京都大学 / 0048 / 新制・課程博士 / 博士(薬学) / 甲第18212号 / 薬博第802号 / 新制||薬||237(附属図書館) / 31070 / 京都大学大学院薬学研究科生命薬科学専攻 / (主査)教授 中山 和久, 教授 竹島 浩, 教授 根岸 学 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

No description available.

No description available.

No description available.

Lam Tsz Yan. / Thesis submitted in: October 2007. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references. / Abstracts in English and Chinese. / Abstract (English) --- p.i / 論文摘要 --- p.iv / Acknowledgements --- p.vi / Publications --- p.vii / Abbreviations --- p.ix / Contents --- p.x / Chapter 1. --- General Introduction --- p.1 / Chapter 1.1. --- Obesity --- p.1 / Chapter 1.1.1. --- Overview --- p.1 / Chapter 1.1.2. --- Pathophysiology --- p.1 / Chapter 1.1.3. --- Central obesity --- p.3 / Chapter 1.2. --- Diabetes --- p.7 / Chapter 1.2.1. --- Overview --- p.7 / Chapter 1.2.2. --- Pathophysiology --- p.8 / Chapter 1.3. --- Lipolysis --- p.9 / Chapter 1.3.1. --- Proteins participating in triglyceride lipolysis --- p.10 / Chapter 1.3.1.1. --- Hormone-sensitive lipase (HSL) --- p.10 / Chapter 1.3.1.2. --- Adipose triglyceride lipase (ATGL) --- p.10 / Chapter 1.3.1.3. --- Perilipins --- p.11 / Chapter 1.3.2. --- Abnormal regulation of lipolysis in obesity --- p.11 / Chapter 1.3.3. --- Disturbed lipolysis in insulin resistance --- p.13 / Chapter 1.4. --- Pharmacotherapy --- p.13 / Chapter 1.4.1. --- Obesity --- p.13 / Chapter 1.4.1.1. --- Orlistat --- p.13 / Chapter 1.4.1.2. --- Sibutramine --- p.14 / Chapter 1.4.1.3. --- Others --- p.15 / Chapter 1.4.2. --- Diabetes --- p.15 / Chapter 1.4.2.1. --- Modulation of the β-cells functions --- p.15 / Chapter 1.4.2.2. --- Control of glucose output --- p.16 / Chapter 1.4.2.3. --- Modulation of carbohydrate absorption --- p.16 / Chapter 1.4.2.4. --- Thiazolidinediones (TZDs) --- p.16 / Chapter 1.5. --- Animal models used in type 2 diabetes and obesity research --- p.17 / Chapter 1.6. --- Aim of study --- p.18 / Chapter 2. --- β-Adrenoceptors (β-ARs) --- p.21 / Chapter 2.1. --- Introduction --- p.21 / Chapter 2.1.1. --- Hormonal control of lipolysis --- p.21 / Chapter 2.1.1.1. --- Catecholamines --- p.21 / Chapter 2.1.1.2. --- Insulin --- p.23 / Chapter 2.1.2. --- Folic acid (folate) --- p.23 / Chapter 2.1.2.1. --- Physiological roles of folate --- p.23 / Chapter 2.1.2.2. --- Folate deficiency and its consequences --- p.24 / Chapter 2.1.2.3. --- Hyperhomocysteinemia --- p.24 / Chapter 2.1.2.4. --- Pleiotropic effects of folate --- p.25 / Chapter 2.1.2.5. --- Role of folate in type 2 diabetes and obesity --- p.26 / Chapter 2.1.3. --- Lingzhi --- p.28 / Chapter 2.1.3.1. --- Triterpenoids --- p.29 / Chapter 2.1.3.2. --- Polysaccharides --- p.30 / Chapter 2.2. --- Materials and methods --- p.32 / Chapter 2.2.1. --- Materials --- p.32 / Chapter 2.2.1.1. --- Composition of physiological salt solution --- p.32 / Chapter 2.2.1.2. --- Materials used in lipolysis experiment --- p.32 / Chapter 2.2.1.3. --- Materials used in reverse transcription polymerase chain reaction (RT-PCR) --- p.34 / Chapter 2.2.1.4. --- Materials used in Western blotting --- p.34 / Chapter 2.2.2. --- Methods --- p.36 / Chapter 2.2.2.1. --- Lipolysis experiment --- p.36 / Chapter 2.2.2.1.1. --- Animals --- p.36 / Chapter 2.2.2.1.2. --- Drug administration --- p.36 / Chapter 2.2.2.1.3. --- Isolation of adipocytes --- p.37 / Chapter 2.2.2.1.4. --- Lipolysis measurement --- p.37 / Chapter 2.2.2.1.5. --- Data analysis --- p.38 / Chapter 2.2.2.2. --- RT-PCR --- p.38 / Chapter 2.2.2.2.1. --- Tissue preparation --- p.39 / Chapter 2.2.2.2.2. --- RNA extraction --- p.39 / Chapter 2.2.2.2.3. --- Reverse transcription (RT) --- p.40 / Chapter 2.2.2.2.4. --- Polymerase chain reaction (PCR) --- p.40 / Chapter 