Angiotensin II and human obesity. A narrative review of the pathogenesis / Angiotensina II y obesidad humana. Revisión narrativa de la patogénesis

Abstract Angiotensin II (Ang II) is a hormone and the main effector of the renin-angiotensin system (RAS). This peptide has crucial pathophysiological effects on hypertension, cardiac hypertrophy, endothelial proliferation, inflammation and tissue remodelling through G protein-coupled receptors. The pro-inflammatory role of Ang II has been reported in various inflammatory processes. Obesity is linked to a chronic inflammatory process which in turn is the cause of some of its morbidities. Ang II is related to the comorbidities related to the comorbidities of obesity, which include alterations in the heart, kidney, hypertension and coagulation. In this regard, activation of AT1 receptors by Ang II can induce an inflammatory process mediated by the transcription factor NF-kB, triggering inflammation in various systems that are related to the comorbidities observed in obesity. The aim of this review was to highlight the pro-inflammatory effects of Ang II and the alterations induced by this hormone in various organs and systems in obesity. The search was done since 1990 through Medline, EMBASE and PubMed, using the keywords: angiotensin II; angiotensin II, obesity; angiotensin II, kidney, obesity; angiotensin II, coagulation, obesity; angiotensin II, inflammation, obesity; angiotensin II, adipose tissue, obesity; angiotensin II, hypertension, obesity; angiotensin II, insulin resistance, obesity; angiotensin II, adiponectin, leptin, obesity; angiotensin II, COVID-19, obesity. Angiotensin II through its interaction with its AT1 receptor, can induce alterations in diverse systems that are related to the comorbidities observed in obesity. Therapeutic strategies to decrease the production and action of Ang II could improve the clinical conditions in individuals with obesity.

Resumen La angiotensina II (Ang II) es una hormona y el principal efector del sistema renina-angiotensina (SRA). Este péptido tiene importantes efectos fisiopatológicos en la hipertensión, la hipertrofia cardíaca, la proliferación endotelial, la inflamación y la remodelación tisular a través de receptores acoplados a la proteína G. El papel pro-inflamatorio de la Ang II se ha reportado en diversos procesos inflamatorios. La obesidad está ligada a un proceso inflamatorio crónico que a su vez es causa de algunas de sus morbilidades. Se ha demostrado que la Ang II está relacionada con las comorbilidades de la obesidad, que incluyen alteraciones en el corazón, el riñón, la hipertensión y la coagulación. En este sentido, la activación de los receptores AT1 por la Ang II puede inducir un proceso inflamatorio mediado por el factor de transcripción NFkB desencadenado inflamación en diversos sistemas que se relacionan con las co-morbilidades observadas en la obesidad. El propósito de esta revisión fue destacar el efecto pro-inflamatorio de la Ang II y las alteraciones inducidas por esta hormona en diversos órganos y sistemas en la obesidad. La búsqueda se hizo desde 1990 a través de Medline, EMBASE and PubMed, utilizando las palabras clave: angiotensina II; angiotensina II, obesidad; angiotensina II, riñón, obesidad; angiotensina II, coagulación, obesidad; angiotensina II, inflamación, obesidad; angiotensin II, adipose tissue, obesidad; angiotensin II, hipertensión, obesidad; angiotensin II, resistencia a la insulina, obesidad; angiotensin II, adiponectina, leptina, obesidad; angiotensina II, COVID-19, obesidad. La angiotensina II a través de su interacción con su receptor AT1 puede inducir alteraciones en diversos sistemas que están relacionados con las comorbilidades observadas en la obesidad. Estrategias terapeúticas para disminuir su producción y la acción de la AngII pudieran mejorar las condiciones clínicas en individuos con obesidad.

Increased C-reactive protein and decreased Interleukin-2 content in serum from obese individuals with or without insulin resistance: Associations with leukocyte count and insulin and adiponectin content.

