Ginkgo biloba Extract Stimulates Adipogenesis in 3T3-L1 Preadipocytes.

Smaller adipocytes are related to the reversal of metabolic disorders, suggesting that molecules that can act in the adipogenesis pathway are of great interest. The objective of this study was to investigate the effect of Ginkgo biloba extract (GbE) in modulating the differentiation in preadipocytes. 3T3-L1 preadipocytes were differentiated for 7 days into adipocytes without (control group) and with GbE at 1.0 mg/mL. Lipid content and gene expression were analyzed on day 7 (D7) by Oil Red O staining and PCR Array Gene Expression. Western blotting analysis of the key adipogenesis markers was evaluated during the differentiation process at days 3 (D3), 5 (D5), and 7 (D7). GbE increased lipid content and raised the gene expression of the main adipogenesis markers. Key proteins of the differentiation process were modulated by GbE, since C/EBPß levels were decreased, while C/EBPα levels were increased at D7. Regarding the mature adipocytes' markers, GbE enhanced the levels of both FABP4 at D5, and perilipin at D3 and D5. In summary, the present findings showed that GbE modulated the adipogenesis pathway suggesting that the treatment could accelerate the preadipocyte maturation, stimulating the expression of mature adipocyte proteins earlier than expected.

Omega-3 Polyunsaturated Fatty Acids Prevent Nonalcoholic Steatohepatitis (NASH) and Stimulate Adipogenesis.

The increasing impact of obesity on global human health intensifies the importance of studies focusing on agents interfering with the metabolism and remodeling not only of the white adipose tissue (WAT) but also of the liver. In the present study, we have addressed the impact of n-3 PUFA in adipose cells' proliferation and adipogenesis, as well as in the hepatic lipid profile and morphology. Mice were induced to obesity by the consumption of a high-fat diet (HFD) for 16 weeks. At the 9th week, the treatment with fish oil (FO) was initiated and maintained until the end of the period. The FO treatment reduced the animals' body mass, plasma lipids, glucose, plasma transaminases, liver mass, triacylglycerol, and cholesterol liver content when compared to animals consuming only HFD. FO also decreased the inguinal (ing) WAT mass, reduced adipocyte volume, increased adipose cellularity (hyperplasia), and increased the proliferation of adipose-derived stromal cells (AdSCs) which corroborates the increment in the proliferation of 3T3-L1 pre-adipocytes or AdSCs treated in vitro with n-3 PUFA. After submitting the in vitro treated (n-3 PUFA) cells, 3T3-L1 and AdSCs, to an adipogenic cocktail, there was an increase in the mRNA expression of adipogenic transcriptional factors and other late adipocyte markers, as well as an increase in lipid accumulation when compared to not treated cells. Finally, the expression of browning-related genes was also higher in the n-3 PUFA treated group. We conclude that n-3 PUFA exerts an attenuating effect on body mass, dyslipidemia, and hepatic steatosis induced by HFD. FO treatment led to decreasing adiposity and adipocyte hypertrophy in ingWAT while increasing hyperplasia. Data suggest that FO treatment might induce recruitment (by increased proliferation and differentiation) of new adipocytes (white and/or beige) to the ingWAT, which is fundamental for the healthy expansion of WAT.

Obesity and covid-19: a reflection on the relationship between pandemics.

OBJECTIVE: Carry out a reflective analysis on the relationship of obesity as a risk factor for the worsening of COVID-19. METHOD: Reflective study, supported by scientific evidence, which contributed to a critical-reflexive construction on the theme "Obesity" in interface with "Covid-19". RESULTS: This study brought up important reflections for health professionals, researchers and managers, from the beginning of the pandemic, a period in which obesity was not recognized as a risk factor, until the current scenario, in which a series of pathophysiological mechanisms that clinically connect these diseases are being proposed. CONCLUSION: Obesity is a risk factor for the worsening of COVID-19, which is contributing to the overload of health services, and which requires differentiated health care, with adjustments in care, pharmacological protocols and commitment to health education in the within the Unified Health System.

Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism.

Obesity is linked with altered microbial short-chain fatty acids (SCFAs), which are a signature of gut dysbiosis and inflammation. In the present study, we investigated whether tributyrin, a prodrug of the SCFA butyrate, could improve metabolic and inflammatory profiles in diet-induced obese mice. Mice fed a high-fat diet for eight weeks were treated with tributyrin or placebo for another six weeks. We show that obese mice treated with tributyrin had lower body weight gain and an improved insulin responsiveness and glucose metabolism, partly via reduced hepatic triglycerides content. Additionally, tributyrin induced an anti-inflammatory state in the adipose tissue by reduction of Il-1ß and Tnf-a and increased Il-10, Tregs cells and M2-macrophages. Moreover, improvement in glucose metabolism and reduction of fat inflammatory states associated with tributyrin treatment were dependent on GPR109A activation. Our results indicate that exogenous targeting of SCFA butyrate attenuates metabolic and inflammatory dysfunction, highlighting a potentially novel approach to tackle obesity.

Melatonin Supplementation Decreases Hypertrophic Obesity and Inflammation Induced by High-Fat Diet in Mice.

Obesity results from critical periods of positive energy balance characterized by caloric intake greater than energy expenditure. This disbalance promotes adipose tissue dysfunction which is related to other comorbidities. Melatonin is a low-cost therapeutic agent and studies indicate that its use may improve obesity-related disorders. To evaluate if the melatonin is efficient in delaying or even blocking the damages caused by excessive ingestion of a high-fat diet (HFD) in mice, as well as improving the inflammatory profile triggered by obesity herein, male C57BL/6 mice of 8 weeks were induced to obesity by a HFD and treated for 10 weeks with melatonin. The results demonstrate that melatonin supplementation attenuated serum triglyceride levels and total and LDL cholesterol and prevented body mass gain through a decreased lipogenesis rate and increased lipolytic capacity in white adipocytes, with a concomitant increment in oxygen consumption and Pgc1a and Prdm16 expression. Altogether, these effects prevented adipocyte hypertrophy caused by HFD and reflected in decreased adiposity. Finally, melatonin supplementation reduced the crown-like-structure (CLS) formation, characteristic of the inflammatory process by macrophage infiltration into white adipose tissue of obese subjects, as well as decreased the gene expression of inflammation-related factors, such as leptin and MCP1. Thus, the melatonin can be considered a potential therapeutic agent to attenuate the metabolic and inflammatory disorders triggered by obesity.

Melatonin Supplementation Attenuates the Pro-Inflammatory Adipokines Expression in Visceral Fat from Obese Mice Induced by A High-Fat Diet.

Obesity is defined as a condition of abnormal or excessive fat accumulation in white adipose tissue that results from the exacerbated consumption of calories associated with low energy expenditure. Fat accumulation in both adipose tissue and other organs contributes to a systemic inflammation leading to the development of metabolic disorders such as type 2 diabetes, hypertension, and dyslipidemia. Melatonin is a potent antioxidant and improves inflammatory processes and energy metabolism. Using male mice fed a high-fat diet (HFD-59% fat from lard and soybean oil; 9:1) as an obesity model, we investigated the effects of melatonin supplementation on the prevention of obesity-associated complications through an analysis of plasma biochemical profile, body and fat depots mass, adipocytes size and inflammatory cytokines expression in epididymal (EPI) adipose depot. Melatonin prevented a gain of body weight and fat depot mass as well as adipocyte hypertrophy. Melatonin also reversed the increase of total cholesterol, triglycerides and LDL-cholesterol. In addition, this neurohormone was effective in completely decreasing the inflammatory cytokines leptin and resistin in plasma. In the EPI depot, melatonin reversed the increase of leptin, Il-6, Mcp-1 and Tnf-α triggered by obesity. These data allow us to infer that melatonin presents an anti-obesity effect since it acts to prevent the progression of pro-inflammatory markers in the epididymal adipose tissue together with a reduction in adiposity.