2.2.2.2.5. --- Agarose gel electrophoresis --- p.41 / Chapter 2.2.2.2.6. --- Data representation and analysis --- p.41 / Chapter 2.2.2.3. --- Western blotting --- p.42 / Chapter 2.2.2.3.1. --- Tissue preparation --- p.42 / Chapter 2.2.2.3.2. --- Protein extraction --- p.42 / Chapter 2.2.2.3.3. --- Western blotting --- p.42 / Chapter 2.2.2.3.4. --- Data representation and analysis --- p.43 / Chapter 2.3. --- Results --- p.43 / Chapter 2.3.1. --- Studies on the β-adrenoceptor-mediated lipolytic response in +m/+db and +db/+db mice --- p.43 / Chapter 2.3.1.1. --- Effect of β2-adrenoceptor agonist on lipolysis --- p.43 / Chapter 2.3.1.2. --- Effect of β3-adrenoceptor agonists and their antagonists on lipolysis --- p.44 / Chapter 2.3.1.3. --- Effect of non-selective β-adrenoceptor agonists and their antagonists on lipolysis --- p.45 / Chapter 2.3.1.4. --- Effect of modulators of intracellular cyclic nucleotide monophosphate on lipolysis --- p.46 / Chapter 2.3.1.5. --- Effect of exogenously delivered nitric oxide on lipolysis --- p.47 / Chapter 2.3.1.6. --- Gene expression of β-adrenoceptors in white adipose tissue --- p.47 / Chapter 2.3.1.7. --- Protein expression of β-adrenoceptors in white adipose tissue --- p.47 / Chapter 2.3.2. --- Effect of folic acid treatment on lipolysis --- p.48 / Chapter 2.3.2.1. --- Determination of body weight --- p.48 / Chapter 2.3.2.2. --- Effect of β2-adrenoceptor agonist on lipolysis --- p.48 / Chapter 2.3.2.3. --- Effect of β-adrenoceptor agonists on lipolysis --- p.49 / Chapter 2.3.2.4. --- Effect of non-selective β-adrenoceptor agonist on lipolysis --- p.50 / Chapter 2.3.2.5. --- Effect of modulators of intracellular cyclic nucleotide monophosphate on lipolysis --- p.51 / Chapter 2.3.2.6. --- Effect of exogenously delivered nitric oxide on lipolysis --- p.52 / Chapter 2.3.2.7. --- Gene expression of β-adrenoceptors in white adipose tissue --- p.52 / Chapter 2.3.2.8. --- Protein expression of β-adrenoceptors in white adipose tissue --- p.53 / Chapter 2.3.3. --- Effect of Lingzhi (water-extract) treatment on lipolysis --- p.54 / Chapter 2.3.3.1. --- Determination of body weight --- p.54 / Chapter 2.3.3.2. --- Lipolytic effect of forskolin --- p.54 / Chapter 3. --- Peroxisome Proliferator-Activated Receptor-y (PPAR-γ) --- p.91 / Chapter 3.1. --- Introduction --- p.91 / Chapter 3.1.1. --- Peroxisome proliferator-activated receptors --- p.91 / Chapter 3.1.1.1. --- Peroxisome proliferator-activated receptor-γ --- p.91 / Chapter 3.1.1.1.1. --- "PPAR-γ in obesity, lipid metabolism and type 2 diabetes" --- p.91 / Chapter 3.1.1.1.2. --- PPAR-γ in inflammation and atherosclerosis --- p.92 / Chapter 3.1.1.2. --- PPAR-γ and thiazolidinediones --- p.93 / Chapter 3.2. --- Materials and method --- p.95 / Chapter 3.2.1. --- Materials --- p.95 / Chapter 3.2.1.1. --- Composition of physiological salt solution --- p.95 / Chapter 3.2.1.2. --- Materials used in lipolysis experiment --- p.95 / Chapter 3.2.1.3. --- Materials used in RT-PCR --- p.95 / Chapter 3.2.1.4. --- Materials used in Western blotting --- p.95 / Chapter 3.2.2. --- Methods --- p.96 / Chapter 3.2.2.1. --- Lipolysis experiment --- p.96 / Chapter 3.2.2.2. --- RT-PCR --- p.96 / Chapter 3.2.2.3. --- Western blotting --- p.97 / Chapter 3.3. --- Results --- p.97 / Chapter 3.3.1. --- Effect of PPAR-γ agonists on lipolysis --- p.97 / Chapter 3.3.2. --- Gene expression of PPAR-γ in white adipose tissue --- p.97 / Chapter 3.3.3. --- Protein expression of PPAR-γ in white adipose tissue --- p.97 / Chapter 4. --- 3-Hydoxy-3-MethylgIutaryl Coenzyme A (HMG-CoA) Reductase --- p.106 / Chapter 4.1. --- Introduction --- p.106 / Chapter 4.1.1. --- Cholesterol metabolism and cardiovascular diseases --- p.106 / Chapter 4.1.2. --- Statins --- p.106 / Chapter 4.1.2.1. --- Modes of action --- p.107 / Chapter 4.1.2.2. --- Therapeutic efficacy of statins --- p.108 / Chapter 4.1.2.2.1. --- Diabetes --- p.108 / Chapter 4.1.2.2.2. --- Coronary artery disease --- p.109 / Chapter 4.1.3. --- Distribution and expression of HMG-CoA reductase --- p.109 / Chapter 4.2. --- Materials and method --- p.110 / Chapter 4.2.1. --- Materials --- p.110 / Chapter 4.2.1.1. --- Composition of physiological salt solution --- p.110 / Chapter 4.2.1.2. --- Materials used in lipolysis experiment --- p.110 / Chapter 4.2.1.3. --- Materials used in RT-PCR --- p.110 / Chapter 4.2.1.4. --- Materials used in Western blotting --- p.110 / Chapter 4.2.2. --- Methods --- p.110 / Chapter 4.2.2.1. --- Lipolysis experiment --- p.110 / Chapter 4.2.2.2. --- RT-PCR --- p.111 / Chapter 4.2.2.3. --- Western blotting --- p.111 / Chapter 4.3. --- Results --- p.112 / Chapter 4.3.1. --- Effect of statins on lipolysis --- p.112 / Chapter 4.3.2. --- Gene expression of HMG-CoA reductase in various internal organs --- p.112 / Chapter 4.3.3. --- Protein expression of HMG-CoA reductase in various internal organs --- p.113 / Chapter 5. --- Discussion --- p.122 / Chapter 5.1. --- β-adrenoceptor-mediated lipolysis --- p.122 / Chapter 5.2. --- Studies on peroxisome proliferator-activated receptor-γ --- p.140 / Chapter 5.3. --- Studies on HMG-CoA reductase --- p.142 / Chapter 5.4. --- Further studies --- p.147 / Chapter 5.5. --- Conclusions --- p.148 / Chapter 6. --- References --- p.152

Lipid-based drug delivery systems (LBDDSs) are becoming an increasingly popular approach to improve the oral absorption of poorly-water soluble drugs. Several possible mechanisms have been proposed to explain the means by which LBDDSs act in vivo to enhance absorption. The goal of the current dissertation is to provide a better understanding of one proposed mechanism; the capability of lipoidal components in LBDDS formulations to create and maintain a drug in a supersaturated state under simulated GI conditions. Moreover, molecular details of equilibrium solubilization of a drug in a series of model lipid assemblies were examined. The results of these studies will aid formulators in choosing the optimal LBDDS to improve oral absorption of poorly water-soluble drugs. Time-dependent solubilization behavior of progesterone, 17β-estradiol and nifedipine in a simple model LBDDS composed of Polysorbate 80 was assessed employing the in vitro dynamic lipolysis model. The results illustrated the extent to which the supersaturated state was dependent on the extent of lipolysis of Polysorbate 80 and the initial drug concentration. Area-under-the curve-supersaturation was proposed as a means of quantifying the time-dependent extent of supersaturation in LBDDSs in simulated intestinal conditions. Concurrently, a series of model mixed micellar solutions, composed of Polysorbate 80 and oleic acid, were prepared to represent the lipid assemblies produced during the lipolysis experiments. The ability of these aggregates to solubilize progesterone, 17β-estradiol and nifedipine were evaluated and the aggregate/water partition coefficients were determined. The Treinor model was found to successfully fit the partition coefficients of the drugs in a range of mixed micelles. The equilibrium solubility of drugs in the mixed micelles was calculated and compared to that found under lipolytic conditions. The best agreement between calculated and experimental conditions was observed for nifedipine. These studies have established a foundation for the evaluation of time-dependent extent of supersaturation with more complex LBDDS formulations exposed to lipolytic conditions.

