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Caveolin-1 (cav1) is an important structural and signaling component of plasma membrane invaginations called caveolae and is abundant in adipocytes. As previously reported, adipocyte-specific ablation of the cav1 gene (ad-cav1KO mouse) does not result in elimination of the protein, as cav1 protein traffics to adipocytes from neighboring endothelial cells. However, this mouse is a functional knockout as adipocyte caveolar structures are depleted. Compared to controls, ad-cav1KO mice on a high-fat diet (HFD) display improved whole-body glucose clearance despite complete loss of glucose-stimulated insulin secretion, blunted insulin-stimulated AKT activation in metabolic tissues and partial lipodystrophy. The cause is increased insulin-independent glucose uptake by white adipose tissue (AT) and reduced hepatic gluconeogenesis. Furthermore, high fat fed ad-cav1KO mice display significant AT inflammation, fibrosis, mitochondrial dysfunction, and dysregulated lipid metabolism. The glucose clearance phenotype of the ad-cav1KO mice is at least partially mediated by AT small extracellular vesicles (AT-sEVs). Injection of control mice with AT-sEVs from ad-cav1KO mice phenocopies ad-cav1KO characteristics. Interestingly, AT-sEVs from ad-cav1KO mice propagate the phenotype of the AT to the liver. These data indicate that adipocyte cav1 is essential for healthy adaptation of the AT to overnutrition and prevents aberrant propagation of negative phenotypes to other organs by EVs.

Lipoedema is associated with widespread adipose tissue expansion, particularly in the proximal extremities. The mechanisms that drive the development of lipoedema are unclear. In this Perspective article, we propose a new model for the pathophysiology of lipoedema. We suggest that lipoedema is an oestrogen-dependent disorder of adipose tissue, which is triggered by a dysfunction of caveolin 1 (CAV1) and subsequent uncoupling of feedback mechanisms between CAV1, the matrix metalloproteinase MMP14 and oestrogen receptors. In addition, reduced CAV1 activity also leads to the activation of ERα and impaired regulation of the lymphatic system through the transcription factor prospero homeobox 1 (PROX1). The resulting upregulation of these factors could effectively explain the main known features of lipoedema, such as adipose hypertrophy, dysfunction of blood and lymphatic vessels, the overall oestrogen dependence and the associated sexual dimorphism, and the mechanical compliance of adipose tissue.

Obesity-associated type 2 diabetes mellitus (T2DM) entails insulin resistance and loss of β-cell mass. Adipose tissue mitochondrial dysfunction is emerging as a key component in the etiology of T2DM. Identifying approaches to preserve mitochondrial function, adipose tissue integrity, and β-cell mass during obesity is a major challenge. Mitochondrial ferritin (FtMT) is a mitochondrial matrix protein that chelates iron. We sought to determine whether perturbation of adipocyte mitochondria influences energy metabolism during obesity. We used an adipocyte-specific doxycycline-inducible mouse model of FtMT overexpression (FtMT-Adip mice). During a dietary challenge, FtMT-Adip mice are leaner but exhibit glucose intolerance, low adiponectin levels, increased reactive oxygen species damage, and elevated GDF15 and FGF21 levels, indicating metabolically dysfunctional fat. Paradoxically, despite harboring highly dysfunctional fat, transgenic mice display massive β-cell hyperplasia, reflecting a beneficial mitochondria-induced fat-to-pancreas interorgan signaling axis. This identifies the unique and critical impact that adipocyte mitochondrial dysfunction has on increasing β-cell mass during obesity-related insulin resistance.

