Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in ...glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT(+)) men and five BAT-negative (BAT(-)) men under thermoneutral conditions and after prolonged (5-8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT(+) group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans.
Recent studies suggest that brown adipose tissue (BAT) plays a role in energy and glucose metabolism in humans. However, the physiological significance of human BAT in lipid metabolism remains ...unknown. We studied 16 overweight/obese men during prolonged, non-shivering cold and thermoneutral conditions using stable isotopic tracer methodologies in conjunction with hyperinsulinemic-euglycemic clamps and BAT and white adipose tissue (WAT) biopsies. BAT volume was significantly associated with increased whole-body lipolysis, triglyceride-free fatty acid (FFA) cycling, FFA oxidation, and adipose tissue insulin sensitivity. Functional analysis of BAT and WAT demonstrated the greater thermogenic capacity of BAT compared to WAT, while molecular analysis revealed a cold-induced upregulation of genes involved in lipid metabolism only in BAT. The accelerated mobilization and oxidation of lipids upon BAT activation supports a putative role for BAT in the regulation of lipid metabolism in humans.
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•BAT activation is associated with accelerated lipid metabolism•Cold induced the expression of genes involved in lipid metabolism in BAT•BAT mitochondrial thermogenesis is 45-fold greater than that of WAT•Cold leads to a delayed decrease in TG and VLDL levels
Chondronikola et al. explore the role of BAT in lipid metabolism in humans and show that cold-induced BAT activation is associated with increased whole-body lipolysis, triglyceride-free fatty acid (FFA) cycling, FFA oxidation, and adipose tissue insulin sensitivity. Cold upregulates the expression of genes involved in lipid metabolism specifically in BAT.
Brown adipose tissue (BAT) plays an important role in mammalian thermoregulation. The component of BAT mitochondria that permits this function is the inner membrane carrier protein uncoupling protein ...1 (UCP1). To the best of our knowledge, no studies have directly quantified UCP1 function in human BAT. Further, whether human and rodent BAT have comparable thermogenic function remains unknown. We employed high-resolution respirometry to determine the respiratory capacity, coupling control, and, most importantly, UCP1 function of human supraclavicular BAT and rodent interscapular BAT. Human BAT was sensitive to the purine nucleotide GDP, providing the first direct evidence that human BAT mitochondria have thermogenically functional UCP1. Further, our data demonstrate that human and rodent BAT have similar UCP1 function per mitochondrion. These data indicate that human and rodent BAT are qualitatively similar in terms of UCP1 function.
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•Human BAT has a respiratory capacity 50- to 100-fold greater than that of WAT•Human BAT has functional UCP1•Per mitochondrion, UCP1 function is similar in human and rodent BAT•BAT and skeletal muscle have similar respiratory capacities in humans
Using a PET-CT-guided biopsy technique, Porter et al. provide a detailed analysis of brown adipose tissue (BAT) function, and they show that human BAT has a respiratory capacity 50-fold greater than white fat. Per mitochondrion, UCP1 function is similar between human and rodent BAT, highlighting the thermogenic potential of human BAT.
Brown adipose tissue (BAT) plays an important role in thermoregulation in rodents. Its role in temperature homeostasis in people is less studied. To this end, we recruited 18 men 8 subjects with ...no/minimal BAT activity (BAT-) and 10 with pronounced BAT activity (BAT+). Each volunteer participated in a 6 h, individualized, non-shivering cold exposure protocol. BAT was quantified using positron emission tomography/computed tomography. Body core and skin temperatures were measured using a telemetric pill and wireless thermistors, respectively. Core body temperature decreased during cold exposure in the BAT- group only (-0.34°C, 95% CI: -0.6 to -0.1, p = 0.03), while the cold-induced change in core temperature was significantly different between BAT+ and BAT- subjects (BAT+ vs. BAT-, 0.43°C, 95% CI: 0.20-0.65, p = 0.0014). BAT volume was associated with the cold-induced change in core temperature (p = 0.01) even after adjustment for age and adiposity. Compared to the BAT- group, BAT+ subjects tolerated a lower ambient temperature (BAT-: 20.6 ± 0.3°C vs. BAT+: 19.8 ± 0.3°C, p = 0.035) without shivering. The cold-induced change in core temperature (r = 0.79, p = 0.001) and supraclavicular temperature (r = 0.58, p = 0.014) correlated with BAT volume, suggesting that these non-invasive measures can be potentially used as surrogate markers of BAT when other methods to detect BAT are not available or their use is not warranted. These results demonstrate a physiologically significant role for BAT in thermoregulation in people. This trial has been registered with Clinaltrials.gov: NCT01791114 (https://clinicaltrials.gov/ct2/show/NCT01791114).