Microenvironmental stimuli induce different macrophage polarizations in experimental models of emphysema.

Macrophages play a pivotal role in the development of emphysema and depending on the microenvironment stimuli can be polarized into M1- or M2-like macrophage phenotypes. We compared macrophage polarizations in cigarette smoke (CS)- and porcine pancreatic elastase (PPE)-induced emphysema models. C57BL/6 mice were subdivided into four experimental groups. In the PPE group, animals received an intranasal instillation of PPE (0.677 IU); in the saline group, animals received an intranasal instillation of saline (0.9%). Animals from both groups were euthanized on day 28. In the CS group, animals were exposed to CS for 30 min, twice a day, 5 days per week for 12 weeks. In the control group, animals received filtered air. We observed an increase in total macrophages for both experimental models. For M1-like macrophage markers, we observed an increase in TNF-α+ and IFN-γ+ cells, Cxcl-9 and Cxcl-10 expressions in PPE and CS groups. Only in the CS group, we detected an increased expression of IL-12b For M2-like macrophages markers we observed a down regulation in IL-10, IL-4, IL-13, Arg1 and Fizz1 and an increase of TGF-ß+ cells in the PPE group, while for the CS group there was an increase in TGF-ß+ cells and IL-10 expression. All exposure groups were compared to their respective controls. In summary, we demonstrated that CS- and PPE-induced models resulted in different microenvironmental stimuli. CS exposure induced an environmental stimulus related to M1- and M2-like macrophage phenotypes similar to previous results described in COPD patients, whereas the elastase-induced model provided an environmental stimulus related only to the M1 phenotype.

Protective Effects of Anti-IL17 on Acute Lung Injury Induced by LPS in Mice.

Introduction: T helper 17 (Th17) has been implicated in a variety of inflammatory lung and immune system diseases. However, little is known about the expression and biological role of IL-17 in acute lung injury (ALI). We investigated the mechanisms involved in the effect of anti-IL17 in a model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Methods: Mice were pre-treated with anti-IL17, 1h before saline/LPS intratracheal administration alongside non-treated controls and levels of exhaled nitric oxide (eNO), cytokine expression, extracellular matrix remodeling and oxidative stress, as well as immune cell counts in bronchoalveolar lavage fluid (BALF), and respiratory mechanics were assessed in lung tissue. Results: LPS instillation led to an increase in multiple cytokines, proteases, nuclear factor-κB, and Forkhead box P3 (FOXP3), eNO and regulators of the actomyosin cytoskeleton, the number of CD4+ and iNOS-positive cells as well as the number of neutrophils and macrophages in BALF, resistance and elastance of the respiratory system, ARG-1 gene expression, collagen fibers, and actin and 8-iso-PGF2α volume fractions. Pre-treatment with anti-IL17 led to a significant reduction in the level of all assessed factors. Conclusions: Anti-IL17 can protect the lungs from the inflammatory effects of LPS-induced ALI, primarily mediated by the reduced expression of cytokines and oxidative stress. This suggests that further studies using anti-IL17 in a treatment regime would be highly worthwhile.

Combination of a high-fat diet with sweetened condensed milk exacerbates inflammation and insulin resistance induced by each separately in mice.