Iron is essential to many fundamental biological processes, but its cellular compartmentalization and concentration must be tightly controlled. Although iron overload can contribute to obesity-associated metabolic deterioration, the subcellular localization and accumulation of iron in adipose tissue macrophages is largely unknown. Here, we show that macrophage mitochondrial iron levels control systemic metabolism in male mice by altering adipocyte iron concentrations. Using various transgenic mouse models to manipulate the macrophage mitochondrial matrix iron content in an inducible fashion, we demonstrate that lowering macrophage mitochondrial matrix iron increases numbers of M2-like macrophages in adipose tissue, lowers iron levels in adipocytes, attenuates inflammation and protects from high-fat-diet-induced metabolic deterioration. Conversely, elevating macrophage mitochondrial matrix iron increases M1-like macrophages and iron levels in adipocytes, exacerbates inflammation and worsens high-fat-diet-induced metabolic dysfunction. These phenotypes are robustly reproduced by transplantation of a small amount of fat from transgenic to wild-type mice. Taken together, we identify macrophage mitochondrial iron levels as a crucial determinant of systemic metabolic homeostasis in mice.

Adipocytes undergo intense energetic stress in obesity resulting in loss of mitochondrial mass and function. We have found that adipocytes respond to mitochondrial stress by rapidly and robustly releasing small extracellular vesicles (sEVs). These sEVs contain respiration-competent, but oxidatively damaged mitochondrial particles, which enter circulation and are taken up by cardiomyocytes, where they trigger a burst of ROS. The result is compensatory antioxidant signaling in the heart that protects cardiomyocytes from acute oxidative stress, consistent with a preconditioning paradigm. As such, a single injection of sEVs from energetically stressed adipocytes limits cardiac ischemia/reperfusion injury in mice. This study provides the first description of functional mitochondrial transfer between tissues and the first vertebrate example of "inter-organ mitohormesis." Thus, these seemingly toxic adipocyte sEVs may provide a physiological avenue of potent cardio-protection against the inevitable lipotoxic or ischemic stresses elicited by obesity.

The adipose tissue stroma is a rich source of molecularly distinct stem and progenitor cell populations with diverse functions in metabolic regulation, adipogenesis, and inflammation. The ontology of these populations and the mechanisms that govern their behaviors in response to stimuli, such as overfeeding, however, are unclear. Here, we show that the developmental fates and functional properties of adipose platelet-derived growth factor receptor beta (PDGFRβ)+ progenitor subpopulations are tightly regulated by mitochondrial metabolism. Reducing the mitochondrial β-oxidative capacity of PDGFRβ+ cells via inducible expression of MitoNEET drives a pro-inflammatory phenotype in adipose progenitors and alters lineage commitment. Furthermore, disrupting mitochondrial function in PDGFRβ+ cells rapidly induces alterations in immune cell composition in lean mice and impacts expansion of adipose tissue in diet-induced obesity. The adverse effects on adipose tissue remodeling can be reversed by restoring mitochondrial activity in progenitors, suggesting therapeutic potential for targeting energy metabolism in these cells.

Dermal adipose tissue (also known as dermal white adipose tissue and herein referred to as dWAT) has been the focus of much discussion in recent years. However, dWAT remains poorly characterized. The fate of the mature dermal adipocytes and the origin of the rapidly reappearing dermal adipocytes at different stages remain unclear. Here, we isolated dermal adipocytes and characterized dermal fat at the cellular and molecular level. Together with dWAT's dynamic responses to external stimuli, we established that dermal adipocytes are a distinct class of white adipocytes with high plasticity. By combining pulse-chase lineage tracing and single-cell RNA sequencing, we observed that mature dermal adipocytes undergo dedifferentiation and redifferentiation under physiological and pathophysiological conditions. Upon various challenges, the dedifferentiated cells proliferate and redifferentiate into adipocytes. In addition, manipulation of dWAT highlighted an important role for mature dermal adipocytes for hair cycling and wound healing. Altogether, these observations unravel a surprising plasticity of dermal adipocytes and provide an explanation for the dynamic changes in dWAT mass that occur under physiological and pathophysiological conditions, and highlight the important contributions of dWAT toward maintaining skin homeostasis.

