Which of the following hormones has the greatest effect on the overall metabolic rate?

Basal Metabolic Rate

The basal metabolic rate (BMR) is the energy expenditure of lying still at rest, awake, in the overnight postabsorptive state. The resting metabolic rate (RMR) is similarly defined but is not necessarily measured before arising from bed. For most sedentary adult Americans, the RMR represents the major portion of energy expended during the day and may range from less than 1200 to more than 3000 kcal/day. Most (~80%) of the variability in BMR can be explained by how much lean and fat tissue an individual has. In addition, BMR is slightly lower in women than men and older than younger adults even after accounting for the amount of lean and fat tissue. There is evidence for heritable or family factors that influence BMR, accounting for as much as 10% of the interindividual differences. There are both obligatory and facultative components to RMR. With an energy-restricted diet, significant reductions in BMR relative to the amount of fat-free mass occur. Reductions in the production of triiodothyronine from thyroxine and the sympathetic nervous system drive are thought to contribute to this phenomenon. Likewise, during brief periods of overfeeding, RMR increases slightly above that which would be expected for the amount of lean tissue present. There are a number of formulas that can be used to estimate BMR. The Harris-Benedict formula (available through numerous online calculators) predicts BMR on the basis of height, weight, age, and sex and is accurate to within 10% in approximately 90% of adults with BMIs of 18.5 to 45 kg/m2.

In contrast to what is typically thought, muscle accounts for only 25% of RMR, but during exercise muscle can account for 80 to 90% of energy expenditure. Adipose tissue is a minor contributor to daily energy expenditure, consuming only approximately 3 kcal/kg of body fat per day.

Brown fat is adipose tissue that expresses large amounts of uncoupling protein-1, a protein that allows a mitochondrial membrane proton leak,resulting in heat release as opposed to chemical work from adenosine triphosphate—“uncoupling” of substrate oxidation from chemical or mechanical work. This thermogenic tissue was thought to be present only in human infants but does exist in small amounts in adults. Because of the high metabolic activity of brown adipose tissue and its potential role in stimulating energy expenditure (i.e., resting energy expenditure and possibly thermogenesis) it is an attractive target for interventions to reduce adiposity. Methods used to detect brown fat largely rely on18F-fluorodeoxyglucose positron emission tomography scanning of humans exposed to cold.

Measurement of BMR is sometimes helpful in the evaluation of patients who insist that they are unable to lose weight while following diets containing less than 1000 kcal/day. Almost without fail, if BMR is measured with a reliable instrument, it is substantially greater than the reported food intake. This underscores the fact that most adults are unreliable in assessing their own food intake.

Glossary

BMR

Basal metabolic rate: The rate of oxygen uptake at rest in the fasting and thermo-neutral state.

Metabolic equivalent is a unit of energy expenditure typically used by those concerned with sports where 1 MET is approximately 1 kcal min−1.

Non-exercise activity thermogenesis. This refers to the cost of energy involved in spontaneous activity rather than deliberate exercise.

Physical activity level: The ratio of the total energy expenditure on a 24 h basis divided by the BMR expressed over the same time period.

Physical activity ratio: This is the total energy cost when active divided by the measured or predicted BMR.

Basal Metabolic Rate

Thyroid hormones increase energy expenditure and heat production, as manifested by weight loss, increased caloric requirement, and heat intolerance. Because it is impractical to measure heat production directly, the basal metabolic rate (BMR) measures oxygen consumption under specified conditions of fasting, rest, and tranquil surroundings. Under these conditions, the energy equivalent of 1 L of oxygen is 4.83 kcal.

Under basal conditions, approximately 25% of oxygen consumption is due to energy expenditure in visceral organs, including the liver, kidneys, and heart; 10% occurs in the brain, 10% in respiratory activity, and the remainder in skeletal muscle. Because energy expenditure is related to functioning tissue mass, oxygen consumption is related to some index thereof, most often body surface area. Calculated in this way, basal oxygen consumption (resting energy expenditure) is higher in men than in women and declines rapidly from infancy to the third decade and more slowly thereafter. Values in patients, calculated as a percentage of established normal means for sex and age, normally range from −15% to +5%. In severely hypothyroid patients, values may be as low as −40%, and in thyrotoxic patients, these values may reach +25% to +50%. Abnormal, usually elevated, values are seen during recovery in burn patients and in those with systemic disorders, such as febrile illnesses, pheochromocytoma, myeloproliferative disorders, anxiety, and disorders associated with involuntary muscular activity. Resting energy expenditure correlates very well with the free T4 and TSH in hypothyroid patients given varying doses of exogenous levothyroxine.218