Brown adipose tissue (BAT) has been proposed as a potential target tissue against obesity and its related metabolic complications. Although the molecular and functional characteristics of BAT have ...been intensively studied in rodents, only a few studies have used human BAT specimens due to the difficulty of sampling human BAT deposits. We established a novel positron emission tomography and computed tomography-guided Bergström needle biopsy technique to acquire human BAT specimens from the supraclavicular area in human subjects. Forty-three biopsies were performed on 23 participants. The procedure was tolerated well by the majority of participants. No major complications were noted. Numbness (9.6%) and hematoma (2.3%) were the two minor complications noted, which fully resolved. Thus, the proposed biopsy technique can be considered safe with only minimal risk of adverse events. Adoption of the proposed method is expected to increase the sampling of the supraclavicular BAT depot for research purposes so as to augment the scientific knowledge of the biology of human BAT.
Despite intense scientific interest regarding the role of human brown adipose tissue (BAT) in substrate metabolism, its role in whole‐body lipid metabolism remains unclear. To address this issue, we ...studied otherwise matched men with high (HBAT, n=7) and low (LBAT: n=5) BAT volume (69±18 mL vs. 4±2 mL, p<0.05) under cold exposure (CE) and thermoneutral (TN) conditions using positron emission tomography‐computed tomography, stable isotope infusions, and indirect calorimetry. For HBAT, but not LBAT participants, plasma free fatty acid concentrations (TN: 0.36±0.01mmol/L vs. CE: 0.63±0.01mmol/L, p<0.05), plasma glycerol concentrations (TN: 0.05±0.01 mmol/L vs. CE: 0.09±0.01 mmol/L, p<0.05), lipolysis (TN: 2.2±0.3 μmol/kg/min vs. CE: 5.9±0.6μmol/kg/min, p<0.05), and plasma free fatty acid oxidation (TN: 2.7±0.6 μmol/kg/min vs. CE: 5.9±1.0 μmol/kg/min, p<0.05) were higher under CE conditions than TN conditions. Moreover, during CE, plasma small LDL and large HDL particles increased more in the HBAT group than in the LBAT group (p<0.05). Finally, the HBAT group tended to have decreased plasma triglyceride concentrations the day after CE (‐33.4±11.4 mg/dl, p=0.06), whereas LBAT subjects showed no significant change. These novel findings demonstrate a functional role of BAT in human lipid metabolism.
Grant Funding Source: : CTSA UL1TR000071, Pepper Center Pilot Grant, Sealy Center on Aging, Shriners Hospitals
Drug eluting beads on cytology smears Manglik, Niti; Annamalai, Palam; Nawgiri, Ranjana S
Cyto journal/CytoJournal,
2012, Letnik:
9, Številka:
1
Journal Article
Odprti dostop
Transarterial chemoembolization (TACE) is the most widely used primary treatment for unresectable hepatocellular carcinoma (HCC). TACE increases the in-situ dwell time and concentration of drug ...through vascular occlusion by drug-eluting beads (DEB). DEB consist of injectable polymeric microspheres of calibrated size that can be loaded with various antineoplastic solutions.
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