The synthesis of lipid and sterol species through de novo lipogenesis (DNL) is regulated by two functionally overlapping but distinct transcription factors: the sterol regulatory element-binding proteins (SREBPs) and carbohydrate response element binding protein (ChREBP). ChREBP is considered to be the dominant regulator of DNL in adipose tissue (AT); however, the SREBPs are highly expressed and robustly regulated in adipocytes, suggesting that the model of AT DNL may be incomplete. Here we describe a new mouse model of inducible, adipocyte-specific overexpression of the insulin-induced gene 1 (Insig1), a negative regulator of SREBP transcriptional activity. Contrary to convention, Insig1 overexpression did block AT lipogenic gene expression. However, this was immediately met with a compensatory mechanism triggered by redox activation of mTORC1 to restore SREBP1 DNL gene expression. Thus, we demonstrate that SREBP1 activity sustains adipocyte lipogenesis, a conclusion that has been elusive due to the constitutive nature of current mouse models.

Excess calories stored in white adipose tissue (WAT) could be reduced either through the activation of brown adipose tissue (BAT) or the development of brown-like cells (“beige” or “brite”) in WAT, a process named “browning.” Calorie dissipation in brown and beige adipocytes might rely on the induction of uncoupling protein 1 (UCP1), which is absent in white fat cells. Any increase in UCP1 is commonly considered as the trademark of energy expenditure. The intracellular events involved in the recruitment process of beige precursors were extensively studied lately, as were the effectors, hormones, cytokines, nutrients and drugs able to modulate the route of browning and theoretically affect fat mass in rodents and in humans. The aim of this review is to update the characterization of the extracellular effectors that induce UCP1 in WAT and potentially provoke calorie dissipation. The potential influence of metabolic cycling in energy expenditure is also questioned.

1873-6750 Joffin, Nolwenn Noirez, Philippe Antignac, Jean-Philippe Kim, Min-Ji Marchand, Philippe Falabregue, Marion Le Bizec, Bruno Forest, Claude Emond, Claude Barouki, Robert Coumoul, Xavier Journal Article Netherlands Environ Int. 2018 Oct 31. pii: S0160-4120(18)31382-5. doi: 10.1016/j.envint.2018.10.027.; International audience; BackgroundPersistent organic pollutants (POPs) are known to accumulate in adipose tissues (AT). This storage may be beneficial by diverting POPs from other sensitive tissues or detrimental because of chronic release of pollutants as indirectly suggested during weight loss. The aim is to study the biological and/or toxic effects that chronic POP release from previously contaminated grafted AT could exert in a naïve mouse.MethodsC57BL/6J male mice were exposed intraperitoneally to 2,3,7,8-tetrachlorodibenzo-p-doxin (TCDD); their epididymal fat pads were collected and grafted on the back skin of uncontaminated recipient mice whose brain, liver, and epididymal ATs were analyzed (TCDD concentration, relevant gene expression). Kinetics of release and redistribution were modeled using Physiologically Based PharmacoKinetics (PBPK).ResultsThe grafts released TCDD over a period of 10 weeks with different kinetics of distribution in the three organs studied. A PBPK model was used to simulate the AT releasing process and the incorporation of TCDD into the major organs. At three weeks post-graft, we observed significant changes in gene expression in the liver and the host AT with signatures reminiscent of inflammation, gluconeogenesis and fibrosis as compared to the control.ConclusionsThis study confirms that AT-stored TCDD can be released and distributed to the organs of the recipient hence leading to distinct changes in gene expression. This original model provides direct evidence of the potential toxic-relevant effects when endogenous sources of contamination are present.

