Disparate effects of fenfluramine on thermogenesis in brown adipose tissue in the rat

1992 ◽  
Vol 70 (2) ◽  
pp. 214-218 ◽  
Author(s):  
Stephanie W. Y. Ma ◽  
Edward Preston
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Ambient Temperature ◽  
Brown Adipose Tissue ◽  
Metabolic Effects ◽  
Whole Body ◽  
Flow Measurements ◽  
Brown Adipose ◽  
Cardiac Ventricle ◽  
Blood Flow Measurements

It has been suggested that fenfluramine, a clinically used appetite suppressant, can also promote weight loss by augmenting energy expenditure, as indicated by increased whole-body O2 consumption [Formula: see text] and mitochondrial GDP binding in brown adipose tissue (BAT) of fenfluramine-treated rats. To further investigate a possible involvement of BAT in the drug's metabolic effects, 113Sn-labelled microspheres were injected into the left cardiac ventricle of conscious rats 70–80 min after intraperitoneal delivery of 20 mg/kg fenfluramine (DL-mixture) or saline vehicle. At 28 °C ambient temperature, fenfluramine augmented resting whole-body [Formula: see text] and increased the microsphere entrapment in BAT, indicating enhanced blood flow and metabolism. At 20 °C ambient temperature, the expected increase in BAT blood flow associated with nonshivering thermogenesis was observed in control rats, but in fenfluramine-treated rats the increase in BAT blood flow was severely attenuated, and [Formula: see text] and body temperature were reduced. The stimulatory effect of fenfluramine on BAT metabolism was not prevented by urethane anesthesia but did not occur if the tissue was denervated. These blood flow measurements corroborate previous reports, based on GDP-binding assays, that fenfluramine treatment can augment thermogenesis in BAT by effects mediated through the innervation of the tissue. However, the data also indicate that this calorigenic effect is dependent on ambient temperature being near thermoneutrality and that in a cool environment the drug inhibits BAT thermogenesis.Key words: fenfluramine, brown adipose tissue, thermogenesis.

Differences between the effects of noradrenaline and the β-adrenoceptor agonist BRL 28410 in brown adipose tissue and hind limb of the anaesthetized rat

1986 ◽  
Vol 64 (8) ◽  
pp. 1111-1114 ◽  
Author(s):  
Peter L. Thurlby ◽  
Rodney D. M. Ellis
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Oxygen Uptake ◽  
Brown Adipose Tissue ◽  
Oxygen Delivery ◽  
Hind Limb ◽  
Oxygen Extraction ◽  
Whole Body ◽  
Adrenoceptor Agonist ◽  
Brown Adipose

In mature (450–600 g) 21 °C-acclimated male rats, anaesthetized with urethane, blood flow (measured by the radioactive microsphere technique) to brown adipose tissue (BAT) was determined during the infusion of the β-adrenoceptor agonist BRL 28410 or noradrenaline bitartrate at doses chosen to give similar increases in whole body oxygen uptake. Blood flow to BAT during BRL 28410 infusion was only about one third of that found during noradrenaline infusion although increases in whole body thermogenesis were similar (55 and 77% for BRL 28410 and noradrenaline, respectively). This suggests that BAT may be less involved in the thermogenic response to BRL 28410 than to noradrenaline. In a separate experiment using slightly smaller rats (350–500 g) hind limb oxygen uptake was measured in situ using a venous bypass preparation. BRL 28410, at a dose having a maximum effect on whole body thermogenesis (53% increase), had no effect on oxygen delivery to the hind limb but significantly increased oxygen extraction by 33% (p < 0.001). In contrast, noradrenaline, also at a dose that maximally increased whole body thermogenesis, led to a 35% decrease in oxygen delivery to the hind limb and no change in oxygen extraction. For the thermogenic β-agonist BRL 28410 the hind limb, and presumably muscular tissue in general, may be contributing to thermogenesis.

Brown adipose tissue, liver, and diet-induced thermogenesis in cafeteria diet-fed rats

1989 ◽  
Vol 67 (4) ◽  
pp. 376-381 ◽  
Author(s):  
Stephanie W. Y. Ma ◽  
David O. Foster
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Direct Determination ◽  
Metabolizable Energy ◽  
Whole Body ◽  
Tissue Blood Flow ◽  
Direct Measurements ◽  
Brown Adipose ◽  
Diet Induced Thermogenesis

