrition there is an increase in RMR in the order of 10–15%. These changes are in part due to sympathetic nervous system activity, adrenaline, thyroid hormones and insulin. Thermogenesis is the increase above BMR caused by the thermic effect of food intake. It is a by-product of cellular and body maintenance, the thermic effect of food, the thermic effect of physical exercise, exercise heat production and the phenomenon of adaptive thermogenesis. The thermic effect of food is an increase in energy expenditure over the RMR following a meal. Heat is produced in response to an alteration in metabolic efficiency associated with changes in environmental conditions. The relative contribution of each to the TEE can be calculated. The effect of diet is complex and not well understood. All elements of diet are thermogenic. This is in part due to the energy required for digestion, absorption, transport, metabolism and storage of the ingested food. There may be other influences on the sympathetic nervous system by dietary carbohydrates. The thermic effect of food is said to be approximately 10% of calorie intake, although the effects of specific nutrients may vary. A complex network of dietary and hormonal factors acts to regulate diet-induced thermogenesis in humans. In determining the response to food, the thermic effect of food is complex and not consistent, e.g. between obese and lean subjects. Part of the difference may be due to insulin resistance associated with obesity. It has been suggested that exercise plays a role in energy balance, both by expending energy and by regulating food intake. Aerobic fitness and the timing and size of a meal are determinants of the metabolic response to exercise, and account for some of the differences between lean and obese subjects. The sympathetic nervous system and the indirect effects of adrenaline and noradrenaline may be involved in some of the changes. Thus, the type of nutrients in food, the substrates that result from the ingestion of that food, and the signal triggered by that food, all play a part in thermogenesis. Undoubtedly, fasting suppresses and sucrose stimulates sympathetic activity. In addition to insulin mediating glucose metabolism, thyroid hormones are important. The effect on energy metabolism following carbohydrate overfeeding may result from energy requiring processes that are quite different from those induced by a mixed meal. This may result from differences in the metabolic fate of the carbohydrate. A proportion of ingested glucose, if in excess, is converted into lipid rather than oxidized or converted into glycogen. Lipogenesis from glucose is relatively inefficient. It is possible that the thermogenic effect of fat is mediated by free fatty acids or the hormones that are stimulated by such fatty acids. It is probable that proteins produce a larger and more sustained thermic response than carbohydrate or fat. This may well reflect the energy cost of the synthesis of tissue proteins. Skeletal muscle is involved in more than half the total protein turnover, and the fasting-state fall in muscle synthesis can account for most of the change in whole body turnover. This has implications for energy expenditure and metabolic rate, which may reflect changes in protein synthesis.

The term “energy balance” refers to the integrated effects of diet, physical activity, and genetics on growth and body weight over an individual’s lifetime, including the mechanistic pathways through which physical activity and diet exert their effects. Scientists are increasingly aware of the importance of understanding the effects of energy balance on the development and progression of cancer and in cancer patients’ quality of life during and after treatment (U.S. Department of Health and Human Services [U.S. DHHS], 2004). Indeed, a 2003 Institute of Medicine (IOM) report on cancer prevention and control assigns top priority to the development of a national strategy to prevent obesity and sedentary behavior (Curry et al., 2003). The prevalence of overweight and obesity has increased dramatically in the past 2 decades in the United States (Hedley et al., 2004). Among adults 20 years or older in 1999–2002, 65.7% were overweight (body mass index [BMI]  25.0– 29.9), 30.6% were obese (BMI ≥ 30.0), and 5.1% were extremely obese (BMI  40). On average, this translates to an average gain of  20 pounds in both men and women between the early 1960s and 2002, while during the same time period mean height increased by ~1 in. (Ogden et al., 2004). Over the same years, mean BMI increased ~3 BMI units in both men and women as well (Ogden et al., 2004). Although this trend has appeared across all ethnic groups and genders, it has occurred disproportionately in members of specific ethnic groups, particularly African Americans, Hispanic whites, and American Indians. Of particular concern is that these same trends have also appeared in children, with ethnic group disparities similar to those in adults (Hedley et al., 2004). The level of physical activity of U.S. citizens at work and during daily living has been decreasing for decades. Less than 40% of American adults get regular exercise, and some 25% get no activity at all.

Similar, maybe even more severe, problems exist for our children, where half of American youths do not engage in vigorous physical activity on a regular basis (U.S. DHHS, 1996). Studies have found that physical activity declines steadily and steeply after childhood. In addition to these ominous trends, daily enrollment in physical activity classes in high school has also steadily declined over the past 2 decades (U.S. DHHS, 1996). Reversing these trends is essential, because physical activity plays a direct role in health and well-being, and inactivity is a major factor in the obesity epidemic that is affecting our population. Obesity in adults is associated with increased mortality from cancers of the colon, breast (in postmenopausal women), endometrium, kidney (renal cell), esophagus (adenocarcinoma), gastric cardia, pancreas, prostate, gallbladder, and liver in a cohort of men and women aged 57 years in 1982, known as the American Cancer Society (ACS) study (Calle et al., 2003). Estimates from the ACS study, the largest prospective analysis of the weight–cancer relationship, suggest 14% of all cancer deaths in men to 20% of all cancer deaths in women from a range of cancer types are attributed to overweight and obesity (Calle et al., 2003). In addition, a study based on the National Health and Nutrition Surveys (NHANES) I, II, and III, as well as the NHANES 1999–2002, identified those in both the leanest and the highest level of BMI at increased risk of all cause mortality (Flegal et al., 2005). If one examines the NHANES data and the ACS data by birth cohort, the findings are quite similar, indicating the importance of events across the life course and their influence on energy balance and mortality.

An International Agency for Research on Cancer (IARC) Working Group on the Evaluation of Weight Control and Physical Activity (2003) concluded that the avoidance of weight gain reduces the risk of developing cancers of the colon, breast (in postmenopausal women), endometrium, kidney, and esophagus based on epidemiological studies of overweight and/or obese compared with leaner individuals. The IARC Working Group Report also concluded that there is consistent epidemiological evidence for a protective effect of physical activity for some cancers. However, the report stated that the relationship between energy balance and cancer is poorly understood. Furthermore, obesity prevention and treatment regimens are difficult, and research on cancer risk in people who have lost weight is extremely limited (Ogden et al., 2003; Calle et al., 2004). In addition, surprisingly little is known about the mechanisms through which caloric restriction or physical activity (the major lifestyle-based strategies for reducing/maintaining weight) exert their anticancer effects (Rundle et al., 2005).