pccenturion@gmail.com / Introduction: Liposuction has undergone several improvements since its first description, including changes in the cannulas, variation in the concentration of the infiltrating solution, and the use of different devices and technologies. The use of laser technology devices for lipolysis and stimulation of skin retraction has contributed to the procedure. This article presents the authors’ experience with laser lipolysis in 400 patients, within a 5-year period, and discusses the principles of the technology and its effect on tissues. Methods: This is a study performed between July 2007 and July 2012 and included 400 patients who underwent laser lipolysis. All procedures were performed following the original protocol – infiltration of cold saline, passage of the cannula with an optic fiber for conducting the energy needed for laser lipolysis, skin retraction, and finally, conventional liposuction. Results: Hospitalization type ranged from outpatient to overnight surgery. Approximately 45% (180 of 400) of patients had minimal bruising, with involvement of 2% or more of the affected body surface. Hematoma, seroma, and dehiscence occurred in a total of 9% (36 of 400) of patients. We did not find any case of thermal burn of the skin. Conclusions: Laser lipolysis performed according to the described technique was safe and reproducible. / Introdução: A técnica de lipoaspiração recebeu várias contribuições desde sua primeira descrição, como modificações nas cânulas, variação na concentração da solução de infiltração e uso de aparelhos com tecnologias variadas. A utilização de aparelhos com tecnologia laser vem contribuir com o procedimento por meio da lipólise e com o estímulo de retração cutânea. Neste artigo é apresentada a experiência dos autores com a laserlipólise em 400 pacientes, no intervalo de 5 anos, sendo discutidos aspectos dos princípios da tecnologia e sua ação sobre os tecidos. Método: Estudo realizado entre julho de 2007 e julho de 2012, que incluiu 400 pacientes submetidos a procedimento de laserlipólise. Os procedimentos foram realizados seguindo protocolo original, com infiltração de soro gelado, passagem da cânula com fibra óptica para a condução da energia laser visando à laserlipólise, retração cutânea e, por último, lipoaspiração convencional. Resultados: O período de internação variou de cirurgia em regime ambulatorial a pernoite. Cerca de 45% (180/400 pacientes) dos pacientes evoluíram com equimoses mínimas, com acometimento de 2% ou mais da superfície corporal comprometida. Os casos de hematoma, seroma e deiscência totalizaram 9% (36/400 pacientes). Em nenhum caso foi constatada queimadura por lesão térmica na pele. Conclusões: O procedimento de laserlipólise realizado com a técnica descrita demonstrou segurança e reprodutibilidade

Studies have suggested the possibility that there is sensory (SS) afferent signaling from white adipose tissue (WAT) to the brain, which may play an important role in communication with the brain sympathetic nervous system (SNS) outflow to WAT. Therefore, we tested whether the SNS-SS feedback loop between the subcutaneous inguinal WAT (IWAT) and the epididymal WAT (EWAT) exists. These fat pads were chosen due to 1) their divergent role in manifestation of metabolic disorders with the IWAT being beneficial and the EWAT being detrimental, as well as 2) different lipolytic response to glucoprivic 2-deoxyglucose (2DG). By using retrograde tract tracers Fast Blue (FB) and Fluorogold (FG), we found that the IWAT is more innervated than EWAT by both the SS and SNS ganglia (T13-L3). Surprisingly, we found ~12-17% of double-labeled cells in the SNS and SS ganglia innervating fat depots, implying SNS-SS crosstalk loops between the IWAT and EWAT. Increased neuronal activation by 2DG was observed in the SNS ganglia to both IWAT and EWAT but not in the SS dorsal root ganglia. In addition, 2DG induced lipolysis in both fat pads with greater lipolytic properties in the IWAT as a result of higher density of the SNS-SS fibers. Collectively, our results show neuroanatomical reality of the IWAT and EWAT SNS-SS neural crosstalk with a coordinated control of lipolytic function.