Obesogenic diets increase body weight and cause insulin resistance (IR), however, the association of these changes with the main macronutrient in the diet remains to be elucidated. Male C57BL/6 mice were fed with: control (CD), CD and sweetened condensed milk (HS), high-fat (HF), and HF and condensed milk (HSHF). After 2 months, increased body weight, glucose intolerance, adipocyte size and cholesterol levels were observed. As compared with CD, HS ingested the same amount of calories whereas HF and HSHF ingested less. HS had increased plasma AST activity and liver type I collagen. HF caused mild liver steatosis and hepatocellular damage. HF and HSHF increased LDL-cholesterol, hepatocyte and adipocyte hypertrophy, TNF-α by macrophages and decreased lipogenesis and adiponectin in adipose tissue (AT). HSHF exacerbated these effects, increasing IR, lipolysis, mRNA expression of F4/80 and leptin in AT, Tlr-4 in soleus muscle and IL-6, IL-1ß, VCAM-1, and ICAM-1 protein in AT. The three obesogenic diets induced obesity and metabolic dysfunction. HS was more proinflammatory than the HF and induced hepatic fibrosis. The HF was more detrimental in terms of insulin sensitivity, and it caused liver steatosis. The combination HSHF exacerbated the effects of each separately on insulin resistance and AT inflammatory state.

Effects of Anti-IL-17 on Inflammation, Remodeling, and Oxidative Stress in an Experimental Model of Asthma Exacerbated by LPS.

Inflammation plays a central role in the development of asthma, which is considered an allergic disease with a classic Th2 inflammatory profile. However, cytokine IL-17 has been examined to better understand the pathophysiology of this disease. Severe asthmatic patients experience frequent exacerbations, leading to infection, and subsequently show altered levels of inflammation that are unlikely to be due to the Th2 immune response alone. This study estimates the effects of anti-IL-17 therapy in the pulmonary parenchyma in a murine asthma model exacerbated by LPS. BALB/c mice were sensitized with intraperitoneal ovalbumin and repeatedly exposed to inhalation with ovalbumin, followed by treatment with or without anti-IL-17. Twenty-four hours prior to the end of the 29-day experimental protocol, the two groups received LPS (0.1 mg/ml intratracheal OVA-LPS and OVA-LPS IL-17). We subsequently evaluated bronchoalveolar lavage fluid, performed a lung tissue morphometric analysis, and measured IL-6 gene expression. OVA-LPS-treated animals treated with anti-IL-17 showed decreased pulmonary inflammation, edema, oxidative stress, and extracellular matrix remodeling compared to the non-treated OVA and OVA-LPS groups (p < 0.05). The anti-IL-17 treatment also decreased the numbers of dendritic cells, FOXP3, NF-κB, and Rho kinase 1- and 2-positive cells compared to the non-treated OVA and OVA-LPS groups (p < 0.05). In conclusion, these data suggest that inhibition of IL-17 is a promising therapeutic avenue, even in exacerbated asthmatic patients, and significantly contributes to the control of Th1/Th2/Th17 inflammation, chemokine expression, extracellular matrix remodeling, and oxidative stress in a murine experimental asthma model exacerbated by LPS.

[Control of adipogenesis by fatty acids]. / Controle da adipogênese por ácidos graxos.

Obesity is one of the major Public Health problems. Obese individuals are more susceptible to develop cardiovascular diseases and type 2 diabetes mellitus. The obesity results from the increase in size and number of the adipocytes. The balance between adipogenesis and adiposity determines the degree of obesity. Mature adipocytes secrete adipokines, such as TNFalpha, IL-6, leptine and adiponectin, and lipokine, the palmitoleic acid omega-7. The production of adipokines is increased in obesity, contributing to the onset of peripheral insulin resistance. The knowledge about the molecular events that regulate the differentiation of pre-adipocytes and mesenchymal stem cells into adipocytes (adipogenesis) is important for the comprehension of the genesis of obesity. Activation of transcription factor PPARgamma plays an essential role in the adipogenesis. Certain fatty acids are PPARgamma ligands and can control adipogenesis. Moreover, some fatty acids act as signaling molecules regulating their differentiation into adipocytes or death. Accordingly, the lipid composition of the diet and PPARgamma agonists can regulate the balance between adipogenesis and death of adipocytes and, therefore, the obesity.

