Stimulation of mitochondrial oxidative capacity in white fat independent of UCP1: A key to lean phenotype

Flachs, Pavel; Rossmeisl, Martin; Kuda, Ondřej; Kopecký, Jan

doi:10.1016/j.bbalip.2013.02.003

Cited by 131 publications

(142 citation statements)

References 277 publications

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“…Recently it has been demonstrated that the respiratory capacity of white adipose tissue, and potentially also of BAT, may be enhanced by the presence of n-3 polyunsaturated fatty acids in the absence of UCP1 ( 79,80 ). This increased turnover of n-3 polyunsaturated fatty acids could not be corroborated in our study, as the saturation index of BAT lipids did not change during NST.…”

Section: Physiological Role Of Brown Fatcontrasting

confidence: 55%

Brown adipose tissue dynamics in wild-type and UCP1-knockout mice: in vivo insights with magnetic resonance

Grimpo

Völker

Heppe

et al. 2014

Journal of Lipid Research

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This article is available online at http://www.jlr.org body temperature maintenance of small eutherian mammals and newborns during periods of cold exposure. BAT thermogenesis is activated by the release of noradrenaline (NA) from sympathetic innervation. Uncoupling protein 1 (UCP1) in the inner mitochondrial membrane of the brown adipocytes uncouples the respiratory chain from ATP synthesis and thus energy is dissipated as heat ( 1-3 ). Prolonged cold exposure or a short photoperiod induces the recruitment of BAT ( 4-6 ). Brown adipocytes of coldadapted mice, contain small and multilocular lipid vacuoles, which are rich in cytoplasm and have a high content of mitochondrial protein (7)(8)(9). This provides an enhanced thermogenic capacity during cold exposure, and BAT can be considered as the major site of adaptive nonshivering thermogenesis (NST) in rodents and other small mammals ( 4, 10-12 ).The breakdown of lipids via lipoprotein lipase plays an important role during UCP1-mediated heat production ( 13 ). Free fatty acids (FFAs) directly activate UCP1 and feed the respiratory chain, i.e., FFAs are the major substrate for NST ( 14,15 ). Therefore active BAT is considered as a main consumer of lipids and FFAs and its contribution to plasma clearance of administered triglycerides has been shown previously ( 16,17 ). On the other hand a release of fatty acids during thermogenesis from BAT has been assumed, indicating a substrate supply to other tissues ( 18,19 ). Sympathetic activation by cold exposure or injections of NA not only activate BAT but also stimulate sympathetic receptors in general, leading to an increase in heart rate, blood flow, and metabolic responses in other tissues. The contribution of these UCP1-independent processes to total NST remain unclear ( 20, 21 ).Abstract We used noninvasive magnetic resonance imaging (MRI) and magnetic resonance spectroscopy to compare interscapular brown adipose tissue (iBAT) of wild-type (WT) and uncoupling protein 1 (UCP1)-knockout mice lacking UCP1-mediated nonshivering thermogenesis (NST). Mice were sequentially acclimated to an ambient temperature of 30°C, 18°C, and 5°C. We detected a remodeling of iBAT and a decrease in its lipid content in all mice during cold exposure. Ratios of energy-rich phosphates (ATP/ADP, phosphocreatine/ATP) in iBAT were maintained stable during noradrenergic stimulation of thermogenesis in coldand warm-adapted mice and no difference between the genotypes was observed. As free fatty acids (FFAs) serve as fuel for thermogenesis and activate UCP1 for uncoupling of oxidative phosphorylation, brown adipose tissue is considered to be a main acceptor and consumer of FFAs. We measured a major loss of FFAs from iBAT during noradrenergic stimulation of thermogenesis. This mobilization of FFAs was observed in iBAT of WT mice as well as in mice lacking UCP1. The high turnover and the release of FFAs from iBAT suggests an enhancement of lipid metabolism, which in itself contributes to the sympathetically activated NST and which is independent fro...