Diet-induced thermogenesis (DIT) in young rats overeating a "cafeteria" (CAF) diet of palatable human foods is characterized by a chronic, propranolol-inhibitable elevation in resting metabolic rate [Formula: see text] and is associated with various changes in brown adipose tissue (BAT) that have been taken as evidence for BAT as the effector of DIT. But direct evidence for participation of BAT in DIT has been lacking. By employing a nonocclusive cannula to sample the venous effluent of interscapular BAT (IBAT) for analysis of its O2 content and measuring tissue blood flow with microspheres, we accomplished direct determination (Fick principle) of the O2 consumption of BAT in conscious CAF rats. In comparison with normophagic controls fed chow, the CAF rats exhibited a 43% increase in metabolizable energy intake, reduced food efficiency, a 22% elevation in resting [Formula: see text] at 28 °C (thermoneutrality) or 24 °C (housing temperature), and characteristic changes in the properties of their BAT (e.g., increased mass, protein content and mitochondrial GDP binding). They also exhibited the greater metabolic response to exogenous noradrenaline characteristic of CAF rats and the near elimination by propranolol of their elevation in [Formula: see text]. By the criterion of their elevated [Formula: see text], the CAF rats were exhibiting DIT at the time of the measurements of BAT blood flow and blood O2 levels. However, BAT O2 consumption was found to be no greater in the CAF rats than in the controls at either 28 or 24 °C. At 28 °C it accounted for less than 1% of whole body [Formula: see text]; at 24 °C it increased to about 10% of overall [Formula: see text] in both diet groups. Direct measurements of BAT O2 consumption during expression of the thermic response to a tube-fed meal were also made in conscious CAF and control rats. Both diet groups exhibited an approximately 15% increase in whole body [Formula: see text] at 90–120 min after the meal. The contribution by BAT to this increase was only 2–3% and did not differ significantly between groups. Thus, the results of these direct measurements of BAT O2 consumption in vivo do not support the theory that DIT in CAF rats is mainly due to increased BAT thermogenesis occurring either chronically or during assimilation of a meal. In further studies of the effector(s) of DIT in CAF rats, partial hepatectomy (two-thirds of the liver removed) was found to acutely reduce the resting [Formula: see text] of CAF rats by 1.85 mL/min, 2.3 times as much as in chow-fed controls. From this difference in response, it was estimated that in the CAF rats liver O2 consumption before hepatectomy exceeded that of the controls by about 1.5 mL/min, an amount that would be sufficient to fully account for the elevation in resting [Formula: see text] of the former. A major role for the liver in the DIT of CAF rats is thus suggested.Key words: cafeteria feeding, diet-induced thermogenesis, thermic effect of food, brown fat, liver.

scholarly journals Melatonin increases brown adipose tissue acute thermogenic capacity in rats measured by 18F-FDG PET

2020 ◽  
Author(s):  
Bruno Halpern ◽  
Marcio C Mancini ◽  
Caroline Mendes ◽  
Camila Maria Longo Machado ◽  
Silvana Prando ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Ambient Temperature ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Fdg Pet ◽  
Metabolic Effects ◽  
Bat Activity ◽  
Acute Cold Exposure ◽  
Brown Adipose ◽  
Thermogenic Capacity

Abstract Objective Melatonin has been shown to increase brown adipose tissue (BAT) mass, which can lead to important metabolic effects, as bodyweight reduction and glycemic improvement. However, BAT mass can only be measured invasiveness, and the gold-standard for non-invasive measurement of BAT activity is positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose ( 18 F-FDG PET). There is no study, to our knowledge that evaluated if melatonin influences BAT activity measured by this imaging technique. Methods Three experimental groups (control, pinealectomy, and pinealectomy replaced ith melatonin) performed 18 F-FDG PET in ambient temperature and after acute cold exposure. The ratio of increased BAT activity after cold exposure/ambient temperature was called “acute thermogenic capacity.” We also measured UCP-1 mRNA expression to correlate with 18 F-FDG PET results. Results Pinealectomy led to a reduced acute thermogenic capacity compared with the other groups, as well as a reduced UCP1 mRNA expression.Conclusion Melatonin deficiency apparently impairs BAT response to acute cold exposure. These results can lead to future studies of the influence of melatonin on BAT, in animals and humans, without the need for invasive evaluation of BAT.

scholarly journals The Role of AMPK Signaling in Brown Adipose Tissue Activation

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1122
Author(s):  
Jamie I. van der van der Vaart ◽  
Mariëtte R. Boon ◽  
Riekelt H. Houtkooper
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Whole Body ◽  
Ampk Signaling ◽  
Mitochondrial Homeostasis ◽  
Brown Adipose ◽  
Metabolic Stresses ◽  
Amp Activated Protein Kinase ◽  
Body Energy