Adipocyte differentiation is inhibited by melatonin through the regulation of C/EBPbeta transcriptional activity.

Considering that melatonin has been implicated in body weight control, this work investigated whether this effect involves the regulation of adipogenesis. 3T3-L1 preadipocytes were induced to differentiate in the absence or presence of melatonin (10(-3) m). Swiss-3T3 cells ectopically and conditionally (Tet-off system) over-expressing the 34 kDa C/EBPbeta isoform (Swiss-LAP cells) were employed as a tool to assess the mechanisms of action at the molecular level. Protein markers of the adipogenic phenotype were analyzed by Western blot. At 36 hr of differentiation of 3T3-L1 preadipocytes, a reduction of PPARgamma expression was detected followed by a further reduction, at day 4, of perilipin, aP2 and adiponectin protein expression in melatonin-treated cells. Real-time PCR analysis also showed a decrease of PPARgamma (60%), C/EBPalpha (75%), adiponectin (30%) and aP2 (40%) mRNA expression. Finally, we transfected Swiss LAP cells with a C/EBPalpha gene promoter/reporter construct in which luciferase expression is enhanced in response to C/EBPbeta activity. Culture of such transfected cells in the absence of tetracycline led to a 2.5-fold activation of the C/EBPalpha promoter. However, when treated with melatonin, the level of C/EBPalpha promoter activation by C/EBPbeta was reduced by 50% (P = 0.05, n = 6). In addition, this inhibitory effect of melatonin was also reflected in the phenotype of the cells, since their capacity to accumulate lipids droplets was reduced as confirmed by the poor staining with Oil Red O. In conclusion, melatonin at a concentration of 10(-3 ) m works as a negative regulator of adipogenesis acting in part by inhibiting the activity of a critical adipogenic transcription factor, C/EBPbeta.

Controle da adipogênese por ácidos graxos: [revisão] / Control of adipogenesis by fatty acids: [review]

A obesidade é um dos principais problemas de saúde pública. Indivíduos obesos são mais suscetíveis a desenvolver doenças cardiovasculares e diabetes melito tipo 2. A obesidade resulta do aumento no tamanho e no número de adipócitos. O balanço entre adipogênese e adiposidade determina o grau de obesidade do indivíduo. Adipócitos maduros secretam adipocinas, tais como TNFα, IL-6, leptina e adiponectina, e lipocina, o ácido palmitoleico ω-7. A produção de adipocinas é maior na obesidade, o que contribui para o estabelecimento de resistência periférica à insulina. O conhecimento dos eventos moleculares que regulam a diferenciação dos pré-adipócitos e de células-tronco mesenquimais em adipócitos (adipogênese) é importante para o entendimento da gênese da obesidade. A ativação do fator de transcrição PPARγ é essencial na adipogênese. Certos ácidos graxos são ligantes de PPARγ e podem, assim, controlar a adipogênese. Além disso, alguns ácidos graxos atuam como moléculas sinalizadoras em adipócitos, regulando sua diferenciação ou morte. Dessa forma, a composição lipídica da dieta e os agonistas de PPARγ podem regular o balanço entre adipogênese e morte de adipócitos e, portanto, a obesidade.

Obesity is one of the major Public Health problems. Obese individuals are more susceptible to develop cardiovascular diseases and type 2 diabetes mellitus. The obesity results from the increase in size and number of the adipocytes. The balance between adipogenesis and adiposity determines the degree of obesity. Mature adipocytes secrete adipokines, such as TNFα, IL-6, leptine and adiponectin, and lipokine, the palmitoleic acid ω-7. The production of adipokines is increased in obesity, contributing to the onset of peripheral insulin resistance. The knowledge about the molecular events that regulate the differentiation of pre-adipocytes and mesenchymal stem cells into adipocytes (adipogenesis) is important for the comprehension of the genesis of obesity. Activation of transcription factor PPARγ plays an essential role in the adipogenesis. Certain fatty acids are PPARγ ligands and can control adipogenesis. Moreover, some fatty acids act as signaling molecules regulating their differentiation into adipocytes or death. Accordingly, the lipid composition of the diet and PPARγ agonists can regulate the balance between adipogenesis and death of adipocytes and, therefore, the obesity.