AIMS: Chronic inflammation in obesity is associated with co-morbidities such as, hyperglycemia, hypertension and hyperlipidemia. Leukocytes play an important role in this inflammation and C-reactive protein (CRP) and Interleukin-2 (IL-2) can be important effectors during the immune response in obesity; however, the initial inflammatory events in obesity remain unclear. The aim of this study was to determine the circulating levels of CRP, IL-2, insulin and adiponectin, their association and the association with leukocyte count in obese individuals without co-morbidities and with or without insulin resistance (IR). MATERIALS AND METHODS: Nineteen obese non-diabetic and 9 lean subjects were studied for serum levels of CRP, IL-2, insulin, adiponectin, lipids, glycated hemoglobin, glycemia, for homeostasis model assessment of insulin resistance (HOMA-IR), arterial pressure and anthropometric parameters, and for leukocyte counts. Neutrophil/lymphocyte ratio (N/L) was calculated using the loge of leukocyte counts. Associations were determined by Pearson's correlation. RESULTS: None of the studied groups presented co-morbidities and two groups of obese individuals with normal or high levels of insulin (IR) were found. Increased CRP concentration and decreased IL-2 and adiponectin concentrations in obese were observed. Positive correlation between leukocyte type counts with CRP in obese with IR was found; however, no correlations with IL-2 in obese were observed. Insulin in obese were positively correlated with CRP and negatively correlated with IL-2 in IR obese individuals. Adiponectin in obese was negatively correlated with CRP. CONCLUSION: CRP and IL-2 may represent two important effectors in the early inflammatory events in obese individuals without co-morbidities. Adiponectin and insulin may be involved in anti-inflammatory events.

[Reflections in our 55th anniversary]. / Reflexiones en nuestro 55to. Aniversario.

Investigación Clínica has been published uninterruptedly for 55 years and for this reason, the University of Zulia has recognized the work of its editorial team with the imposition of the Order "Jesus Enrique Lossada". Despite some financial and structural problems we are optimistic because our journal has been included in new international indices and it is connected to the scientific world through the contributions from all continents; by the selfless collaboration of hundreds of domestic and foreign referees who respond with great professionalism; and through the visits to our website, from virtually around the world. Reviewing the SCImago statistical analysis, we found that among the Venezuelan medical journals, Investigación Clínica is first in cites per document (2 years) and second in the H index, and compares favorably with prestigious Latin-American journals. It is noteworthy that both in Venezuela and beyond our borders, the submission of topic reviews has increased in detriment of original papers or contributions. It seems that the lack of financial support to research institutes and universities, has led to a decline in experimental projects, at least in the medical field that occupies this journal, so researchers resort to reviews in their respective fields, as a compensation to maintain their productivity. This has caused that the Editorial Board has limited the reception of reviews to keep intact the percentage of published original contributions. Finally, we would like to think that there are no obstacles that can not be overcome to maintain our excellence in publishing Investigación Clínica.

Increased proinflammatory markers and lipoperoxidation in obese individuals: Inicial inflammatory events?

BACKGROUND: Chronic inflammation associated to obesity increases the risk for developing insulin resistance (IR), hyperglycemia, hypertension and hyperlipidemia. The initial factors involved in generating the inflammatory events in the obesity remain unclear. Therefore, this study was aimed to determine inflammatory and oxidative markers in the blood of obese individuals with normal clinical and biochemical parameters and with or without IR. METHODS: Nineteen obese non-diabetic and nine lean subjects were studied for serum levels of TNF-α, IL-1ß, adiponectin, angiotensin II, insulin, malondialdehyde (MDA) and the expressions of RAGE (advanced glycation end product receptor), AT1 (Ang II receptor), s100A12 protein (RAGE ligand) and nuclear factor-κB (NF-κB) in circulating mononuclear cells (CMC) by available antibodies and commercial kits. CMC were also cultured to determine pro-inflammatory mediators. RESULTS: Insulin was increased in obese subjects with IR. Decreased serum adiponectin in obese individuals and increased TNF-α, IL-1ß and CMC bearing RAGE, AT1 and s100A12 in obese individuals without IR were found. High values of serum MDA in obese subjects were observed. Similar TNF-content in cultures from obese and controls, increased cellular IL-1ß content in cultures from obese individuals without IR and high content of MDA in supernatants from obese individual cultures were observed. CONCLUSIONS: The inflammatory events were mainly observed in obese individuals without IR. The absent of inflammatory events and high levels of insulin in obese subjects with IR, suggest a protector role of insulin for developing inflammatory events. These data can represent initial aspects of the chronic inflammation observed in the obesity.