We recently demonstrated that citrulline (CIT) reduced the expression of inflammatory genes in cultured explants from retroperitoneal (RET) white adipose tissue (WAT) from young (2–4 months) but not old (25 months) rats. Here we show that in RET WAT from old rats and high-fat-diet-fed (HFD) young rats, the basal expression of the leptin gene was increased (275–345%) whereas that of the adiponectin gene was decreased (48–60%), when compared to those from control-diet-fed (CD) young rats. We show also that in RET WAT from old rats, a diet supplemented with CIT for 3 months reduced macrophage (F4/80, CD68) and inflammation (interleukin-6, tumor necrosis factor-α) marker genes 23–97%. CIT supplementation lowered leptin mRNA 62% and increased adiponectin mRNA 232%. In cultured explants of RET WAT from 4 month-old CD, 4 month-old HFD and 25-month-old CD rats, the exposure to 2.5 mmol/L CIT for 24 h up-regulated adiponectin gene expression 151%, 362% and 216% respectively. In contrast, leptin gene expression was down-regulated 66% selectively in CIT-treated explants from 25-month-old CD rats. These results further support the proposed beneficial effect of CIT to counteract the deleterious effects of aging and overweight on the metabolic, inflammatory and endocrine functions of WAT., Highlights • HFD and aging increase leptin mRNA and decrease adiponectin mRNA in rat adipose tissue. • In old rats a CIT diet reduces leptin mRNA and augments adiponectin mRNA. • In adipose tissue explants, CIT induces adiponectin mRNA whatever age and diet. • CIT exposure of adipose tissue explants reduces leptin mRNA selectively in old rats.

Low oxygen levels are a hallmark of expanding fat tissue in obesity, and can lead to type 2 diabetes. In addition to a lack of adequate blood supply, increased oxygen demand in fat cells now emerges as being key to this harmful state. Intracellular oxygen demand increases hypoxia in expanding fat tissue.

Despite many angiogenic factors playing crucial roles in metabolic homeostasis, effects of angiopoietin-2 (ANG-2) in adipose tissue (AT) remain unclear. Utilizing a doxycycline-inducible AT-specific ANG-2 overexpression mouse model, we assessed the effects of ANG-2 in AT expansion upon a high-fat diet (HFD) challenge. ANG-2 is significantly induced, with subcutaneous white AT (sWAT) displaying the highest ANG-2 expression. ANG-2 overexpressing mice show increased sWAT vascularization and are resistant to HFD-induced obesity. In addition, improved glucose and lipid metabolism are observed. Mechanistically, the sWAT displays a healthier expansion pattern with increased anti-inflammatory macrophage infiltration. Conversely, ANG-2 neutralization in HFD-challenged wild-type mice shows reduced vascularization in sWAT, associated with impaired glucose tolerance and lipid clearance. Blocking ANG-2 causes significant pro-inflammatory and pro-fibrotic changes, hallmarks of an unhealthy AT expansion. In contrast to other pro-angiogenic factors, such as vascular endothelial growth factor-A (VEGF-A), this is achieved without any enhanced beiging of white AT. DOI: http://dx.doi.org/10.7554/eLife.24071.001

We have uncovered the existence of extracellular vesicle (EV)-mediated signaling between cell types within the adipose tissue (AT) proper. This phenomenon became evident in our attempts at generating an adipocyte-specific knockout of caveolin 1 (cav1) protein. Although we effectively ablated the CAV1 gene in adipocytes, cav1 protein remained abundant. With the use of newly generated mouse models, we show that neighboring endothelial cells (ECs) transfer cav1-containing EVs to adipocytes in vivo, which reciprocate by releasing EVs to ECs. AT-derived EVs contain proteins and lipids capable of modulating cellular signaling pathways. Furthermore, this mechanism facilitates transfer of plasma constituents from ECs to the adipocyte. The transfer event is physiologically regulated by fasting/refeeding and obesity, suggesting EVs participate in the tissue response to changes in the systemic nutrient state. This work offers new insights into the complex signaling mechanisms that exist among adipocytes, stromal vascular cells, and, potentially, distal organs.