Obesity is becoming a pandemic, and its prevalence is still increasing. Considering that obesity increases the risk of developing cardiometabolic diseases, research efforts are focusing on new ways to combat obesity. Brown adipose tissue (BAT) has emerged as a possible target to achieve this for its functional role in energy expenditure by means of increasing thermogenesis. An important metabolic sensor and regulator of whole-body energy balance is AMP-activated protein kinase (AMPK), and its role in energy metabolism is evident. This review highlights the mechanisms of BAT activation and investigates how AMPK can be used as a target for BAT activation. We review compounds and other factors that are able to activate AMPK and further discuss the therapeutic use of AMPK in BAT activation. Extensive research shows that AMPK can be activated by a number of different kinases, such as LKB1, CaMKK, but also small molecules, hormones, and metabolic stresses. AMPK is able to activate BAT by inducing adipogenesis, maintaining mitochondrial homeostasis and inducing browning in white adipose tissue. We conclude that, despite encouraging results, many uncertainties should be clarified before AMPK can be posed as a target for anti-obesity treatment via BAT activation.

KCTD10 regulates brown adipose tissue thermogenesis and metabolic function via Notch Signaling

2021 ◽  
Author(s):  
Mingsheng Ye ◽  
Liping Luo ◽  
Qi Guo ◽  
Guanghua Lei ◽  
Chao Zeng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Notch Signaling ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Notch Signaling Pathway ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Metabolic Function ◽  
Brown Adipose

Brown adipose tissue (BAT) is emerging as a target to beat obesity through the dissipation of chemical energy to heat. However, the molecular mechanisms of brown adipocyte thermogenesis remain to be further elucidated. Here, we show that KCTD10, a member of the polymerase delta-interacting protein 1 (PDIP1) family, was reduced in BAT by cold stress and a β3 adrenoceptor agonist. Moreover, KCTD10 level increased in the BAT of obese mice, and KCTD10 overexpression attenuates uncoupling protein 1 (UCP1) expression in primary brown adipocytes. BAT-specific KCTD10 knockdown mice had increased thermogenesis and cold tolerance protecting from high fat diet (HFD)-induced obesity. Conversely, overexpression of KCTD10 in BAT caused reduced thermogenesis, cold intolerance, and obesity. Mechanistically, inhibiting Notch signaling restored the KCTD10 overexpression suppressed thermogenesis. Our study presents that KCTD10 serves as an upstream regulator of notch signaling pathway to regulate BAT thermogenesis and whole-body metabolic function.

scholarly journals Brown Adipose Tissue Activation by Cold Treatment Ameliorates Polycystic Ovary Syndrome in Rat

2021 ◽  
Vol 12 ◽  
Author(s):  
Rongcai Ye ◽  
Chunlong Yan ◽  
Huiqiao Zhou ◽  
Yuanyuan Huang ◽  
Meng Dong ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
Brown Adipose Tissue ◽  
Therapeutic Strategy ◽  
Polycystic Ovary ◽  
Cold Treatment ◽  
Whole Body ◽  
Ovary Syndrome ◽  
Bat Activity ◽  
Brown Adipose

Polycystic ovary syndrome (PCOS) is a common endocrine disease accompanied by energetic metabolic imbalance. Because the etiology of PCOS is complex and remains unclear, there is no effective and specific treatment for PCOS. It is often accompanied by various metabolic disorders such as obesity, insulin resistances, and others. Activated brown adipose tissue (BAT) consumes excess energy via thermogenesis, which has positive effects on energy metabolism. Our previous research and that of others indicates that BAT activity is decreased in PCOS patients, and exogenous BAT transplantation can improve PCOS rodents. Notably however, it is difficult to apply this therapeutic strategy in clinical practice. Therapeutic strategies of enhancing endogenous BAT activity and restoring whole-body endocrine homeostasis may be more meaningful for PCOS treatment. In the current study, the dehydroepiandrosterone-induced PCOS rat was exposed to low temperature for 20 days. The results show that cold treatment could reverse acyclicity of the estrous cycle and reduce circulating testosterone and luteinizing hormone in PCOS rats by activating endogenous BAT. It also significantly reduced the expression of steroidogenic enzymes as well as inflammatory factors in the ovaries of PCOS rats. Histological investigations revealed that cold treatment could significantly reduce ovary cystic follicles and increase corpus luteum, indicating that ovulation was recovered to a normal level. Concordant with these results, cold treatment also improved fertility in PCOS rats. Collectively, these findings suggest that cold treatment could be a novel therapeutic strategy for PCOS.

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