Association of obesity with leukocyte count in obese individuals without metabolic syndrome.

AIMS: Inflammation in obesity is associated to insulin resistance (IR), hyperglycemia, hypertension and hyperlipidemia. Leukocytes play an important role in obesity associated inflammation. The initial factors that generate the inflammatory events in the obesity remain unclear. Therefore, the aim of this study was to determine the association of circulating leukocytes with clinical and biochemical parameters in obese individuals with clinical and biochemical parameters in normal range and with or without IR. METHODS: Nineteen obese non-diabetic and 9 lean subjects were studied for serum levels of insulin, lipids, glycated hemoglobin, glycemia, for clinical parameters as HOMA-IR, arterial pressure and anthropometric parameters, and for leukocyte counts. Neutrophil/lymphocyte ratio (N/L) was calculated using the loge of leukocyte counts. Association between leukocytes and studied parameters was determined by Pearson's correlation. RESULTS: Two groups of obese individuals were observed: with high levels of insulin (with IR) and with normal levels (without IR). Positive correlations were observed between leukocyte and lymphocyte counts with body mass index and HOMA-IR and negative correlation with decreased HDL levels. Lymphocytes correlated with increased levels of insulin. Leukocytes and neutrophils correlated positively with increased visceral fat and liver steatosis. These associations were absent in the obese group without IR. N/L ratio did not show correlations with studied parameters. The leukocyte associations were mainly observed in obese individuals with IR. CONCLUSIONS: These data may represent initial leukocyte associations with morbidity features and define two different obese individuals that may evolve to the chronic inflammation observed in the obesity.

[Increasing difficulties for scientific publication in Venezuela]. / Aumentan las dificultades para la publicación científica en Venezuela.

A very important increase in the costs of the edition of scientific journals has taken place in Venezuela, due to difficulties in obtaining imported free acid paper and other materials used for handling documents. Like other journals, Investigaci6n Clinica has been considering switching completely to a digital publication format; however there are several reasons that prevent us to doing it at this time: the journal is distributed in printed form to many national institutions, which do not have immediate access to digital information. In addition, there exists a commitment of shipment of printed issues for some international indices and in exchange with other national and foreign journals, whose printed format we receive. Another important aspect is that our University maintains a weak technological platform that makes difficult the immediacy required for the interchange with authors and consulted referees of received papers; and there is a latent danger of limitations in the use of digital technologies, due to current national politic problems. Consequently, we need to continue with the printed format, but must reduce the amount of printed issues, so as not to limit the number of papers published in each edition. Nevertheless, there is an ever increasing number of contributions from foreign researches and Investigaci6n Clinica has been recently included in two new international indices, the SEIIC from Argentina and the Infobase Index from India, reasons that obligate us to maintain our levels of excellence and commitment to our authors and readers.

[Hepatic steatosis, visceral fat and metabolic alterations in apparently healthy overweight/obese individuals]. / Esteatosis hepática, grasa visceral y alteraciones metabólicas, en individuos con sobrepeso/obesidad aparentemente sanos.

Clinical observation indicates that many obese individuals do not display important metabolic alterations. Consequently, the objective of this study was to establish whether simple obesity, non concurrent with other important risk factors, was associated with metabolic alterations; or if the phenomenon known as "obesity paradox" was present. A clinical history, measurements of anthropometric and metabolic parameters and estimation of hepatic steatosis and visceral fat, were determined in 30, apparently healthy, individuals from Maracaibo, Venezuela, between 20 and 59 years of age and a body mass index (BMI) above 25 kg/m2, and compared to a lean control group of 11 individuals with BMI less than 25 kg/m2. The study demonstrated that only one third of overweight/obese individuals (OW/OB), with high body mass index (BMI) and waist circumference (WC), presented elevated values of insulin, HOMA-IR and triglycerides. Nevertheless, the presence of hepatic steatosis was elevated in the OW/OB group (91%) vs. 9% in the control group. The visceral fat in the lean control group was associated with both, WC and glycemia; however, it was not related to the BMI or insulin, HOMA-IR and HDLc. The visceral fat in the OW/OB group, although elevated in relation to the lean group, revealed a loss of these associations. In the OW/OB it was the BMI that was associated with insulin and HOMA-IR. The results emphasize the importance of investigating for the presence of hepatic steatosis, rather than visceral fat, in individuals with OW/OB, to identify subjects with high cardiometabolic risk.

