Thermogenic mechanisms in brown fat.

Nicholls, David G.; Locke, Rebecca M.

doi:10.1152/physrev.1984.64.1.1

Cited by 1,511 publications

(944 citation statements)

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“…Brown and white adipocytes are usually located in distinct depots and can be distinguished morphologically [23]; brown adipocytes contain multilocular lipid vacuoles and numerous mitochondria, whereas white adipocytes have a unilocular lipid vacuole and few mitochondria. UCP-1 is specifically produced in BAT; this protein uncouples oxidative phosphorylation from electron transport, resulting in the dissipation of energy as heat [24,25]. The emergence of these ectopic cells in the WAT of rats [26] and of mice [27] was found to be induced by cold acclimatisation or by the administration of selective β3-AR agonists [27,28].…”

Section: Introductionmentioning

confidence: 99%

Increased fat:carbohydrate oxidation ratio in Il1ra −/− mice on a high-fat diet is associated with increased sympathetic tone

et al. 2008

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Aims/hypothesis Proinflammatory cytokines, including IL-1, exert pleiotropic effects on the neuro-immuno-endocrine system. Previously, we showed that mice with knockout of the gene encoding IL-1 receptor antagonist (Il1ra −/− , also known as Il1rn −/− ) have a lean phenotype. The present study was designed to analyse the mechanisms leading to this lean phenotype.Methods Il1ra −/− mice were fed a high-fat diet following weaning. Energy expenditure, body temperature, heart rate, blood parameters, urinary catecholamines and adipose tissue were analysed. Results Il1ra −/− mice exhibited resistance to obesity induced by a high-fat diet; this resistance was associated with increased energy expenditure and a decreased respiratory quotient, indicating that the ratio of fat:carbohydrate metabolism in Il1ra −/− mice is greater than in controls. Activity level in Il1ra −/− mice was significantly decreased and body temperature was significantly increased, compared with wild-type (WT) mice. Inguinal white adipose tissues in Il1ra −/− mice express increased levels of Ucp1 and mitochondrial respiratory chain genes compared with WT mice. Histological analysis of adipose tissue in Il1ra −/− mice revealed that brown adipose tissue is hyperactive and inguinal white adipose tissue contains smaller cells, which exhibit the distinctive multilocular appearance of brown adipocytes. Urinary epinephrine and norepinephrine excretion in Il1ra −/− mice was significantly increased compared with WT mice, suggesting that Il1ra −/− mice have increased sympathetic tone. Consistent with this, heart rate in Il1ra −/− mice was also significantly increased. Conclusions/interpretation Our results show that Il1ra −/− mice have increased energy expenditure, fat:carbohydrate oxidation ratio, body temperature, heart rate and catecholamine production. All of these observations are consistent with an enhanced sympathetic tone.

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Section: Introductionmentioning

confidence: 99%

Increased fat:carbohydrate oxidation ratio in Il1ra −/− mice on a high-fat diet is associated with increased sympathetic tone

et al. 2008

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“…Brown adipose tissue (BAT), the major site of nonshivering thermogenesis in newborn and coldacclimated animals (for review see [1]) contains, similarly to the brain, pituitary and pineal gland, type II iodothyronine 5'-deiodinase (5'D) [2]. In contrast to type I enzyme present in liver and kidney, type II 5'D is insensitive to propylthiouracil, exhibits different kinetics and has low gm values for T4 and reverse T3 in the nanomolar range [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…The local production of T3 by 5'D in BAT in concurrence with norepinephrine [13,14] is essential for the synthesis of mitochondrial uncoupling protein (UCP), the key and rate-limiting component of BAT thermogenesis [1,15]. When fully activated, 5'D of BAT represents a substantial source of systemic T3, in hypothyroid animals in particular [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Induction of type II iodothyronine 5'‐deiodmase and mitochondrial uncoupling protein in brown adipocytes differentiated in cell culture

