UCP1-independent Thermogenesis in White Adipose Tissue of Cold-acclimated<i>Ucp1</i><sup>-/-</sup>Mice

Ukropec, Jozef; Anunciado, Rea P.; Ravussin, Yann; Hulver, Matthew W.; Kozak, Leslie P.

doi:10.1074/jbc.m606114200

Cited by 229 publications

(227 citation statements)

References 51 publications

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“…During 5 weeks, 10 mice per genotype were maintained at 26°C (groups WT26 and KO26) and 10 mice per genotype were exposed to 12°C (groups WT12 and KO12) for 4 weeks, after 1 week of progressive cooling (2°C per day). The cold exposure was chosen to be moderate (12°C for 4-5 weeks) for two main reasons: (1) to avoid premature death of UCP1-KO mice since their longevity is markedly reduced when exposed to 4°C (Golozoubova et al, 2001) and (2) to avoid differences between WT and KO mice in terms of metabolic rate since it has been shown that below 12°C UCP1-KO mice might exhibit higher metabolic rates (Ukropec et al, 2006). We used an equal number of male and female mice in each experimental group (five males/five females) and the animals did not differ between groups in terms of mass [general linear model (GLM), P=0.97] and age (GLM,P=0.49) at the beginning of the experiment.…”

Section: Animal Treatmentmentioning

confidence: 99%

Mitochondrial uncoupling prevents cold-induced oxidative stress: a case study using UCP1 knock-out mice

Stier

Bize

Habold

et al. 2013

Journal of Experimental Biology

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The relationship between metabolism and reactive oxygen species (ROS) production by the mitochondria has often been (wrongly) viewed as straightforward, with increased metabolism leading to higher generation of pro-oxidants. Insights into mitochondrial functioning show that oxygen consumption is principally coupled with either energy conversion as ATP or as heat, depending on whether the ATP-synthase or the mitochondrial uncoupling protein 1 (UCP1) is driving respiration. However, these two processes might greatly differ in terms of oxidative costs. We used a cold challenge to investigate the oxidative stress consequences of an increased metabolism achieved either by the activation of an uncoupled mechanism (i.e. UCP1 activity) in the brown adipose tissue (BAT) of wild-type mice or by ATP-dependent muscular shivering thermogenesis in mice deficient for UCP1. Although both mouse strains increased their metabolism by more than twofold when acclimatised for 4 weeks to moderate cold (12°C), only mice deficient for UCP1 suffered from elevated levels of oxidative stress. When exposed to cold, mice deficient for UCP1 showed an increase of 20.2% in plasmatic reactive oxygen metabolites, 81.8% in muscular oxidized glutathione and 47.1% in muscular protein carbonyls. In contrast, there was no evidence of elevated levels of oxidative stress in the plasma, muscles or BAT of wild-type mice exposed to cold despite a drastic increase in BAT activity. Our study demonstrates differing oxidative costs linked to the functioning of two highly metabolically active organs during thermogenesis, and advises careful consideration of mitochondrial functioning when investigating the links between metabolism and oxidative stress.

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Section: Animal Treatmentmentioning

confidence: 99%

Mitochondrial uncoupling prevents cold-induced oxidative stress: a case study using UCP1 knock-out mice

Stier

Bize

Habold

et al. 2013

Journal of Experimental Biology

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“…In addition, the mechanism by which brown adipocytes (BAs) are recruited in WAT also varies: BAs in iWAT are derived from preexisting adipocytes ( 18 ), whereas BAs in gWAT originate mostly from de novo differentiation of progenitors ( 2 ). These differences in UCP1 content and source of BAs suggest that the mechanisms involved in increasing oxidative capacity in different adipose tissue depots might vary as well ( 6,19 ).…”

Section: Measurement Of Tg and Fa Concentrations And Synthesis Using mentioning

confidence: 99%

Coupling of lipolysis and de novo lipogenesis in brown, beige, and white adipose tissues during chronic β3-adrenergic receptor activation