Esteatosis hepática, grasa visceral y alteraciones metabólicas, en individuos con sobrepeso/obesidad aparentemente sanos / Hepatic steatosis, visceral fat and metabolic alterations in apparently healthy overweight/obese individuals

La observación clínica indica que muchos obesos no presentan alteraciones metabólicas importantes, por lo que el objetivo del presente estudio fue comprobar si el sobrepeso/obesidad (SP/OB) simple, no asociado a otros factores de riesgo, se acompañaba de alteraciones metabólicas; o si estaba presente el fenómeno conocido como “paradoja de la obesidad”. A 30 individuos aparentemente sanos de Maracaibo, Venezuela, entre 20 y 59 años de edad, e índice de masa corporal (IMC) superior a 25 kg/m², y a un grupo control de 11 individuos con IMC inferior a 25 kg/m², se les realizó una historia clínica, medida de parámetros antropométricos, determinaciones basales de glicemia, insulina y lípidos, medición ultrasonográfica para esteatosis hepática y ultrasonografía e impedancia bioeléctrica para estimar la grasa visceral. El estudio demostró que solo en un tercio de los individuos con SP/OB, con elevado IMC y circunferencia de cintura (CC), se encontraron concentraciones elevadas de insulina, HOMA-IR y triglicéridos. A pesar de ello, la presencia de esteatosis hepática fue muy elevada (91%) en el grupo SP/OB, si se compara con 9% en el grupo control. La grasa visceral, en el grupo control, estuvo asociada a la CC y a la glicemia; sin embargo, no se relacionó con el IMC, insulina, HOMA-IR o HDLc; mientras que en el grupo SP/OB, aunque estadísticamente elevada en relación al grupo control, reveló una pérdida de estas asociaciones. Los resultados resaltan la importancia de investigar más la presencia de esteatosis hepática en los individuos con SP/OB, que la estimación de la grasa visceral, para identificar sujetos con alto riesgo cardiometabólico.

Clinical observation indicates that many obese individuals do not display important metabolic alterations. Consequently, the objective of this study was to establish whether simple obesity, non concurrent with other important risk factors, was associated with metabolic alterations; or if the phenomenon known as “obesity paradox” was present. A clinical history, measurements of anthropometric and metabolic parameters and estimation of hepatic steatosis and visceral fat, were determined in 30, apparently healthy, individuals from Maracaibo, Venezuela, between 20 and 59 years of age and a body mass index (BMI) above 25 kg/m²,and compared to a lean control group of 11 individuals with BMI less than 25 kg/m². The study demonstrated that only one third of overweight/obese individuals (OW/OB), with high body mass index (BMI) and waist circumference (WC), presented elevated values of insulin, HOMA-IR and triglycerides. Nevertheless, the presence of hepatic steatosis was elevated in the OW/OB group (91%) vs. 9% in the control group. The visceral fat in the lean control group was associated with both, WC and glycemia; however, it was not related to the BMI or insulin, HOMA-IR and HDLc. The visceral fat in the OW/OB group, although elevated in relation to the lean group, revealed a loss of these associations. In the OW/OB it was the BMI that was associated with insulin and HOMA-IR. The results emphasize the importance of investigating for the presence of hepatic steatosis, rather than visceral fat, in individuals with OW/OB, to identify subjects with high cardiometabolic risk.

[Fate of the results of research projects]. / Destino de los resultados de los proyectos de investigación.

