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Factors Affecting Energy Metabolism: Sarcopenia

Continuing with citations from my article in Obesity Reviews on an aeteological framework for assessing obesity, we continue discussing factors that can affect metabolic rate:

Sarcopenia

The importance of fat-free mass as the key determinant of resting metabolic rate, even in a very obese individual [sic], cannot be over emphasized. Obese individuals [sic] can present with wide variations in lean body mass, almost entirely accounted for by differences in skeletal muscle mass. Thus, any change in muscle mass can markedly affect basal energy requirements. In this context it is important to remember that in ambulatory individuals, the mass of weight‐bearing muscles is directly proportional to BMI, as heavier individuals require a greater skeletal muscle mass to support and move their excess weight. This alone accounts for much of the higher basal and activity‐related energy requirements of larger individuals.

Although inactivity may be the most common cause of decreased skeletal muscle mass and reduced basal metabolic needs in obese individuals [sic], it is important to consider other causes of muscular atrophy that can likewise markedly reduce energy demands. A wide range of nutritional, neuromuscular, endocrine, renal, cardiac, pulmonary, inflammatory, infectious or neoplastic conditions can result in muscular wasting and sarcopenia. Reduced skeletal muscle mass and weight gain is also noted after many cancer treatments, although the mechanisms remain unclear. Any reduction in skeletal muscle mass not accounted for by a decrease in physical activity and ambulation should prompt investigations for other causes of muscular wasting.

Commentary: Sarcopenic obesity is perhaps even more prevalent than most people may think – especially in people who have slight overweight or even moderate obesity. It is particularly common in certain ethnic groups such as South Asians, even at “normal” BMIs. Clinically, this is where body composition studies can be helpful. Although a reduction in muscle mass does reduce resting metabolic rate (RMR), it is important to remember that overall skeletal muscle only accounts for about 15% of RMR. This is why, the notion that building up muscle mass will help with weight loss by burning more calories is not really an effective weight loss strategy.

@DrSharma
Edmonton, AB
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Factors Affecting Energy Metabolism: Neuroendocrine Factors

Continuing with citations from my article in Obesity Reviews on an aeteological framework for assessing obesity, we continue discussing factors that can affect metabolic rate:

Neuroendocrine Factors

Across the entire age continuum, a wide range of neuroendocrine factors can not only affect metabolic rate, but also substrate partitioning and utilization, which may directly or indirectly contribute to weight gain. The latter point is of particular significance as low rates of fat oxidation are associated with an increased risk of weight gain.

A wide range of neuroendocrine hormones and biomarkers can affect energy metabolism; sympathetic nervous system activity and thyroid function are two major factors directly influencing resting energy expenditure.

Sympathetic nervous activity is also a major determinant of post‐prandial thermogenesis and the thermogenic response to a glucose load has been shown to be significantly lower in obese [sic] individuals, a finding that persists even with substantial weight loss.

Specific examples of endocrine hormones that affect energy metabolism and substrate partitioning include cortisol, growth hormone (GH) and testosterone.

Catabolism associated with hypercortisolism or Cushing’s syndrome can reduce energy requirements and increase the deposition of truncal fat.

Discontinuation of GH treatment at the end of childhood growth in individuals with GH deficiency markedly increases fat mass and decreases metabolic rate, whereas GH treatment in GH‐deficient adults has beneficial effects on protein metabolism, energy expenditure and thyroid metabolism.

Testosterone deficiency can also result in abnormal energy partitioning, which adversely alters anabolism and reduces metabolic rate.

It is important to note that a careful history and physical examination should precede any endocrine testing for these disorders, as testing should be reserved for patients with an above‐normal pretest probability for one of these conditions.

Commentary: as pointed out in the last paragraph, while all of the above are important considerations, each one is quite rare, which is why it is important to use clinical judgement in recognising  these factors, rather than simply ordering a battery of endocrine tests on every patient.

@DrSharma
London, ON

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Factors Affecting Energy Metabolism: Genetics, Sex, and Aging

Continuing with citations from my article in Obesity Reviews on an aeteological framework for assessing obesity, we now turn to the some of the factors that can affect metabolic rate:

Genetics
Because heritable factors appear to be responsible for 45–75% of the inter‐individual variation in body mass index (BMI), the potential impact of genetic determinants of metabolic rate upon the predisposition to obesity must be considered. While numerous somatic and mitochondrial genes with potential effects on metabolic rate have been identified, their contribution to human obesity has yet to be defined Likewise, although there is preliminary evidence for intrauterine and perinatal programming of genes involved in energy metabolism, their role in human obesity remain unclear. What is apparent is that the genetic predisposition to obesity (including both energy intake and metabolism) is not explainable on the basis of a small number of common mutations exerting substantial effects on the individual tendency to weight gain. Thus, a great deal of work is still required before investigation into the multitude of genetic determinants of body weight can potentially impact clinical management. Currently, a careful clinical assessment of family history of obesity and related risk factors remains the best measure of genetic risk for obesity.

