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


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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Available from: Henrike Sell, Oct 02, 2015
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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.
    09/2014; 2(3):52-60. DOI:10.12691/ajbr-2-3-3
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    • "Acyl-carnitine is converted back to acyl-CoA, which can then enter the fatty acid β-oxidation pathway. Free fatty acids not only act as substrates for β-oxidation but also stimulate UCP1 activity [17,19]. The expressions of CPT1 mRNA and protein were not significantly different between HF mice and HFM mice in our study (Figure  6A, B), which suggests that the β-oxidation activity was similar in the two groups. "
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    ABSTRACT: Miglitol is an oral anti-diabetic drug that acts by inhibiting carbohydrate absorption in the small intestine. Recent studies have shown that miglitol reduces obesity in humans and rodents. However, its mechanisms have remained unclear. The purpose of this study was to determine whether miglitol generates heat by activating uncoupling protein 1 (UCP1), an enzyme involved in thermogenesis, in brown adipose tissue (BAT) in mice. Four-week-old male C57BL/6 J mice were fed a high-fat diet alone (HF) or a high fat diet plus miglitol (HFM). Oxygen consumption (VO2) was used to estimate metabolic rate. A thermal imaging camera was used to quantify heat generation from interscapular brown adipose tissue. We analyzed the protein and gene expressions of UCP1 and the expressions of four proteins related to beta3-adrenergic signaling in the pathway activating UCP1 (protein kinase A (PKA), hormone-sensitive lipase (HSL), p38 alpha mitogen-activated protein kinase (p38alphaMAPK) and peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC1alpha)). At 8 weeks, body weight, epididymal and subcutaneous white adipose tissue and the HOMA-R value of the HFM mice were significantly less than those of the HF mice. Food intake was not different between the HF and HFM mice. VO2 and BAT temperature were significantly higher in the HFM mice. Miglitol significantly enhanced the gene and protein expressions of UCP1 and the expressions of proteins related to beta3-adrenergic signaling. Miglitol's anti-obesity effect was attributed to increased energy expenditure by upregulating UCP1 in BAT (i.e., by thermogenesis) and to enhancement of beta3-adrenergic signaling in BAT.
    Nutrition & Metabolism 03/2014; 11(1):14. DOI:10.1186/1743-7075-11-14 · 3.26 Impact Factor
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    • "Brown adipocytes are characterized by multilocular lipid droplets and a high density of mitochondria, which contain uncoupling protein 1 (UCP1). UCP1 is located in the inner membrane of the mitochondria and uncouples substrate oxidation from adenosine triphosphate (ATP) synthesis, thereby providing the BAT capacity for nonshivering thermogenesis by dissipating energy as heat instead of generating ATP.188 "
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    ABSTRACT: Obesity is a global epidemic associated with aging-like cellular processes; in both aging and obesity, resistance to hormones such as insulin and leptin can be observed. Leptin is a circulating hormone/cytokine with central and peripheral effects that is released mainly by subcutaneous white adipose tissue. Centrally, leptin controls food intake, energy expenditure, and fat distribution, whereas it controls (among several others) insulin sensitivity, free fatty acids (FFAs) oxidation, and lipolysis in the periphery. Aging is associated with important changes in both the distribution and the composition of adipose tissue. Fat is redistributed from the subcutaneous to the visceral depot and increased inflammation participates in adipocyte dysfunction. This redistribution of adipose tissue in favor of visceral fat influences negatively both longevity and healthy aging as shown in numerous animal models. These modifications observed during aging are also associated with leptin resistance. This resistance blunts normal central and peripheral functions of leptin, which leads to a decrease in neuroendocrine function and insulin sensitivity, an imbalance in energy regulation, and disturbances in lipid metabolism. Here, we review how age-related leptin resistance triggers metabolic disturbances and affects the longevity of obese patients. Furthermore, we discuss the potential impacts of leptin resistance on the decline of brown adipose tissue thermogenesis observed in elderly individuals.
    Clinical Interventions in Aging 07/2013; 8:829-44. DOI:10.2147/CIA.S36367 · 2.08 Impact Factor
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