Miriam H. Fonseca-Alaniz

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 centro regulador do metabolismo

The recent progress in the research about the metabolic properties of the adipose tissue and the discovery of its ability to produce hormones that are very active in pathophysiologic as well as physiologic processes is rebuilding the concepts about its biology. Its involvement in conditions like obesity, type 2 diabetes mellitus, arterial hypertension, arteriosclerosis, dislipidemias and chronic and acute inflammatory processes indicate that the understanding of its functional capacities may contribute to improve the prognosis of those diseases whose prevalence increased in a preoccupying manner. Here we review some functional aspects of adipocytes, such as the metabolism, its influence on energy homeostasis, its endocrine ability and the adipogenesis, i.e., the potential of pre-adipocytes present in adipose tissue stroma to differentiate into new adipocytes and regenerate the tissue. In addition, we are including some studies on the relationship between the adipose tissue and the pineal gland, a new and poorly known, although, as will be seen, very promising aspect of adipocyte physiology together with its possible favorable repercussions to the therapy of the obesity related diseases.

O tecido adiposo como órgão endócrino: da teoria à prática

OBJETIVOS Mostrar os avancos na pesquisa sobre o papel fisiologico do tecido adiposo branco, ressaltando o seu papel endocrino em processos inflamatorios, no comportamento alimentar, na sensibilizacao a insulina e na modulacao do processo de aterogenese. Abordar o potencial papel do tecido adiposo como fonte de celulas-tronco para regeneracao de tecidos, com especial enfase para a adipogenese e suas consequencias para a geracao de obesidade. FONTES DE DADOS: Informacoes importantes constantes da literatura cientifica foram compiladas de modo a que esta leitura contenha uma sintese esclarecedora dos aspectos mencionados acima. SINTESE DOS DADOS:O tecido adiposo possui, alem das suas funcoes classicas como principal estoque de energia metabolica, suprindo as necessidades energeticas em periodos de carencia mediante a lipolise, a capacidade de sintetizar e secretar varios hormonios, as adipocinas. Estas agem em diversos processos, como o controle da ingestao alimentar (leptina) e o controle da sensibilidade a insulina e de processos inflamatorios (TNF-alfa, IL-6, resistina, visfatina, adiponectina). Alem disso, como o tecido adiposo contem tambem celulas indiferenciadas, tem a habilidade de gerar novos adipocitos, regenerando o proprio tecido (adipogenese), bem como originar outras celulas (mioblastos, condroblastos, osteoblastos), fato este que tem grande potencial terapeutico em futuro nao muito distante. CONCLUSAO: Amplia-se o leque de possibilidades funcionais do tecido adiposo. A compreensao dessas potencialidades pode fazer deste tecido o grande aliado no combate de molestias que atualmente vem assumindo proporcoes epidemicas (obesidade, diabetes melito, hipertensao arterial e arteriosclerose), nas quais o tecido adiposo ainda e tido como um grande vilao. 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.

High dietary sodium intake increases white adipose tissue mass and plasma leptin in rats.

Objective: Salt restriction has been reported to increase white adipose tissue (WAT) mass in rodents. The objective of this study was to investigate the effect of different sodium content diets on the lipogenic and lipolytic activities of WAT.

The role of inflamed adipose tissue in the insulin resistance.

In this article, we discuss inflammation associated with adipose tissue dysfunction as a potential link with obesity‐related insulin resistance, and how obesity‐related inflammatory components, such as immune cells, cytokines/chemokines and adipocytokines, induce obesity‐related pathologies. Copyright

Leucine supplementation improves adiponectin and total cholesterol concentrations despite the lack of changes in adiposity or glucose homeostasis in rats previously exposed to a high-fat diet.

BackgroundStudies suggest that leucine supplementation (LS) has a therapeutic potential to prevent obesity and to promote glucose homeostasis. Furthermore, regular physical exercise is a widely accepted strategy for body weight maintenance and also for the prevention of obesity. The aim of this study was to determine the effect of chronic LS alone or combined with endurance training (ET) as potential approaches for reversing the insulin resistance and obesity induced by a high-fat diet (HFD) in rats.MethodsForty-seven rats were randomly divided into two groups. Animals were fed a control diet-low fat (n = 10) or HFD (n = 37). After 15 weeks on HFD, all rats received the control diet-low fat and were randomly divided according to treatment: reference (REF), LS, ET, and LS+ET (n = 7-8 rats per group). After 6 weeks of treatment, the animals were sacrificed and body composition, fat cell volume, and serum concentrations of total cholesterol, HDL-cholesterol, triacylglycerol, glucose, adiponectin, leptin and tumor necrosis factor-alpha (TNF-α) were analyzed.ResultsAt the end of the sixth week of treatment, there was no significant difference in body weight between the REF, LS, ET and LS+ET groups. However, ET increased lean body mass in rats (P = 0.019). In addition, ET was more effective than LS in reducing adiposity (P = 0.019), serum insulin (P = 0.022) and TNF-α (P = 0.044). Conversely, LS increased serum adiponectin (P = 0.021) levels and reduced serum total cholesterol concentration (P = 0.042).ConclusionsThe results showed that LS had no beneficial effects on insulin sensitivity or adiposity in previously obese rats. On the other hand, LS was effective in increasing adiponectin levels and in reducing total cholesterol concentration.

