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BackgroundBrown adipose tissue (BAT) has emerged as a novel player in energy homeostasis in humans and is considered a potential new target for combating obesity and related diseases. The current 'gold standard' for quantification of BAT volume and activity is cold-induced 18F-FDG uptake in BAT. However, use of this technique is limited by cost and radiation exposure. Given the fact that BAT is a thermogenic tissue, mainly located in the supraclavicular region, the aim of the current study was to investigate whether cold-induced supraclavicular skin temperature and core body temperature may be alternative markers of BAT activation in humans.Subjects/methodsBAT volume and activity were measured in 24 healthy lean adolescent males (mean age 24.1±0.8 years), using cold-induced 18F-FDG uptake with PET-CT. Core body temperature was measured continuously in the small intestine with use of an ingestible telemetric capsule and skin temperature was measured by eighteen wireless iButtons attached to the skin following ISO-defined locations.ResultsProximal and distal (hand/feet) skin temperatures markedly decreased upon cold exposure, while supraclavicular skin temperature significantly increased (35.2±0.1 vs. 35.5±0.1°C, p = 0.001). Furthermore, cold-induced supraclavicular skin temperature positively correlated with both total (R2 = 0.28, P = 0.010) and clavicular BAT volume (R2 = 0.20, P = 0.030) and clavicular SUVmax (R2 = 0.27, P = 0.010), while core body temperature did not.ConclusionsSupraclavicular skin temperature as measured by iButtons may have predictive value for BAT detection in adult humans. This is highly desirable considering the increasing interest in pharmacological interventions to stimulate BAT in human subjects.Trial registrationNTR 2473.

Background/aimsBrown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP-1 and is a promising target to combat hyperlipidemia and obesity. BAT is densely innervated by the sympathetic nervous system, which increases BAT differentiation and activity upon cold exposure. Recently, Bone Morphogenetic Protein 7 (BMP7) was identified as an inducer of BAT differentiation. We aimed to elucidate the role of sympathetic activation in the effect of BMP7 on BAT by treating mice with BMP7 at varying ambient temperature, and assessed the therapeutic potential of BMP7 in combating obesity.Methods and resultsHigh-fat diet fed lean C57Bl6/J mice were treated with BMP7 via subcutaneous osmotic minipumps for 4 weeks at 21 °C or 28 °C, the latter being a thermoneutral temperature in which sympathetic activation of BAT is largely diminished. At 21 °C, BMP7 increased BAT weight, increased the expression of Ucp1, Cd36 and hormone-sensitive lipase in BAT, and increased total energy expenditure. BMP7 treatment markedly increased food intake without affecting physical activity. Despite that, BMP7 diminished white adipose tissue (WAT) mass, accompanied by increased expression of genes related to intracellular lipolysis in WAT. All these effects were blunted at 28 °C. Additionally, BMP7 resulted in extensive 'browning' of WAT, as evidenced by increased expression of BAT markers and the appearance of whole clusters of brown adipocytes via immunohistochemistry, independent of environmental temperature. Treatment of diet-induced obese C57Bl6/J mice with BMP7 led to an improved metabolic phenotype, consisting of a decreased fat mass and liver lipids as well as attenuated dyslipidemia and hyperglycemia.ConclusionTogether, these data show that BMP7-mediated recruitment and activation of BAT only occurs at subthermoneutral temperature, and is thus likely dependent on sympathetic activation of BAT, and that BMP7 may be a promising tool to combat obesity and associated disorders.

BackgroundA physiological model of increased plasma nonesterified fatty acid (NEFA) levels result in myocardial triglyceride (TG) accumulation, which is related to cardiac dysfunction. A pathophysiological model of increased plasma NEFA levels result in hepatic steatosis, which has been linked to abnormal myocardial energy metabolism. Hepatic steatosis is accompanied by hepatic inflammation, reflected by plasma cholesteryl ester transfer protein (CETP) levels. The current study aimed to investigate effects of these models via different nutritional interventions on right ventricular (RV) function.MethodsFifteen men (age 25.0±6.6 years) were included and underwent magnetic resonance imaging and spectroscopy in this prospective crossover intervention study. RV function, myocardial and hepatic TG content, and CETP levels were assessed on three occasions: after normal diet, very low-calorie diet (VLCD, physiological model) and high-fat high-energy (HFHE, pathophysiological model) diet (all 3-days diets, randomly ordered, washout phase at least 14 days).ResultsVLCD induced a decrease in mean E deceleration by 27%. Myocardial TG content increased by 55%, whereas hepatic TG content decreased by 32%. Plasma CETP levels decreased by 14% (all PConclusionsThese findings show that RV diastolic function is impaired after short-term VLCD and HFHE diet in healthy men, respectively a physiological and a pathophysiological model of increased plasma NEFA levels. After short-term VLCD, myocardial lipotoxicity may be of importance in decreased RV diastolic function. RV diastolic dysfunction is accompanied by increased hepatic TG content and plasma CETP levels after short-term HFHE diet, suggesting that systemic inflammation reflecting local macrophage infiltration in the heart may be involved in RV dysfunction.