Introduction et but de l’etude Une exposition a la citrulline (CIT) pendant 24 h d’explants de tissu adipeux blanc intra-abdominal (WAT) issus de rats en surpoids par un regime hyperlipidique (HFD) provoque la liberation des acides gras et stimule la beta oxydation [1] . Des mecanismes de « brunisation » du WAT, augmentant la thermogenese sans frisson et la depense energetique ont ete decrits. Celle-ci implique l’induction de la proteine decouplante (UCP1), longtemps consideree comme specifique du tissu adipeux brun. Nous avons etudie l’effet potentiel de la CIT sur l’induction de l’UCP1 dans des explants de WAT retroperitoneal (RET) et peri-epididymaire (EPI). Materiel et methodes Les explants de WAT issus de rats Sprague-Dawley de quatre mois, ayant ete maintenus pendant deux mois soit sous regime standard (CD, n = 7), soit HFD ( n = 7), ont ete exposes a 2,5 mmoles/L de citrulline pendant 8 h ou 24 h. Les ARN totaux et les proteines ont ete prepares. L’expression d’UCP1 et celle de son ARNm ont ete etudiees par western blot et par RT-qPCR. Les niveaux d’expression des ARNm des deux principaux regulateurs de l’expression du gene UCP1 , le recepteur active par les proliferateurs de peroxysomes alpha (PPARα) et le PPARγ-coactivateur-1-α (PGC-1α), ont aussi ete analyses par RT-qPCR. Resultats et analyse statistique Dans les explants des tissus RET et EPI de rats HFD, l’expression de l’ARNm UCP1 et celle de sa proteine sont diminuees respectivement de 45–55 % et de 40–50 % ( p [2] . A la suite de l’exposition des explants des deux tissus a la CIT pendant 24 h, l’expression de l’ARNm UCP1 et celle de la proteine UCP1 sont augmentees respectivement de 3,5–6 fois ( p p [2] . L’expression des ARNm PPARα et PGC-1α est aussi induite par la CIT dans les explants des deux tissus respectivement de 3,2–6 fois et 2,2–5,5 fois ( p Conclusion La CIT induit tres rapidement l’expression d’UCP1 et de deux des principaux regulateurs de l’expression de son gene, dans des explants de WAT. La stimulation de l’expression d’UCP1 sous l’effet de CIT, conduirait a la « brunisation » du WAT comme mediatrice de depense energetique permettant de lutter contre le surpoids induit par un regime riche en lipides. Ces resultats identifient un nouveau mecanisme d’action benefique de la CIT sur la sante.

International audience; A diet enriched with citrulline (CIT) reduces white adipose tissue (WAT) mass. We recently showed that CITstimulated β-oxidation in rat WAT explants from young (2–4 months) but not old (25 months) rats. Here we show thatboth in old rats and high-fat-diet-fed young rats, uncoupling protein one (UCP1) mRNA and protein expressions wereweaker than those in young control rats. Selectively in WAT from young rats, a 24h CIT treatment up-regulatedexpressions of UCP1, peroxisome proliferator-activated receptor-x (PPARx/, PPARy-coactivator-1-x and mitochondrialtranscription-factor-A whereas it down-regulated PPARy gene expression, whatever the diet. These results suggestthat CIT induces a new metabolic status in WAT, with increased β-oxidation and uncoupling of respiratory chain,resulting in energy expenditure that favors fat mass reduction.