Basal Metabolic Rate

The basal metabolic rate (BMR) has a long history in the evaluation of thyroid function. It measures oxygen consumption under basal conditions of overnight fast and rest from mental and physical exertion. Because standard equipment for the measurement of BMR might not be readily available, the BMR can be estimated from the oxygen consumed over a timed interval by analysis of samples of expired air. The test indirectly measures metabolic energy expenditure or heat production.

Results are expressed as the percentage of deviation from normal after appropriate corrections have been made for age, gender, and body surface area. Low values are suggestive of hypothyroidism, and high values reflect thyrotoxicosis. Normal BMR ranges from negative 15% to positive 5%, most hyperthyroid patients having a BMR of positive 20% or better and hypothyroid patients commonly having a BMR of negative 20% or lower. Different clinical states are known to alter BMR. Fever, pregnancy, pheochromocytoma, adrenergic agonist drugs, cancer, congestive heart failure, acromegaly, polycythemia, and Paget’s disease of the bone are known to increase BMR. Obesity, starvation or anorexia, hypogonadism, adrenal insufficiency, Cushing’s syndrome, immobilization, and sedative drugs are known to decrease BMR.

Basal Metabolic Rate

Thyroid hormone stimulates basal metabolic rate primarily by increasing ATP production for metabolic processes and by maintaining ion gradients (Na/K+ and Ca2+), which consume ATP. Thyroid hormone is a key driver of thermogenesis. It uncouples oxidative phosphorylation in mitochondria and reduces activity of shuttle molecules that transfer reducing equivalents into the mitochondria. Thyroid hormone also increases sensitivity to catecholamine effect, which is required for maintenance of core body temperature.36

Clinically, the calorigenic action of thyroid hormone affects circulation by increasing heart rate, stroke volume, and cardiac output. The pulse pressure is widened mainly by a decrease in the diastolic pressure and by some elevation in the systolic pressure. Circulation time is also shortened.

Basal Metabolism Rate and Weight

The basal metabolic rate (BMR) is the amount of energy that is expended at rest in a neutral environment after the digestive system has been inactive for about 12 hours. It is the rate of one’s metabolism when waking in the morning after “fasting” during sleep.

The BMR is enough energy for the brain and central nervous system, heart, kidneys, liver, lungs, muscles, sex organs, and skin to function properly. People who are overweight or obese do not necessarily have a slow BMR. In fact, their BMR is usually faster to accommodate for extra fat and for their body to work harder to perform normal body functions. Building lean muscle mass can increase BMR, but there is a limit for both men and women as to how much lean muscle mass can be built. Some supplements may increase BMR, but also only to a limit, and they may have serious side effects (see “Diet aids”).

Expending extra calories through increased physical activity is the most sensible way to increase metabolism. When a person diets, BMR slows down to conserve energy and protect vital organs. A regimen of reasonable dieting with increased exercise maintains or increases BMR and promotes weight loss and weight maintenance. It all depends on calories and caloric balance.

Basal Metabolic Rate

The basal metabolic rate (BMR) is the rate of energy expenditure of a person at rest; it eliminates the variable effect of physical activity. The BMR accounts for approximately 60% of the daily energy expenditure. Thus it includes energy used for normal body cellular homeostasis, cardiac function, brain and other nerve function, and so on. It is related to body weight by the calculation:

BMR(Cal/d)=24×Body weight(kg)

A passive increase in energy expenditure occurs during digestion of food. This is referred to as the thermic effect or, in the older literature, specific dynamic action of food; it accounts for about 10% of the daily energy expenditure.

The total daily energy expenditure is calculated from knowledge of the BMR and a physical activity factor. The physical activity factor is a function of the type of activity for an individual (e.g., 1.3 for sedentary, 1.5 for moderately active, and 1.7 for extremely active). When multiplied by the BMR, an estimate of the daily energy expenditure is obtained.

