Article

The brown adipocyte: Update on its metabolic role

Laval University, Quebec City, Quebec, Canada
The International Journal of Biochemistry & Cell Biology (Impact Factor: 4.05). 12/2004; 36(11):2098-104. DOI: 10.1016/j.biocel.2004.04.003
Source: PubMed

ABSTRACT

Brown adipocytes are multilocular lipid storage cells that play a crucial role in non-shivering thermogenesis. These cells are located in brown adipose tissue (BAT) depots which are found in abundance in small mammals as well as in newborns of larger mammals, including humans. Brown adipocytes comprise a very large number of mitochondria packed with cristae and are densely innervated by the sympathetic nervous system (SNS). Sympathetic nerve endings release noradrenaline (NA) in the proximity of brown fat cells, where noradrenaline activates G-protein-coupled beta-adrenergic receptors (AR) and by doing so initiates a cascade of metabolic events culminating in the activation of uncoupling protein 1 (UCP1). Uncoupling protein 1 is a unique feature of brown adipocytes that allows for the generation of heat upon sympathetic nervous system stimulation. It is found in the inner membrane of the mitochondrion, where uncoupling protein 1 uncouples the oxidation of fuel from adenosine triphosphate (ATP) production. The expression of uncoupling protein 1 is strongly induced by cold exposure, revealing the importance of this uncoupling protein in thermoregulation. The thermoregulatory role of uncoupling protein 1 has been emphasized in uncoupling protein 1-deficient mice, whose resistance to cold is impaired. Uncoupling protein 1 expression is modulated by diet and metabolic hormones such as leptin and glucocorticoids, which suggests that the protein is a player in energy balance regulation.

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    • "In both tissues uncoupling proteins (UCP), localized at the inner mitochondrial membrane, are responsible for heat dissipation. UCP1 is the most prominent protein of this family and is limited to BAT (Sell et al., 2004). UCP1 is primarily activated by noradrenergic stimulation mediated by the SNS, but T3 is involved as coactivator and is essential for the full thermogenic response of BAT (Bianco and Silva, 1987; Silva and Larsen, 1986). "

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    • "In both tissues uncoupling proteins (UCP), localized at the inner mitochondrial membrane, are responsible for heat dissipation. UCP1 is the most prominent protein of this family and is limited to BAT (Sell et al., 2004). UCP1 is primarily activated by noradrenergic stimulation mediated by the SNS, but T3 is involved as coactivator and is essential for the full thermogenic response of BAT (Bianco and Silva, 1987; Silva and Larsen, 1986). "
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    ABSTRACT: Thyroid hormones (TH) play a key role in regulation of seasonal as well as acute changes in metabolism. Djungarian hamsters (Phodopus sungorus) adapt to winter by multiple changes in behaviour and physiology including spontaneous daily torpor, a state of hypometabolism and hypothermia. We investigated effects of systemic TH administration and ablation on the torpor behaviour in Djungarian hamsters adapted to short photoperiod. Hyperthyroidism was induced by giving T4 or T3 and hypothyroidism by giving methimazole (MMI) and sodium perchlorate via drinking water. T3 treatment increased water, food intake and body mass, whereas MMI had the opposite effect. Continuous recording of body temperature revealed that low T3 serum concentrations increased torpor incidence, lowered Tb and duration, whereas high T3 serum concentrations inhibited torpor expression. Gene expression of deiodinases (dio) and uncoupling proteins (ucp) were analysed by qPCR in hypothalamus, brown adipose tissue (BAT) and skeletal muscle. Expression of dio2, the enzyme generating T3 by deiodination of T4, and ucps, involved in thermoregulation, indicated a tissue specific response to treatment. Torpor per se decreased dio2 expression irrespective of treatment or tissue, suggesting low intracellular T3 concentrations during torpor. Down regulation of ucp1 and ucp3 during torpor might be a factor for the inhibition of BAT thermogenesis. Hypothalamic gene expression of neuropeptide Y, propopiomelanocortin and somatostatin, involved in feeding behaviour and energy balance, were not affected by treatment. Taken together our data indicate a strong effect of thyroid hormones on torpor, suggesting that lowered intracellular T3 concentrations in peripheral tissues promote torpor.
    No preview · Article · Oct 2015 · Hormones and Behavior
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    • "WAT is the primary site of energy storage in the form of triglycerides, whereas BAT contains multilocular adipocytes which contains a large number of mitochondria and plays a substantial role in non-shivering thermogenesis [5]. Sympathetic nerve endings release noradrenaline in the proximity of brown fat cells, where noradrenaline activates G-protein-coupled β-adrenergic receptors initiating a cascade of metabolic events resulting in the activation of uncoupling protein 1 (UCP1) [6]. Insulin antagonizes hormone-induced lipolysis -caused by counter-regulatory hormones e.g. "
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    ABSTRACT: Introduction: T2DM is a group of metabolic disorders manifested by hyperglycemia as a result of insulin insufficiency and/or resistance. The main goal of antidiabetic therapies is to lower glucose levels, and therefore prevent development of diabetes complications. DPP-4 inhibitors (e.g. sitagliptin) are relatively new antidiabetic drugs which inhibit the activity of DPP-4 enzyme and therefore prevent rapid degradation of incretin hormones. Objective: We investigated effects of sitagliptin on glucose homeostasis, lipid profile, and insulin signaling by determination of cAMP levels in peripheral tissues of HFD/STZ diabetic rats, compared to glimepiride. Methods: The experimental rats were divided into five groups, each group comprising 10 rats. Group (1) served as the normal control rats and administered DMSO (without treatments) as the vehicle. The rest of the groups were rendered diabetic by feeding HFD containing 40% fats for 4 weeks, followed by a single I.P. injection of STZ (45 mg/kg of body weight). One week after STZ injection, the rats with FBG level of ≥ 200 mg/dl were considered diabetic. Group (2) served as the diabetic untreated rats and administered DMSO (without treatments) as the vehicle. Group (3) served as diabetic rats treated with glimepiride (0.1 mg/kg of body weight). Group (4) and group (5) served as diabetic rats treated with sitagliptin (10 and 30 mg/kg of body weight, respectively). Treatments were dissolved in DMSO and were given orally for 4 weeks. At the end of the treatment period, the blood, liver and adipose tissues (White and brown) were collected for biochemical analysis. Results: In normal control rats, the highest content of cAMP was observed in BAT. Diabetic rats showed an elevation in cAMP levels of liver and WAT to be 1.3 and 3.9 fold control values, respectively, while in BAT, cAMP level decreased to be 0.4 fold control value. Sitagliptin and glimepiride significantly decreased cAMP levels in liver and WAT. Conclusion: We conclude that sitagliptin and glimepiride have comparable effects on glucose homeostasis. Both drugs have cAMP-lowering effect which may suggest their potential protecting effect against vascular complications of diabetes.
    Full-text · Article · Sep 2014
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