Diet-induced thermogenesis (DIT) is energy dissipated as heat after a meal, contributing 5–15% to total daily energy expenditure (EE). There has been a long interest in the intriguing possibility that a defect in DIT predisposes to obesity. However, the evidence is conflicting; DIT is usually quantified by indirect calorimetry, which does not measure heat. Using gas exchange, indirect calorimetry measures total post-prandial EE, which comprises heat energy produced from brown adipose tissue (BAT) and energy required for processing and storing nutrients. We questioned whether DIT is reliably quantified by indirect calorimetry by employing infrared thermography to independently assess thermogenesis. Thermogenic activity of BAT was stimulated by cold and by a meal that induced a parallel increase in energy production. These stimulatory effects on BAT thermogenesis were inhibited by glucocorticoids. However, glucocorticoids enhanced postprandial EE in the face of reduced BAT thermogenesis and stimulated lipid synthesis. The increase in EE correlated significantly with the increase in lipogenesis. As energy cannot be destroyed (first law of thermodynamics), the energy that would have been dissipated as heat after a meal is channeled into storage. Post-prandial EE is the sum of heat energy that is lost (true DIT) and chemical energy that is stored. Indirect calorimetry does not reliably quantify DIT. When estimated by indirect calorimetry, assumed DIT can be a friend or foe of energy balance. That gas exchange-derived DIT reflects solely energy dissipation as heat is a false assumption likely to explain the conflicting results on the role of DIT in obesity.
Ken K Y Ho
Advances in clinical chemistry, molecular biology and information technology have brought about major changes in the field of endocrinology. The future practice of endocrinology will be influenced by secular health trends, consumer expectations and the globalisation of health. Pharmacotherapy will remain the backbone of endocrine therapy led by developments in drug delivery technology, pharmacogenomics, combinatorial chemistry and paracrinology. The endocrine-related consequences of obesity and ageing will be major health problems, demand for anti-obesity and anti-ageing treatments will escalate. There will be increased blurring between endocrine disease and non-disease. The future clinical endocrinologist must continue to practice evidence-based medicine to improve the treatment of genuine endocrinopathies.
Johanna L Barclay, Hadiya Agada, Christina Jang, Micheal Ward, Neil Wetzig and Ken K Y Ho
Clinical cases of glucocorticoid (GC) excess are characterized by increased fat mass and obesity through the accumulation of white adipocytes. The effects of GCs on growth and function of brown adipose tissue are unknown and may contribute to the negative energy balance observed clinically. This study aims to evaluate the effect of GCs on proliferation, differentiation, and metabolic function of brown adipocytes. Human brown adipocytes sourced from supraclavicular fat biopsies were grown in culture and differentiated to mature adipocytes. Human white adipocytes sourced from subcutaneous abdominal fat biopsies were cultured as controls. Effects of dexamethasone on growth, differentiation (UCP1, CIDEA, and PPARGC1A expression), and function (oxygen consumption rate (OCR)) of brown adipocytes were quantified. Dexamethasone (1 μM) significantly stimulated the proliferation of brown preadipocytes and reduced that of white preadipocytes. During differentiation, dexamethasone (at 0.1, 1, and 10 μM) stimulated the expression of UCP1, CIDEA, and PPARGC1A in a concentration-dependent manner and enhanced by fourfold to sixfold the OCR of brown adipocytes. Isoprenaline (100 nM) significantly increased (P<0.05) expression of UCP1 and OCR of brown adipocytes. These effects were significantly reduced (P<0.05) by dexamethasone. Thus, we show that dexamethasone stimulates the proliferation, differentiation, and function of human brown adipocytes but inhibits adrenergic stimulation of the functioning of brown adipocytes. We conclude that GCs exert complex effects on development and function of brown adipocytes. These findings provide strong evidence for an effect of GCs on the biology of human brown adipose tissue (BAT) and for the involvement of the BAT system in the metabolic manifestation of Cushing's syndrome.