Melatonin and the circadian entrainment of metabolic and hormonal activities in primary isolated adipocytes.

The aim of this work was to investigate the effect of the in vitro circadian-like exposure to melatonin [in the presence or absence of insulin (Ins)] on the metabolism and clock gene expression in adipocytes. To simulate the cyclic characteristics of the daily melatonin profile, isolated rat adipocytes were exposed in a circadian-like pattern to melatonin added to the incubating medium for 12 hr (mimicking the night), followed by an equal period without melatonin (mimicking the day) combined or not with Ins. This intermittent incubation was interrupted when four and a half 24-hr cycles were fulfilled. At the end, either during the induced night (melatonin present) or the induced day (melatonin absent), the rates of lipolysis and D-[U-(14)C]-glucose incorporation into lipids were estimated, in addition to the determination of lipogenic [glucose-6-phosphate dehydrogenase and fatty acid synthase (FAS)] and lipolytic (hormone sensitive lipase) enzymes and clock gene (Bmal-1b, Clock, Per-1 and Cry-1) mRNA expression. The leptin release was also measured. During the induced night, the following effects were observed: an increase in the mRNA expression of Clock, Per-1 and FAS; a rise in lipogenic response and leptin secretion; and a decrease in the lipolytic activity. The intermittent exposure of adipocytes to melatonin temporally and rhythmically synchronized their metabolic and hormonal function in a circadian fashion, mimicking what is observed in vivo in animals during the daily light-dark cycle. Therefore, this work helps to clarify the physiological relevance of the circadian pattern of melatonin secretion and its interactions with Ins, contributing to a better understanding of the adipocyte biology.

Adipose tissue as an endocrine organ: from theory to practice.

OBJECTIVE: To describe the advances in research into the physiological role of white adipose tissue, with emphasis on its endocrinal role in inflammatory processes, feeding behavior, insulin sensitization and modulation of the atherogenetic process. To deal with the potential role of adipose tissue as a source of stem cells for regeneration of tissues, with special emphasis on adipogenesis and its consequences for development of obesity. SOURCES: Important information was compiled from the scientific literature in order that this analysis contains an explanatory synthesis of the aspects mentioned above. SUMMARY OF THE FINDINGS In addition to its classical functions as primary metabolic energy store, meeting energy requirements during periods of deprivation by means of lypolisis, adipose tissue also has the capacity to synthesize and secrete a variety of hormones - the adipokines. These are active in a range of processes, such as control of nutritional intake (leptin) and control of sensitivity to insulin and inflammatory processes (TNF-alpha, IL-6, resistin, visfatin, adiponectin). Furthermore, since adipose tissue also contains undifferentiated cells, it has the ability to generate new adipocytes, regenerating its own tissue (adipogenesis), and also the ability to give rise to other cells (myoblasts, chondroblasts, osteoblasts), which has great therapeutic potential in the not-too-distant future. CONCLUSIONS: The range of functional possibilities of adipose tissue has widened. An understanding of these potentials could make this tissue a great ally in the fight against conditions that are currently assuming epidemic proportions (obesity, diabetes mellitus, arterial hypertension and arteriosclerosis) and in which adipose tissue is still seen as the enemy.