Sex
There is a clear effect of gender [sic] on metabolic requirements, whereby, for the same BMI, women consistently display lower metabolic rates (approximately 20% less) than men, largely accounted for by differences in fat‐free mass (FFM).

Aging
Aging is an important determinant of a decline in metabolic rate, with an estimated reduction of around 150 kcal per decade of adult life. Factors that result in the age‐related decline in energy requirements include changes in neuroendocrine factors (e.g. sympathetic activity, thyroid function, etc.) as well as a reduction in skeletal muscle quantity and quality (resulting from reduced physical activity, reduced protein intake and other less‐well‐understood factors).

Additional factors that can affect metabolic rate will be discussed in subsequent posts.

@DrSharma
Edmonton, AB

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A Low Metabolic Rate Will Predispose You To Obesity

Continuing with citations from my article in Obesity Reviews on an aeteological framework for assessing obesity, we now turn to the importance of metabolic rate:

Any assessment of obesity should begin with an estimate of energy requirement – specifically recognizing that any decrease in metabolic rate, without a corresponding decrease in energy intake and/or increase in activity will result in weight gain. Thus, in anyone presenting with weight gain, without any notable change in energy intake or activity levels, it is safe to assume that the only explanation can be a reduction in energy metabolism.

As a rule of thumb: the lower the total energy requirements, the greater the risk of obesity (simply stated: over‐eating is less likely for someone who needs 4000 kcal d−1 than for someone who needs 1500 kcal d−1). In sedentary individuals, resting metabolic rate is responsible for dissipating the vast majority of daily ingested calories (60–75%) and is therefore a key determinant of energy expenditure. Thus, even a small, sustained percentage reduction in resting metabolic rate, without a compensatory adjustment of energy intake or activity, can account for a large cumulative caloric excess over time (e.g. an unbalanced 3% reduction in resting metabolic rate in an individual with a total energy expenditure of 1800 calories can lead to a caloric excess of 32.4 kcal d−1, which can translate into 972 kcal excess per month).

Numerous factors can determine and/or affect metabolic rate. These include genetic and epigenetic factors, gender, aging, neuroendocrine function, sarcopenia, metabolically active fat, certain medications and prior weight loss.

Commentary: of course the numeric relationship between caloric intake and weight gain is not as straightforward as many people may think. This is because changes in caloric balance will in turn change caloric expenditure – remember, we are dealing here with physiology, not physics! Thus, a 20 kcal daily excess will only lead to weight gain until the higher body weight uses up the extra 20 kcal to maintain itself, at which point the 20 kcal are no longer in excess of demands and a new caloric balance is found (weight-gain plateau – the reverse happens with caloric restriction). Thus, to continue gaining weight, one has to continue increasing caloric intake to ensure that they stay above actual requirements. This self-limiting nature on the effect of a change in caloric intake (increase or decrease) on weight gain is often forgotten when people make simplistic assumptions that small increases in caloric intake have large effects on body weight over time – they don’t! Nevertheless, the lower your caloric requirements, the greater your risk of eating too many calories.

@DrSharma
Edmonton, AB

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There Is More To Obesity Than Just Energy In and Energy Out

Continuing with citations from my article in Obesity Reviews on an aeteological framework for assess obesity, I have the following quote to offer:

In the same manner in which a complete understanding of oedema requires the assessment of the complex physiological systems affecting fluid and sodium homeostasis, understanding obesity requires a comprehensive appreciation of the multitude of factors affecting energy intake and expenditure. Energy expenditure can be further subdivided into non‐activity (= resting metabolic rate + dietary‐induced thermogenesis) and activity thermogenesis (= non‐exercise + exercise activity thermogenesis). For simplicity’s sake, these three elements can be termed diet, metabolism and activity. A change in any one of these elements, if not balanced by corrective changes in the others, will result in a net change in energy balance, which, if positive, will result in caloric ‘retention’ and weight gain.

In subsequent posts, I will discuss the many factors that can affect energy metabolism, food intake, and physical activity and how changes to each (if not balance by corrective changes in the others) can lead to weight gain and often pose barriers to obesity management.

Stay tuned….

@DrSharma
Edmonton, AB

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