et al. 1990

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Brown adipocytes differentiated in primary cell culture were found to contain a type II iodothyronine 5'‐deiodinase (5'D), Incubation of confluent cells with norepinephrine or dibutyryl‐cAMP caused up to 17‐fold increase in 5'D activity with a maximum after 8 h. Activation of 5'D required mRNA and protein synthesis and was accompanied by parallel, up to 5.8‐fold increase in the amount of mitochondrial uncoupling protein with a maximum after 24 h. Analysis ofadrenergic stimulation of 5'D suggested predominant involvement of the β‐receptors and increased intracellular cAMP levels, while the contribution of x1,‐receptors was small.

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“…Increased heat production is achieved by allowing proton re-entry into the mitochondrial matrix, via an alternative pathway to that associated with ATP synthesis. Thus, respiration rate, no longer determined by the cell's requirement for ATP, proceeds at an unrestrained rate (for review, see Nicholls & Locke, 1984). This loose coupling of BAT mitochondria has been attributed to a unique Mr-32000 protein, in the mitochondrial inner membrane, known as 'thermogenin' or 'uncoupling protein' (Heaton et al, 1978).…”

Section: Introductionmentioning

confidence: 99%

“…This loose coupling of BAT mitochondria has been attributed to a unique Mr-32000 protein, in the mitochondrial inner membrane, known as 'thermogenin' or 'uncoupling protein' (Heaton et al, 1978). The protein is thought to be a proton conductance channel (Klingenberg & Winkler, 1985), which can be inhibited by a purine nucleotide binding to a site exposed on the outer surface of the mitochondrial inner membrane (Nicholls & Locke, 1984). The specific binding of [3H]GDP has been used extensively as an indication of the thermogenic state of the tissue.…”

Section: Introductionmentioning

confidence: 99%

Regulation of GDP binding and uncoupling-protein concentration in brown-adipose-tissue mitochondria. The effects of cold-acclimation, warm-reacclimation and noradrenaline

Peachey

French

York

1988

Biochemical Journal

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We have used a specific immunoassay for uncoupling protein and [3H]GDP binding to study the acute and chronic responses of brown-adipose-tissue (BAT) mitochondria of warm-acclimated rats to housing at 4°C and cold-acclimated rats to housing at 27 'C. These studies have shown the following. (1) In the coldexposed rat the increase in mitochondrial uncoupling-protein concentration parallels the increase in GDP binding from 1 day to 5 days, but that acutely (initial 4 h) the increase in GDP binding is not associated with any change in uncoupling-protein concentration. 2. In the cold-acclimated rat rehoused at 27 'C, GDP binding fell by over 50 % in the first 2 days, without any change in uncoupling-protein concentrations. 3. Noradrenaline acutely (30 min) increased BAT mitochondrial GDP binding of lean and obese Zucker rats, without any change in uncoupling-protein concentrations. 4. The increases in GDP binding in cold-exposed rats were associated with increases in the rate of swelling of mitochondria in the presence of valinomycin and potassium acetate. The evidence supports the hypothesis that the acute response of the rat to changes in environmental temperature are associated with unmasking or remasking of uncoupling protein, whereas chronically changes in uncoupling-protein concentration predominate.

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Thermogenic mechanisms in brown fat.

Cited by 1,511 publications

References 0 publications

Increased fat:carbohydrate oxidation ratio in Il1ra −/− mice on a high-fat diet is associated with increased sympathetic tone

Increased fat:carbohydrate oxidation ratio in Il1ra −/− mice on a high-fat diet is associated with increased sympathetic tone

Induction of type II iodothyronine 5'‐deiodmase and mitochondrial uncoupling protein in brown adipocytes differentiated in cell culture

Regulation of GDP binding and uncoupling-protein concentration in brown-adipose-tissue mitochondria. The effects of cold-acclimation, warm-reacclimation and noradrenaline

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