International audience; SCOPE:High-fat diet (HFD) increases visceral adipose tissue (AT). Our aim was to evaluate whether citrulline (CIT) affected nonesterified fatty acid (NEFA) metabolism in AT from HFD-fed rats.METHODS AND RESULTS:Rats were fed for 8 weeks with either a control diet (CD) or HFD. Retroperitoneal AT explants were exposed to 2.5 mmol/L CIT for 24 h. We analyzed lipolysis, beta-oxidation, glyceroneogenesis, and the expression of the key associated enzymes. CIT doubled NEFA release selectively in HFD AT. Phosphorylation of hormone-sensitive lipase was upregulated 50 and 100% by CIT in CD and HFD AT, respectively. Under CIT, beta-oxidation increased similarly whatever the diet, whereas glyceroneogenesis, which permits NEFA re-esterification, was downregulated 50 and 80% in CD and HFD AT, respectively. In the latter, the important decrease in re-esterification probably explains the rise of NEFA release. A pretreatment with the nitric oxide synthase inhibitor N ω-nitro-l-arginine methyl ester abolished CIT effects.CONCLUSION:These results demonstrate direct lipolytic and antiglyceroneogenic effects of CIT on CD and HFD AT. The selective CIT-mediated NEFA release from HFD AT was probably the consequence of the drastic decrease in glyceroneogenesis and nitric oxide was a mediator of CIT effects. These results provide evidence for a direct action of CIT on AT to reduce overweight.

Since the initial identification of leptin as the product of the ob gene in 1994, the signaling pathways by which this hormone alters cell physiology have been the subject of extensive investigations. The fact that leptin can induce nitric oxide (NO) production was first demonstrated in studies of the pituitary gland and pancreatic islets. A large number of additional studies further showed that this adipokine stimulates NO synthesis in multiple tissues. This review article discusses the role of leptin in NO production and its pathophysiological consequences. The role of this gaseous messenger in cell physiology depends on the cell type, the concentration of NO and the duration of exposure. It can be either a potent oxidant or a protector of cell integrity against the formation of reactive oxygen species. Leptin plays two opposing roles on arterial pressure. It exerts a hypertensive effect due to sympathetic activation and a vasorelaxant effect due to NO production. This adipokine acts via NO to produce pro-inflammatory factors in cartilage pathology, potentially contributing to an increased risk for osteoarthritis. Another well-documented role of leptin-induced NO, acting either directly or via the hypothalamus, concerns lipid metabolism in muscle and adipose tissue. In adipocytes, the direct and rapid action of leptin is to activate the nitric oxide synthase III, which favors lipolysis. In contrast, in the long-term, leptin reduces lipolysis. However, both in the short-term and in the long-term, glyceroneogenesis and its key enzyme, the cytosolic phosphoenolpyruvatecarboxykinase (PEPCK-C), are down-regulated by the adipokine, thus favoring fatty acid release. Hence, leptin-induced NO production plays a crucial role in fatty acid metabolism in adipose tissue. The resulting effects are to prevent lipid storage and to improve energy expenditure, with possible improvements of the obese state and its associated diseases.