Mottillo

Balasubramanian

Lee

et al. 2014

Journal of Lipid Research

231

204

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This article is available online at http://www.jlr.org Classic interscapular brown adipose tissue (BAT) is a thermogenic organ that has a high capacity for uncoupled oxidative metabolism ( 1 ). In contrast, white adipose tissue (WAT) has low oxidative capacity because its main function under normal conditions is to store excess energy as TGs. However, chronic stimulation by ␤ 3-adrenergic receptors ( ␤ 3-ARs) expands the oxidative capacity of WAT and converts it into a tissue resembling BAT. This phenomenon has been termed "browning" of white fat ( 2-4 ) and is marked by increased expression of oxidative genes, induction of uncoupling protein 1 (UCP1), and activation of oxidative metabolism ( 5 ). Importantly, lipolysis plays a central role in the catabolic activity of BAT and WAT. Acutely, mobilized FAs uncouple oxidative phosphorylation and provide fuel that supports both coupled and uncoupled respiration ( 6 ). Lipolysis also provides ligands for PPAR ␣ , which plays a central role in catabolic remodeling of WAT by upregulating oxidative metabolism and limiting FA-induced infl ammation ( 7,8 ). Indeed, several recent studies have demonstrated the importance of lipolysis in providing ligands for activation of PPAR target genes in BAT ( 9, 10 ), heart ( 11 ), liver ( 12, 13 ), and pancreatic ␤ cells ( 14 ).Abstract Chronic activation of ␤ 3-adrenergic receptors ( ␤ 3-ARs) expands the catabolic activity of both brown and white adipose tissue by engaging uncoupling protein 1 (UCP1)-dependent and UCP1-independent processes. The present work examined de novo lipogenesis (DNL) and TG/glycerol dynamics in classic brown, subcutaneous "beige," and classic white adipose tissues during sustained ␤ 3-AR activation by CL 316,243 (CL) and also addressed the contribution of TG hydrolysis to these dynamics. CL treatment for 7 days dramatically increased DNL and TG turnover similarly in all adipose depots, despite great differences in UCP1 abundance. Increased lipid turnover was accompanied by the simultaneous upregulation of genes involved in FAS, glycerol metabolism, and FA oxidation. Inducible, adipocyte-specifi c deletion of adipose TG lipase (ATGL), the rate-limiting enzyme for lipolysis, demonstrates that TG hydrolysis is required for CL-induced increases in DNL, TG turnover, and mitochondrial electron transport in all depots. Interestingly, the effect of ATGL deletion on induction of specifi c genes involved in FA oxidation and synthesis varied among fat depots. Overall, these studies indicate that FAS and FA oxidation are tightly coupled in adipose tissues during chronic adrenergic activation, and this effect critically depends on the activity of adipocyte ATGL. -

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“…However, chronic exposure to cold stress disturbs homeostasis, gradually resulting in an unstable internal environment and increased risk of illnesses. In animal experiments, chronic cold stress reduced the core body temperature, 2) induced hypertension, 3,4) anxiety-like behavior, 5) and suppressed immune functions, including the activity of natural killer (NK) cells 6) and antibody production. 7) Therefore, cold stress could lead to the development of dysfunctions in some organs.…”

mentioning

confidence: 99%

Processed Aconite Root Prevents Cold-Stress-Induced Hypothermia and Immuno-Suppression in Mice

Makino

Kato

Mizukami

2009

Biological & Pharmaceutical Bulletin

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Processed aconite root (PA) is a crude drug used in traditional Chinese or Japanese medicine to generate heat in interior body and dispel cold. We evaluated the effects of PA on hypothermia and reduction in the activity of natural killer (NK) cells in mice exposed to chronic cold stress. Male mice were reared at 4°C, and powdered PA was administered for 10 d as a food additive. Core body temperature of mice significantly decreased by approximately 1°C after rearing in a cold environment, and PA administration significantly restored the reduction in core body temperature in a dose-dependent manner. After 10 d, splenic NK-cell activity of cold-stressed mice was significantly reduced, and the reduction was dose-dependently recovered by PA administration. An aconitine-type alkaloid fraction prepared from PA was ineffective when administered to cold-stressed mice, and the thermogenic effect on hypothermic mice was present in the fraction containing low-molecular-weight compounds without alkaloids. In cold-stressed mice, the weight of brown adipose tissue (BAT) and uncoupling protein (UCP)-1 level in BAT increased, whereas the weight of white adipose tissue decreased. The increase in UCP-1 level in BAT of cold-stressed mice was further augmented by PA treatment. These results indicate that PA exhibited a thermogenic effect on hypothermia induced by cold stress in mice by additional upregulation of UCP-1 level in BAT, which was already enhanced by hypothermia, and that the active ingredients present in PA are nonalkaloidal low-molecular-weight compounds.

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UCP1-independent Thermogenesis in White Adipose Tissue of Cold-acclimatedUcp1^-/-Mice

Cited by 229 publications

References 51 publications

Mitochondrial uncoupling prevents cold-induced oxidative stress: a case study using UCP1 knock-out mice

Mitochondrial uncoupling prevents cold-induced oxidative stress: a case study using UCP1 knock-out mice

Coupling of lipolysis and de novo lipogenesis in brown, beige, and white adipose tissues during chronic β3-adrenergic receptor activation

Processed Aconite Root Prevents Cold-Stress-Induced Hypothermia and Immuno-Suppression in Mice

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UCP1-independent Thermogenesis in White Adipose Tissue of Cold-acclimatedUcp1-/-Mice

Cited by 229 publications

References 51 publications

Mitochondrial uncoupling prevents cold-induced oxidative stress: a case study using UCP1 knock-out mice

Mitochondrial uncoupling prevents cold-induced oxidative stress: a case study using UCP1 knock-out mice

Coupling of lipolysis and de novo lipogenesis in brown, beige, and white adipose tissues during chronic β3-adrenergic receptor activation

Processed Aconite Root Prevents Cold-Stress-Induced Hypothermia and Immuno-Suppression in Mice

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UCP1-independent Thermogenesis in White Adipose Tissue of Cold-acclimatedUcp1^-/-Mice