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Section: Physiological Role Of Brown Fatcontrasting

confidence: 55%

Brown adipose tissue dynamics in wild-type and UCP1-knockout mice: in vivo insights with magnetic resonance

Grimpo

Völker

Heppe

et al. 2014

Journal of Lipid Research

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“…The obesity-associated WAT inflammation imposes adverse local as well as whole-body metabolic effects (1,2,11,(17)(18)(19). This inflammatory response is accompanied by macrophage repolarization to the proinflammatory (classically activated) M1 state, which negatively affects WAT functions (20) and could be counteracted using both dietary and pharmacological interventions (21,22).…”

mentioning

confidence: 99%

“…White adipose tissue (WAT) is an extremely plastic organ with important roles in energy balance, whole-body glucose homeostasis, and the immune system (1)(2)(3)(4). The systemic effects of WAT largely reflect its role in the control of blood lipid levels, as well as in the secretion of numerous bioactive peptides (e.g., adiponectin, leptin) from WAT cells (5,6).…”

mentioning

confidence: 99%

Docosahexaenoic Acid–Derived Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) With Anti-inflammatory Properties

et al. 2016

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White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obese individuals, contributes to the development of insulin resistance and type 2 diabetes. n-3 polyunsaturated fatty acids (PUFAs) of marine origin play an important role in the resolution of inflammation and exert beneficial metabolic effects. Using experiments in mice and overweight/obese patients with type 2 diabetes, we elucidated the structures of novel members of fatty acid esters of hydroxy fatty acids—lipokines derived from docosahexaenoic acid (DHA) and linoleic acid, which were present in serum and WAT after n-3 PUFA supplementation. These compounds contained DHA esterified to 9- and 13-hydroxyoctadecadienoic acid (HLA) or 14-hydroxydocosahexaenoic acid (HDHA), termed 9-DHAHLA, 13-DHAHLA, and 14-DHAHDHA, and were synthesized by adipocytes at concentrations comparable to those of protectins and resolvins derived from DHA in WAT. 13-DHAHLA exerted anti-inflammatory and proresolving properties while reducing macrophage activation by lipopolysaccharides and enhancing the phagocytosis of zymosan particles. Our results document the existence of novel lipid mediators, which are involved in the beneficial anti-inflammatory effects attributed to n-3 PUFAs, in both mice and humans.

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“…In keeping with increased overall oxidative metabolism and associated thermogenesis, ATRA treatment in mice results in an increase in rectal temperature ( 11,12 ). Enhancement of energy expenditure in WAT is a potential antiobesity strategy that can be achieved by inducing in white adipocytes UCP1-mediated thermogenesis and/or a futile substrate cycle consisting in hydrolysis of intracellular triacylglycerols and fatty acid reesterifi cation (TAG/FA cycle) ( 1 ). We have shown previously that ATRA induces UCP1 in mouse embryo fi broblasts-derived adipocytes ( 41 ) and report here a clear induction of Ucp1 gene transcription by ATRA in 3T3-L1 adipocytes.…”

Section: Discussionmentioning

confidence: 99%

All-trans retinoic acid induces oxidative phosphorylation and mitochondria biogenesis in adipocytes

Tourniaire¹,

Mušinović²,

Gouranton³

et al. 2015

Journal of Lipid Research

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Typical white adipocytes are poor in mitochondria and have a low oxidative capacity. Because of this, the contribution of white adipose tissue (WAT) to whole body energy expenditure is considered relatively small. However, there are studies in both humans and rodents documenting a negative association between mitochondrial content in WAT and obesity, as well as examples of nutritional and pharmacological interventions in animals resulting in obesity resistance that associate with increased oxidative capacity in WAT [reviewed in ( 1 )]. Stimulation of mitochondrial biogenesis and oxidative capacity in white adipocytes, when linked to increased energy expenditure in these cells through increased energy uncoupling and/or waste (e.g., futile cycles), emerges therefore as a potential novel target in the control of obesity and its related medical complications ( 1 ).Vitamin A metabolites (i.e., retinoids) modulate the growth and differentiation of a wide range of cells and tissues. Dietary vitamin A and pro-vitamin A are stored as retinyl esters or intracellularly metabolized to retinoic acid (RA), the main active form of vitamin A ( 2 ). There are two isoforms of RA, all-trans -RA (ATRA) and 9-cis -RA, which exert their effects on cell processes through both genomic and nongenomic mechanisms ( 3 ). After the liver, adipose tissue is a major site of vitamin A storage and metabolism, as well as a main target of ATRA action ( 4, 5 ).

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Stimulation of mitochondrial oxidative capacity in white fat independent of UCP1: A key to lean phenotype

Cited by 131 publications

References 277 publications

Brown adipose tissue dynamics in wild-type and UCP1-knockout mice: in vivo insights with magnetic resonance

Brown adipose tissue dynamics in wild-type and UCP1-knockout mice: in vivo insights with magnetic resonance

Docosahexaenoic Acid–Derived Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) With Anti-inflammatory Properties

All-trans retinoic acid induces oxidative phosphorylation and mitochondria biogenesis in adipocytes

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