L’obesite s’accompagne de pathologies comme le diabete de type 2 et les maladies cardiovasculaires, liees a des deregulations metaboliques et endocriniennes du tissu adipeux blanc (TAB). Au cours du vieillissement, la perte de masse musculaire peut etre associee a l’obesite et definit le concept d’obesite sarcopenique. Les traitements mis en œuvre pour contrecarrer ces pathologies n’ont qu’un succes tres partiel. Il est donc opportun de developper des strategies alternatives originales qui pourraient aboutir a des therapeutiques ciblees. Notre equipe etudie les regulations metaboliques du TAB, source majeure de stockage de l’energie de l’organisme. Les triglycerides stockes sont liberes a jeun grâce a la lipolyse qui libere les acides gras non-esterifies (AGNE) et le glycerol dans le sang, comme source d’energie des autres tissus. En plus de la β-oxydation des AGNE, leur re-esterification partielle intervient pour limiter leur liberation lors de la lipolyse. La glyceroneogenese est necessaire a la re-esterification en situation de jeune. Des etudes prealables ont montre que l'administration de citrulline (CIT) pendant trois mois a des rats vieillissants induit une diminution d’environ 40% de la masse viscerale du TAB. Cet acide amine non proteique est un complement alimentaire donne au cours du vieillissement ou a des sportifs pour augmenter la masse musculaire. Nous avons etudie les effets de la CIT sur des cultures d’explants de TAB de rats. Dans la premiere partie de ce travail, nous montrons que la CIT a un effet direct lipolytique et anti-glyceroneogenique sur les explants des rats qu’ils soient jeunes ou âges. Cependant, la liberation des AGNE du TAB des rats jeunes est limitee par une augmentation de la capacite oxydative du tissu. Avec l’âge, la masse du TAB augmente en parallele a l’augmentation d’un etat pro-inflammatoire. Afin de comprendre l’influence de ces deux parametres independamment de l’âge, nous avons etudie dans la deuxieme partie de ce travail, les effets de la CIT sur les explants de TAB de rats jeunes soumis a un regime controle (CD) ou hyperlipidique (HFD). Nous observons une augmentation, induite par la CIT, de la lipolyse et de la capacite s-oxydative du TAB des rats quel que soit le regime, alors que la glyceroneogenese est diminuee. Toutefois, les AGNE sont selectivement liberes par le TAB de rats HFD, en relation avec une reduction drastique de leur re-esterification. Le NO est un mediateur de ces effets. Dans une troisieme partie, nous demontrons que la CIT agit directement sur le TAB de rats CD et HFD pour induire l'expression de la proteine decouplante, UCP1, en lien avec le « brunissement » potentiel du TAB par cet acide amine. Ces effets ne sont pas observes au sein du TAB des rats âges. L’ensemble de nos resultats etablit les bases pour de futures investigations visant a elucider les mecanismes par lesquels la CIT reduit la masse adipeuse et ouvre de nouvelles perspectives therapeutiques pour lutter contre le surpoids et l’obesite sarcopenique.

Introduction et but de l’etude La complementation en citrulline (CIT) chez le rat âge reduit la masse adipeuse viscerale. Nous avons montre que la CIT exerce une action lipolytique et anti-gly-ceroneogenique directe sur le tissu adipeux (TA) quel que soit l’âge. Uniquement chez le rat jeune, l’induction de la liberation des acides gras (AG) est compensee par une augmentation de s-oxydation [1]. Le vieillissement etant lie a une augmentation du TA, nous avons fait l’hypothese que la CIT exerce aussi une action lipolytique dans le TA de rat jeunes en surpoids. Materiel et methodes Nous avons traite par la CIT (2,5mM, 24 h) des explants de TA retroperitoneal issus de rats de 4 mois, maintenus pendant 2 mois soit sous regime standard (CD ; n =7) soit riche en lipides (HFD ; n =7) pour induire un surpoids. L’index de lipolyse a ete evalue par la concentration d’AG et de glycerol dans le milieu. La glyceroneogenese, marqueur de la re-esterification des AG, a ete estimee par incorporation du 14 C du [1- 14 C]-pyruvate dans les lipides. La capacite oxydative a ete quantifiee par l’ 3 H 2 O produite a partir du (9,10 −3 H)-palmitate. L’expression des enzymes impliquees a ete etudiee par RT-qPCR et western blot. Les analyses statistiques ont ete realisees par le test de Mann-Whitney. Resultats et Analyse statistique La liberation des AG est stimulee par la CIT selectivement dans le TA de rats HFD (100 %, **P Conclusion La CIT modifie profondement le metabolisme des AG dans le TA. Chez les rats jeunes, quel que soit le regime, elle augmente la lipolyse et la capacite oxydative et diminue la glyceroneogenese, donc la re-esterification des AG. La s-oxydation augmentee chez les rats CD permet d’expliquer que les AG ne sont pas liberes car utilises comme source energetique. La diminution drastique de la re-esterification chez les rats HFD n’est pas completement compensee par l’induction de beta-oxydation, ce qui entraine la liberation d’une partie des AG [2] qui peuvent alors etre utilises comme substrat energetique par d’autres tissus tels que le muscle. Ces resultats suggerent que la CIT « vide » les adipocytes des triglycerides de stockage et pourraient rendre compte d’une diminution de masse du TA visceral induite par un regime enrichi en CIT.