Once completed, the results of a research project must be made known to the scientific community. This is usually achieved by presentations at scientific meetings or by publishing the results in a journal of the specialty. The purpose is not only to make public these findings, but that they can be used to solve problems, immediately or in the long-term, or to serve as the basis for future research. However, several studies have found that less than 50% of the communications to congresses are published. One of the main reasons is that publications in high impact journals can not be easily attained since most of them are not of open access. For this reason, it is convenient to resort to free-access journals listed in prestigious international indexes. The Council for Scientific Development at the University of Zulia financially supports a number of scientific journals that meet these criteria. If the research was the result of a PhD, Master or Specialty thesis or the project for a promotion in an academic institution, the end result should be also their publication; but commonly, these are even less published than communications to scientific meetings. At the University of Zulia, Serbiluz has made a major effort to collect all this material and make it available to serve the scientific community. It is necessary to mention that the institution that supports financially a research project has the right to demand its publication, to benefit the greatest number of people and as a mean to compensate the economic support with scientific knowledge.

[Overcoming difficulties is our goal in 2011]. / Superar las dificultades es nuestra meta en el 2011.

During the past two years, Investigación Clínica has undergone a substantial reduction in its funding caused by the insufficient budget allotment that the University of Zulia has received from the Venezuelan Government. The progressive increase in the number of articles contained in each issue of the journal caused its weight to exceed the established limits, affecting the distribution costs. Therefore, some adjustments to its structure and distribution are required to maintain its frequency and quality, including reducing the number of papers per issue and sacrificing free shipping to many libraries and health centers in our country and abroad. The "Instructions to Authors" will appear only in the first issue and we will keep the "Index of Authors" in the last issue of the year. Also the publishing of reprints will be limited and only will be sent to authors upon request and shipment pre-payment. Likewise, color pages fees will be canceled to the Publishers, prior to printing. For the above mentioned difficulties, we recommend our regular readers to use the website https://sites.google.com/site/revistainvestigacionesclinicas/, where all articles can be found in PDF format, as they appear in our printed edition. Despite these difficulties, all our collaborators will keep working to maintain the high standards that have characterized this journal for over 50 years, inspired by our founder, Dr. Américo Negrette.

["Investigación Clínica": 50 years disseminating biomedical research]. / "Investigación Clínica": 50 años divulgando investigación biomédica.

INVESTIGACION CLINICA was founded by the initiative of Américo Negrette, who became its first editor, and it has been published uninterruptedly since July 1960, with a quarterly frequency. The first issues consisted mainly of a collection of reviews of seminars held at the now called Instituto de Investigaciones Clínicas "Dr. Américo Negrette", Facultad de Medicina, Universidad del Zulia, its publisher. Very soon, original research results from this institution were included in the novel journal. In the 60's, papers on results obtained during the outbreaks of Venezuelan Equine Encephalitis present in the area, were prominent. Originally, the journal published 3-4 papers, but due to the increased number of contributions, in 2001, its format changed from 1/16 to 1/8, and now each number includes 11 original articles. Currently, INVESTIGACION CLINICA publishes 44 papers a year, in Spanish or English on different biomedical topics, from contributors all around the world. Progressively it has been included in different renowned indexes, such as PubMed/MEDLINE, Science Citation Index Expanded, Excerpta Medica, Tropical Diseases Bulletin, Copernicus, Scopus, Periodica, and several others. Besides, it can be found in open access through www.Scielo.org.ve, www.freemedicaljournals.com and in our new Web page: https://sites. google.com/site/revistainvestigacionesclinicas/home. Most papers published in INVESTIGACION CLINICA have been cited in the regional or foreign literature accumulating more than 1200 citations by now. For this particular issue, to celebrate the 50th anniversary of INVESTIGACION CLINICA, we have invited some of our more recent referees or authors to contribute with Reviews in their respective areas of expertise.

Association of free fatty acids with the insulin-resistant state but not with central obesity in individuals from Venezuela.