Les aldose réductases (AKR1B) sont des oxydoréductases dépendantes du NADPH initialement décrites pour leurs fonctions de détoxication cellulaire et de réduction du glucose. La découverte de l’expression d’Akr1b7 dans le tissu adipeux murin ainsi que l’activité prostaglandine F2α synthase (PGFS) spécifique de certaines isoformes suggèrent des rôles biologiques inédits pour ces enzymes. La prostaglandine F2α (PGF2α) inhibant l’adipogenèse, cette fonction PGFS met en avant l’implication des AKR1B dans la physiologie du tissu adipeux blanc (TAB). L’objectif de ces travaux était de caractériser l’expression de l’ensemble des AKR1B au sein des TAB murins et humains et de comprendre leur impact sur l’homéostasie du tissu adipeux et en particulier sur l’adipogenèse et la lipolyse. Nous avons montré que l’ensemble des AKR1B était exprimé dans le TAB murin. Akr1b3, Akr1b8 et Akr1b16 sont exprimées à la fois dans les fractions stroma‑vasculaires (contenant des cellules immunitaires, vasculaires, progénitrices…) et adipocytaires. A l’inverse, Akr1b7 n’est pas exprimé par les adipocytes. Les analyses réalisées in vitro indiquent qu’à l’exception d’Akr1b16, les isoformes murines des AKR1B voient leur expression augmenter précocement et transitoirement au cours de l’adipogenèse. Chez l’homme, l’isoforme AKR1B1 est exprimée dans le TAB sous‑cutané de patients obèses alors qu’AKR1B10 est difficilement détectable (western blot, RT‑qPCR). In vitro, l’expression d’AKR1B1 augmente tout au long de la différenciation adipocytaire contrairement à AKR1B10 qui est préférentiellement exprimé dans les cellules indifférenciées. L’utilisation d’un inhibiteur spécifique des AKR1B montre que l’activité PGFS d’AKR1B1 constitue un frein à l’adipogenèse. Nous montrons aussi que les mécanismes régulant l’action de la PGF2α diffèrent en fonction des espèces. Chez l’homme, l’expression du récepteur FP est régulée dans le temps alors que dans les cellules murines, c’est l’expression des PGFS et donc la synthèse de PGF2α qui définit, au cours de l’adipogenèse, la fenêtre d’action de cette prostaglandine. Les souris invalidées pour la PGFS Akr1b7 présentent une diminution des quantités intra‑tissulaires en PGF2α associée à une expansion accrue de leurs tissus adipeux due à une augmentation de l’adipogenèse et à une hypertrophie adipocytaire sans modification de l’expression des enzymes impliquées dans la lipogenèse (Volat et al., 2012). Ces données en accord avec le rôle anti‑adipogénique de la PGF2α suggèrent aussi une action sur la lipolyse. Nous démontrons ici que la perte d’Akr1b7 entraîne une diminution de l’activité lipolytique du TAB. L’utilisation de cellules murines (3T3‑L1) et humaines (hMADS) différenciées en adipocytes, nous a permis de montrer que la stimulation de l’activité lipolytique suite à l’activation du récepteur FP résultait en partie d’une augmentation de la phosphorylation de HSL (forme active) et de l’accumulation de la lipase ATGL. Le troisième volet de ce travail de thèse a consisté à caractériser un modèle de souris transgénique surexprimant AKR1B1 dans le TAB (souris aP2‑AKR1B1) afin d’étudier le rôle biologique de cette isoforme humaine. / Aldose reductases are NADPH-dependent oxydoreductases described for their involvement in cellular detoxification and glucose reduction. The discovery of Akr1b7 expression in murine adipose tissue together with the prostaglandin F2α Synthase (PGFS) activity of some isoforms suggest unreleased biological roles for these enzymes. Prostaglandin F2α (PGF2α) inhibiting adipogenesis, this PGFS function highlights AKR1B potential involvement in white adipose tissue (WAT) physiology. This work aimed at characterising the expression of all AKR1B in both murine and human WAT and understanding their impact on adipose tissue homeostasis and especially on adipogenesis and lipolysis. We showed that all AKR1B were expressed in murine WAT. Akr1b3, Akr1b8 and Akr1b16 were both expressed in the stromal