O tecido adiposo como órgão endócrino: da teoria à prática: [revisão] / Adipose tissue as an endocrine organ: from theory to practice: [review]

OBJETIVOS Mostrar os avanços na pesquisa sobre o papel fisiológico do tecido adiposo branco, ressaltando o seu papel endócrino em processos inflamatórios, no comportamento alimentar, na sensibilização à insulina e na modulação do processo de aterogênese. Abordar o potencial papel do tecido adiposo como fonte de células-tronco para regeneração de tecidos, com especial ênfase para a adipogênese e suas conseqüências para a geração de obesidade. FONTES DE DADOS: Informações importantes constantes da literatura científica foram compiladas de modo a que esta leitura contenha uma síntese esclarecedora dos aspectos mencionados acima. SÍNTESE DOS DADOS:O tecido adiposo possui, além das suas funções clássicas como principal estoque de energia metabólica, suprindo as necessidades energéticas em períodos de carência mediante a lipólise, a capacidade de sintetizar e secretar vários hormônios, as adipocinas. Estas agem em diversos processos, como o controle da ingestão alimentar (leptina) e o controle da sensibilidade à insulina e de processos inflamatórios (TNF-alfa, IL-6, resistina, visfatina, adiponectina). Além disso, como o tecido adiposo contém também células indiferenciadas, tem a habilidade de gerar novos adipócitos, regenerando o próprio tecido (adipogênese), bem como originar outras células (mioblastos, condroblastos, osteoblastos), fato este que tem grande potencial terapêutico em futuro não muito distante. CONCLUSÃO: Amplia-se o leque de possibilidades funcionais do tecido adiposo. A compreensão dessas potencialidades pode fazer deste tecido o grande aliado no combate de moléstias que atualmente vêm assumindo proporções epidêmicas (obesidade, diabetes melito, hipertensão arterial e arteriosclerose), nas quais o tecido adiposo ainda é tido como um grande vilão.

OBJECTIVES: To describe the advances in research into the physiological role of white adipose tissue, with emphasis on its endocrinal role in inflammatory processes, feeding behavior, insulin sensitization and modulation of the atherogenetic process. To deal with the potential role of adipose tissue as a source of stem cells for regeneration of tissues, with special emphasis on adipogenesis and its consequences for development of obesity. SOURCES: Important information was compiled from the scientific literature in order that this analysis contains an explanatory synthesis of the aspects mentioned above. SUMMARY OF THE FINDINGS In addition to its classical functions as primary metabolic energy store, meeting energy requirements during periods of deprivation by means of lypolisis, adipose tissue also has the capacity to synthesize and secrete a variety of hormones - the adipokines. These are active in a range of processes, such as control of nutritional intake (leptin) and control of sensitivity to insulin and inflammatory processes (TNF-alpha, IL-6, resistin, visfatin, adiponectin). Furthermore, since adipose tissue also contains undifferentiated cells, it has the ability to generate new adipocytes, regenerating its own tissue (adipogenesis), and also the ability to give rise to other cells (myoblasts, chondroblasts, osteoblasts), which has great therapeutic potential in the not-too-distant future. CONCLUSIONS: The range of functional possibilities of adipose tissue has widened. An understanding of these potentials could make this tissue a great ally in the fight against conditions that are currently assuming epidemic proportions (obesity, diabetes mellitus, arterial hypertension and arteriosclerosis) and in which adipose tissue is still seen as the enemy.

Pinealectomy reduces hepatic and muscular glycogen content and attenuates aerobic power adaptability in trained rats.

The current study emphasizes the crucial role of the pineal gland on the effects of chronic training in different tissues focusing on carbohydrate metabolism. We investigated the maximal oxygen uptake (aerobic power), muscle and liver glycogen content, and also the enzymes involved in the carbohydrate metabolism of rat adipose tissue. Pinealectomized and sham-operated adult male Wistar rats were distributed into four groups: pinealectomized (PINX) untrained, pinealectomized trained, control untrained and control trained. The maximal oxygen uptake capability was assayed before and after the training protocol by indirect open circuit calorimetry. The rats were killed after 8 wk of training. Blood samples were collected for glucose and insulin determinations. The glycogen content was assayed in the liver and muscle. Maximal activities of epididymal adipose tissue enzymes (hexokinase, pyruvate kinase, lactate dehydrogenase, citrate synthase and malic enzyme) as well as adipocyte size were determined. The exercise training in control animals promoted an increase in the aerobic power and in liver glycogen content but caused a reduction in the malic enzyme activity in adipose tissue. However, PINX trained animals, in contrast to trained controls, showed a decrease in the aerobic power and in liver and muscle glycogen content, as well as an increase in the activity of the adipocyte enzymes involved in carbohydrate metabolism. In conclusion, these data show that the pineal gland integrity is necessary for the homeostatic control of energy metabolism among adipose, muscle and hepatic tissues. The pinealectomized animals showed alterations in adaptive responses of the maximal oxygen uptake to training. Therefore, the pineal gland must be considered an influential participant in the complex adaptation to exercise and is involved in the improvement of endurance capacity.