Individuals with insulin resistance (IR) usually have upper body obesity phenotype, often accompanied by an increase in plasma free fatty acids (FFA). Since the Venezuelan population has a high frequency of IR and central obesity, the purpose of this work was to determine FFA levels in 47 Venezuelan individuals, men and women, 24-58 years old, and analyze their relationship with central obesity and parameters of carbohydrate and lipid metabolism. Basal concentrations of TG, total cholesterol, LDL-C, and HDL-C were measured, and FFA, glucose and insulin, at basal state and at different times after a glucose load. Eighteen individuals presented insulin resistance (HOMA-IR > 2.7) and 29 were non-insulin resistant (non-IR). Insulin resistant individuals (IR) had higher waist circumference, BMI and basal concentrations of FFA than the non-IR. No differences were observed in skin folds and other basal lipids studied. The increased FFA seemed to be related to the IR associated to BMI and not to central obesity, since the difference between IR and non-IR disappeared when they were matched for waist circumference. After a glucose load, FFA decreased in both groups, but remained significantly elevated in IR subjects. This effect disappeared after matching for BMI or waist circumference, inferring that it was independent of anthropometries. FFA were positively associated with HOMA-IR, glucose and TG levels; however, there was.no association with BMI or waist circumference. These findings, and the lack of elements to support the presence of hepatic IR, common to increased visceral lipolysis, might suggest that the IR present in the obese individuals studied, might be due to an increase in subcutaneous fat.

Medición ultrasonográfica de grasa visceral intraabdominal en hombres obesos: Asociación con alteración de lípidos séricos e insulinemia / Ultrasonography measurement of intrabdominal visceral fat in obese men: Association with alterations in serum lipids and insulinemia

La obesidad abdominal, por la adiposidad intraabdominal, conduce a progresión de factores de riesgos cardiometabólicos independientemente del índice de masa corporal. En este trabajo se evaluaron 154 hombres, entre 20 y 60 años de edad, que acudieron a examen anual preventivo de salud laboral en Venezuela. Se utilizó el ultrasonido para establecer la presencia y medición de grasa visceral. La grasa visceral se asoció en forma positiva y significativa con la edad, la circunferencia abdominal y el HOMA-IR tanto en los normopeso como en los de sobrepeso y obeso mientras que con el IMC solo se obtuvo correlación en los normopeso y sobrepeso. En los obesos se observó correlación positiva entre la grasa visceral con la glucemia y los triglicéridos. Con la insulina solo se encontró correlación en los individuos de peso normal. Los valores de grasa visceral se incrementaron con el paso de normopeso-sobrepeso-obeso. Con base a las curvas ROC y tomando como punto de corte para la grasa visceral un valor de 6 cm, se podría predecir hiperglucemia con un 58,6% de sensibilidad y 77% de especificidad; insulino-resistencia con 54% de sensibilidad y 78% de especificidad; hipertrigliceridemia con 39% de sensibilidad y 78% de especificidad y bajo HDLc con 45% de sensibilidad y 77 % de especificidad. El área debajo de la curva en el análisis de ROC fue mayor para la grasa visceral comparado con la circunferencia abdominal para la hiperglucemia (0,727 vs 0,693, p< 0,05) mientras que lo contrario se observó para HOMA-IR (0,74 vs 0,788, p<0,05) y para el HDLc bajo (0,651 vs 0,668, p<0,05). Así la grasa visceral, determinada por ultrasonido, resultó mejor predictor de alteraciones de la glicemia y los triglicéridos, mientras que la circunferencia abdominal sería mejor para predecir alteraciones como insulina resistencia y bajo HDLc, por lo que se sugiere su inclusión en la valoración preventiva de pacientes para determinación de alteraciones metabólicas.

Abdominal obesity and specifically intrabdominal adiposity leads to increase in cardiometabolic risk factors (CMR), independently of body mass index (BMI). In order to examine CMR factors associated with the presence of visceral fat (VF) in individuals with different degrees of overweight/obesity, 154 men, 20 to 60 years of age, attending a at an Industrial Clinic in Venezuela, were evaluated. Ultrasound was used to establish the presence and amount of VF. As expected, VF values were higher as the BMI increased. It was observed that VF was associated positive and significantly with age, abdominal circumference and the degree of insulin resistance (HOMA-IR) in subjects with normal weight as well as in those with overweight and obesity. However, BMI was correlated with VF only in those with normal weight or overweight. In the obese a positive correlation was observed between VF with glycemia and triglycerides, while insulin was correlated with VF only in the subjects with normal weight. Based on the ROC curves, and taking as cut-off point for VF a value of 6 cm, it was possible to predict the presence of hyperglycemia with a 58.6% of sensitivity and 77% of specificity, presence of insulin resistance with 54 % of sensitivity and 78 % specificity, hypertriglyceridemia with 39% of sensitivity and 78% specificity and low HDLc with 45% sensitivity and 77% specificity. The area under the curve for the ROC analysis was greater for visceral fat compared with abdominal circumference for hyperglicemia (0.727 vs. 0.693, p< 0.05) while the opposite was observed for HOMA-IR (0.74 vs. 0.788, p<0.05) and for low HDL-c (0.651 vs. 0.668, p<0.05). We conclude that ultrasound measure of VF, was better in predicting hyperglycemia and hypertriglyceridemia, while abdominal circumference was better predicting insulin resistance and low HDLc and could be useful in the preventive evaluation of individuals at risk for diabetes or cardiovascular disease.