vascular fraction (containing immune cells, vascular cells, progenitors…) and in the adipose fraction. In contrast, Akr1b7 was not expressed in adipocytes. In vitro analyses indicated that, except for Akr1b16, murine AKR1B isoform expression increased early and transiently during adipogenesis. In human, AKR1B1 was expressed in human subcutaneous WAT from obese patients whereas AKR1B10 was hardly detectable (western blot, RT‑qPCR). In vitro, AKR1B1 expression increased throughout adipocyte differentiation unlike AKR1B10, which was preferentially expressed in undifferentiated cells. Using an AKR1B specific inhibitor, we demonstrated that AKR1B1 PGFS activity was a dampen to adipogenesis. We also showed that mechanisms regulating PGF2α action differed according to the species. In human cells, the expression of FP receptor was time-regulated whereas, in murine cells, PGFS expression and thus, PGF2α synthesis, limited PGF2α activity during adipogenesis. Akr1b7 knockout mice have decreased PGF2α intratissular levels associated with an expansion of adipose tissue resulting from an increase of adipogenesis and an adipocyte hypertrophia without any modification of lipogenic enzymes expression (Volat et al., 2012). These data, in agreement with PGF2α anti-adipogenic action, suggest an impact on lipolysis. We demonstrated that loss of Akr1b7 led to a decrease of WAT lipolytic activity. The use of murine (3T3‑L1) and human (hMADS) differentiated cells allowed us to show that the stimulation of lipolysis in response to FP activation was, in part, due to an increase of HSL phosphorylation (active form) and an increase of ATGL accumulation. The third part of this work consisted in characterizing the phenotype of transgenic mice overexpressing AKR1B1 in WAT (aP2‑AKR1B1 mice) in order to study the biological role of this human isoform.

Dados recentes apontam para a participação do sistema renina-angiotensina (SRA) em processos metabólicos, devido a sua presença local em tecidos metabolicamente ativos, como o tecido adiposo, e sugerem que tais tecidos também poderiam ser alvos dos bloqueadores do SRA. Por isso, investigamos possíveis efeitos diretos de bloqueadores do SRA no metabolismo celular de adipócitos isolados. Para isso, adipócitos isolados foram tratados com doses não tóxicas de Alisquireno ou Captopril ou Losartan. Após 24 horas, as capacidades lipolíticas, lipogênicas e oxidativas foram. Como resultados, o fármaco Alisquireno, aumentou a relação entre oxidação de glicose e incorporação desse substrato em lipídeos, enquanto o Captopril diminuiu a incorporação de glicose em lipídeos, particularmente na fração glicerol do TAG mediante estímulo com insulina, bem como diminuiu a expressão gênica de receptor de (pró) renina. Como conclusão, os fármacos Captopril e Alisquireno podem modular o metabolismo lipogênico e oxidativo de adipócitos isolados, mas de maneiras diferentes. / Recent data indicate a participation of the renina-angiotensin system (RAS) in metabolic process, due its local presence in tissues, like the adipose tissue, and suggests that these tissues could be targets of RAS blockers. Therefore, we have studied the possible effects of pharmacological RAS blockers in isolated fat cells. Therefore, fat cells were isolated of epididymal fat pad and treated with non toxic doses of Aliskiren or Captopril or Losartan. After 24 hours, the lipolytic, lipogenic and oxidative capacity were tested in their respective spontaneous and stimulated states. Also, gene expression of PPARg and RAS components were verified. The results showed Aliskiren increases the relation between oxidation and lipogenesis from glucose, whereas Captopril decreased glucose lipid incorporation, especially in glicerol fraction of triglyceride when insulin stimulus exist, and the Renin receptor gene expression. As a conclusion, Captopril and Aliskiren can directly modulate lipogenic and oxidative metabolism of isolated fat cells, but in a different way.