Example: A 220 lb (220/2.2 = 100 kg) person with moderate energy expenditure (e.g., a cabinet maker):

BMR=24×100 =2400kcal/dayEnergy expenditure=2400×1.5=3600 kcal/day

Energy Expenditure Consists of Basal Metabolism Plus Activity Increment

The basal metabolic rate, BMR, is defined as the metabolic rate during rest but while the person is awake. The person should be in a postabsorptive state, not having eaten within the last 12 hours. The person should also not have strenuously exercised within the previous 12 hours. The air in the room should be comfortable with all sources of excitement removed. The BMR is usually determined by indirect calorimetry by measuring Q O2, the rate of oxygen consumption. The resting energy expenditure (REE) differs from the BMR in that the determination of the REE does not require fasting for 12 hours.

Body size, composition, age, and gender have marked effects on the BMR. The overall volume of the body increases approximately according to the cube of the linear dimensions, whereas the surface area increases according to the square. Thus larger people have a smaller surface area to volume ratio. Since body heat must be shed on the surface, this means that larger people must produce less heat per unit body dimension, or they will get too hot too easily. Max Rubner (1854–1932) showed in 1883 that mouse, dog, man, and horse had greatly different BMR when expressed per unit body weight, but they were all very similar when compared per unit surface area. Based on the geometric argument above, Rubner proposed that BMR=KM2/3, where M is the mass and K is a constant. The exponent of 0.67 in Rubner’s equation is the subject of some debate. Max Kleiber reevaluated the effect of body size on metabolism and found an exponent of 3/4 (actually 0.754). Although the absolute differences in these exponents (0.67 vs 0.75) does not seem large, much has been made of a 2/3 or 3/4 power law because it was thought to be one of the few unifying principles of biology that applied equally well to microorganisms as to elephants. It is likely that no single process determines either the preexponential or exponential factor in the allometric formula:

[8.6.8]BMR=aMb

It is likely that herbivores have a different relationship between BMR and M because of their extensive microbial activity and their nearly continuous state of feeding. Inclusion of herbivores in regressions of BMR against M skews the curve.

Basal Metabolic Rate and Resting Fed Metabolic Rate

Basal metabolic rate (BMR) contributes the greatest portion of an animal’s total energy expenditure. It is defined as the amount of energy expended while an animal is resting in a thermoneutral environment and in a postabsorptive state (i.e., after an overnight fast). BMR represents the energy cost of maintaining homeostasis in all of the integrated systems of the body during periods of rest, when the body is not digesting food. Homeostasis refers to a state of internal stability within the body. A related value is the resting fed metabolic rate (RFMR), which is measured when the animal is not in a postabsorptive state and so includes the heat produced when food is consumed (dietary thermogenesis). The RFMR accounts for approximately 60% to 75% of an animal’s total daily energy expenditure. Factors influencing RFMR include sex and reproductive status, thyroid gland and autonomic nervous system function, body composition, body surface area, and nutritional state.1

Research has shown that BMR and RFMR are positively correlated with the total amount of respiring cell mass present in the body. Fat-free mass or lean body mass is the closest approximation available of the total respiring cell mass. The amount of fat-free mass or lean body tissue is the strongest predictor of an animal’s metabolic rate, followed by body surface area and body weight (BW).4,5 As a pet’s lean body mass and body surface area increase, BMR and RFMR increase proportionately. Similarly, when an animal becomes overweight and experiences an increase in body fat and a decrease in the proportion of lean tissue to total BW, energy expenditure per unit BW decreases.6

Reference values

The BMR reference values include the following:

The Harris–Benedict equation, (Harris–Benedict 1919) one of the most widely used to estimate BMR. This equation is widely used in adults and has never been validated for children.

The Food and Agriculture Organization, the World Health Organization, and the United Nations University (FAO/WHO/UNU). These equations were based on data derived from 6100 individuals under a variety of conditions and represent BMR.

Talbot published guidelines in 1938 for the estimation of BMR based on measurements made in children. These values were based on studies performed by the author.

Schofield equations. These equations were based on data from the FAO/WHO/UNU report with some additional data (Table 1). It is important to mention that the use of these reference values in critically ill patients could lead to underfeeding or overfeeding because of the variability of the metabolic state of patients during their stay in the ICU.

Table 1. Prediction equations

FAO, Food and Agriculture Organization; WHO, World Health Organization; UNU, United Nations University. Basal metabolic rate estimate in kcal per day; weight (Wt) in kg; height (Ht) in cm; physical activity (PA).