Association of free fatty acids with the insulin-resistant state but not with central obesity in individuals from Venezuela

Individuals with insulin resistance (IR) usually have upper body obesity phenotype, often accompanied by an increase in plasma free fatty acids (FFA). Since the Venezuelan population has a high frequency of IR and central obesity, the purpose of this work was to determine FFA levels in 47 Venezuelan individuals, men and women, 24-58 years old, and analyze their relationship with central obesity and parameters of carbohydrate and lipid metabolism. Basal concentrations of TG, total cholesterol, LDL-C, and HDL-C were measured, and FFA, glucose and insulin, at basal state and at different times after a glucose load. Eighteen individuals presented insulin resistance (HOMA-IR >2.7) and 29 were non-insulin resistant (non-IR). Insulin resistant individuals (IR) had higher waist circumference, BMI and basal concentrations of FFA than the non-IR. No differences were observed in skin folds and other basal lipids studied. The increased FFA seemed to be related to the IR associated to BMI and not to central obesity, since the difference between IR and non-IR disappeared when they were matched for waist circumference. After a glucose load, FFA decreased in both groups, but remained significantly elevated in IR subjects. This effect disappeared after matching for BMI or waist circumference, inferring that it was independent of anthropometrics. FFA were positively associated with HOMA-IR, glucose and TG levels; however, there was no association with BMI or waist circumference. These findings, and the lack of elements to support the presence of hepatic IR, common to increased visceral lipolysis, might suggest that the IR present in the obese individuals studied, might be due to an increase in subcutaneous fat.

Los individuos con insulino-resistencia (IR) usualmente presentan obesidad central, fenotipo comúnmente acompañado de incremento de ácidos grasos libres (AGL). Como los individuos venezolanos presentan una alta frecuencia de IR y obesidad central, el objetivo de este trabajo fue analizar, en un grupo de ellos, la relación entre AGL y obesidad central y parámetros relacionados con el metabolismo de carbohidratos y lípidos. En 47 venezolanos, hombres y mujeres, entre 24 y 58 años, se determinaron las concentraciones basales de TG, Colesterol total, LDL-C, HDL-C y AGL, glucemia e insulina a nivel basal y a diferentes tiempos después de una sobrecarga glucosada. Dieciocho individuos resultaron IR (HOMA-IR > 2,7) y 29 no IR. Los IR presentaron mayor circunferencia de cintura (CC), índice de masa corporal (IMC) y concentraciones basales de AGL. No hubo diferencias en los pliegues cutáneos ni en los otros lípidos. Los valores elevados de AGL parecieron relacionarse con la IR asociada al IMC y no a la obesidad central puesto que una vez apareados por CC, la diferencia en los valores de AGL entre IR y no-IR desapareció. Después de la sobrecarga glucosada los AGL disminuyeron en ambos grupos, pero permanecieron significativamente elevados en los IR. Esta diferencia desapareció al aparear por IMC o CC. Los AGL estuvieron significativamente asociados a HOMA-IR, glucemia y TG, sin embargo no se encontró asociación con IMC o CC. Estos hallazgos, más la falta de elementos que apoyen la presencia de IR hepática, común en un incremento de la lipólisis visceral, sugieren que la IR presente en estos individuos obesos pueda ser debida a incremento de la grasa subcutánea.