Reduced lipolysis and increased lipogenesis in adipose tissue from pinealectomized rats adapted to training

Abstract:  The current study investigated the effects of chronic training and pinealectomy on the lipogenic and lipolytic activity of adipose tissue. Pinealectomized and sham‐operated adult male Wistar rats were distributed in to four subgroups: pinealectomized untrained, pinealectomized trained, control untrained and control trained. At the end of the training period (8 wk) the rats were killed. Blood samples were collected for glucose, insulin and leptin determinations. Peri‐epididymal adipocytes were isolated for measurement of in vitro rates of lipolysis and incorporation of substrates (d‐[U‐14C]‐glucose, l‐[U‐14C]‐lactate, [2‐14C]‐acetate and [1‐14C]‐palmitate) into lipids, and samples of epididymal adipose tissue were homogenized for evaluation of glucose‐6‐phosphate dehydrogenase maximal activity. Pinealectomy resulted in a significantly increased lipolytic capacity in response to isoproterenol and a decrease in circulating leptin levels without affecting the rates of incorporation of different substrates into lipids. However, only in the intact control group did training promote a higher basal and isoproterenol‐stimulated lipolysis, increase the incorporation of palmitate (esterification), decrease the incorporation of acetate (lipogenesis) into lipids and diminish circulating leptin levels. These effects of exercise training were not seen in pinealectomized rats. However, pinealectomized trained animals showed a marked reduction in lipolysis and an increased rate of acetate incorporation. In conclusion, we demonstrated for the first time that the pineal gland plays an important role in the regulation of lipid metabolism in such a way that its absence caused a severe alteration in the balance between lipogenesis and lipolysis, which becomes evident with the adaptation to exercise training.

Dipeptidyl peptidase IV inhibition upregulates GLUT4 translocation and expression in heart and skeletal muscle of spontaneously hypertensive rats.

The purpose of the current study was to test the hypothesis that the dipeptidyl peptidase IV (DPPIV) inhibitor sitagliptin, which exerts anti-hyperglycemic and anti-hypertensive effects, upregulates GLUT4 translocation, protein levels, and/or mRNA expression in heart and skeletal muscle of spontaneously hypertensive rats (SHRs). Ten days of treatment with sitagliptin (40 mg/kg twice daily) decreased plasma DPPIV activity in both young (Y, 5-week-old) and adult (A, 20-week-old) SHRs to similar extents (~85%). However, DPPIV inhibition only lowered blood pressure in Y-SHRs (119 ± 3 vs. 136 ± 4 mmHg). GLUT4 translocation, total protein levels and mRNA expression were decreased in the heart, soleus and gastrocnemius muscle of SHRs compared to age-matched Wistar Kyoto (WKY) normotensive rats. These differences were much more pronounced between A-SHRs and A-WKY rats than between Y-SHRs and Y-WKY rats. In Y-SHRs, sitagliptin normalized GLUT4 expression in the heart, soleus and gastrocnemius. In A-SHRs, sitagliptin increased GLUT4 expression to levels that were even higher than those of A-WKY rats. Sitagliptin enhanced the circulating levels of the DPPIV substrate glucagon-like peptide-1 (GLP-1) in SHRs. In addition, stimulation of the GLP-1 receptor in cardiomyocytes isolated from SHRs increased the protein level of GLUT4 by 154 ± 13%. Collectively, these results indicate that DPPIV inhibition upregulates GLUT4 in heart and skeletal muscle of SHRs. The underlying mechanism of sitagliptin-induced upregulation of GLUT4 in SHRs may be, at least partially, attributed to GLP-1.

High Sodium Intake Enhances Insulin‐stimulated Glucose Uptake in Rat Epididymal Adipose Tissue

Objective: This study investigated the effect of different sodium content diets on rat adipose tissue carbohydrate metabolism and insulin sensitivity.

Metabolic recovery of adipose tissue is associated with improvement in insulin resistance in a model of experimental diabetes.

Obesity and insulin resistance are highly correlated with metabolic disturbances. Both the excess and lack of adipose tissue can lead to severe insulin resistance and diabetes. Adipose tissue plays an active role in energy homeostasis, hormone secretion, and other proteins that affect insulin sensitivity, appetite, energy balance, and lipid metabolism. Rats with streptozotocin-induced diabetes during the neonatal period develop the classic diabetic picture of hyperglycemia, hypoinsulinemia, and insulin resistance in adulthood. Low body weight and reduced epididymal (EP) fat mass were also seen in this model. The aim of this study was to investigate the glucose homeostasis and metabolic repercussions on the adipose tissue following chronic treatment with antidiabetic drugs in these animals. In the 4th week post birth, diabetic animals started an 8-week treatment with pioglitazone, metformin, or insulin. Animals were then killed, EP fat pads were excised, and blood samples were collected for biological and biochemical assays. Pioglitazone and insulin treatments, but not metformin, reduced hyperglycemia, polydipsia, and polyphagia. Although all antidiabetic therapies improved insulin sensitivity, this was particularly noteworthy in the pioglitazone-treated rats. Furthermore, a recovery of adipose mass and insulin levels were observed in pioglitazone- and insulin-, but not metformin-treated animals. Treatments with insulin or pioglitazone were able to correct significantly, but not completely, the metabolic abnormalities, parallel to full recovery of adipose mass, indicating that not only the low insulin levels but also the lack of adipose tissue might play a significant role on the pathophysiology of this particular diabetes model.