Intermittent and rhythmic exposure to melatonin in primary cultured adipocytes enhances the insulin and dexamethasone effects on leptin expression.

Considering the cyclic characteristic of production and secretion of pineal melatonin, it is reasonable to assume that this oscillation might be important in determining the variety of its circadian and seasonal effects. To simulate this physiological condition in vitro, isolated adipocytes were exposed to melatonin in a circadian-like pattern by adding the hormone to the incubating medium during 12 hr (mimicking the night), followed by an equal period without melatonin (mimicking the day). This intermittent procedure was interrupted when three cycles with melatonin were fulfilled (60-hr incubation). Here, we report the effects of melatonin (1 nM) added intermittently or continuously to the incubating medium alone or in combination with insulin (5 nM) and/or dexamethasone (7 nM) on leptin release and expression by rat adipocytes. After acute 12-hr incubation neither melatonin nor insulin alone affected leptin expression, but together they increased it by 105%. Dexamethasone increased leptin mRNA content and release (70%) but this effect was not enhanced by melatonin. Nevertheless, after 60 hr under intermittent melatonin, we observed a synergism between melatonin and dexamethasone. This interaction promoted an increment (75% compared with dexamethasone alone) in leptin release and expression. Our results suggest that circadian-like exposure to melatonin potentiates the dexamethasone action and is important to the effects promoted by insulin on leptin expression. Based on an in vitro approach, this work helps to clarify the physiological relevance and the repercussions of the in vivo circadian pattern of melatonin secretion.

Melatonin enhances leptin expression by rat adipocytes in the presence of insulin.

Leptin and melatonin play an important role in the regulation of body mass and energy balance. Both hormones show a circadian rhythm, with increasing values at night. In addition, melatonin receptors were recently described in adipocytes, where leptin is synthesized. Here, we investigated the influence of melatonin and its interaction with insulin and dexamethasone on leptin expression. Isolated rat adipocytes were incubated with melatonin (1 nM) alone or in combination with insulin (5 nM) and/or dexamethasone (7 nM) for 6 h. Melatonin or insulin alone did not affect leptin expression, but together they increased it by 120%. Dexamethasone increased leptin mRNA content (105%), and this effect was not enhanced by melatonin. Simultaneous treatment with the three hormones provoked a further increase in leptin release (250%) and leptin mRNA (100%). Melatonin prevented the forskolin-induced inhibition (95%) of leptin expression. In addition, melatonin's ability to stimulate leptin release (in the presence of insulin) was completely blocked by pertussis toxin and luzindole. To gain further insight into the molecular basis of melatonin and insulin synergism, the insulin-signaling pathway was investigated. Melatonin increased the insulin-induced insulin receptor-beta tyrosine phosphorylation, which led to an increased serine phosphorylation of the downstream convergent protein Akt. We concluded that melatonin interacts with insulin and upregulates insulin-stimulated leptin expression. These effects are caused by melatonin binding to the pertussis toxin-sensitive G(i) protein-coupled membrane receptor (MT1 subtype) and the cross talk with insulin, since insulin receptor and its convergent target Akt are coactivated by melatonin.