Juan José Hernández-Morante

Relationship between fat cell size and number and fatty acid composition in adipose tissue from different fat depots in overweight/obese humans

Objective:To evaluate the body fat distribution and fat cell size and number in an overweight/obese population from both genders, and to determine the possible relationship between fat cell data from three different adipose tissue localizations (subcutaneous (SA), perivisceral and omental) and adipose tissue composition and dietary fatty acid.Design:The sample consisted of 84 overweight/obese patients (29 men and 55 women) who have undergone abdominal surgery. The adipocyte size and total fat cell number was studied. Fat cell data were related with anthropometric, adipose tissue and subjects habitual diet fatty acid composition.Measurements:Fat cell size was measured according to a Sjöström method from the three adipose depots. Total fat cell number was also calculated. The fatty acid composition of adipose tissue was examined by gas chromatography. The subjects diet was studied by a 7 days dietary record.Results:Our data showed a negative relationship between the adipocyte size and the n-6 and n-3 fatty acids content of the SA adipose tissue (r=−0.286, P=0,040; r=−0.300, P=0.030) respectively, and the n-6 in the omental depots (r=−0.407, P=0.049) in the total population. Positive associations with the total of saturated (r=0.357, P=0.045) and negative (r=−0.544, P=0.001) with the n-9 fatty acids were observed when the relationship between the adipocyte number and the fatty acid composition of the different anatomical fat regions was studied. Dietary fatty acids composition positively correlated with fat cell size for the myristic acid (14:0) in men in the visceral depot (r=0.822, P=0.023), and for the saturated fatty acids (SFAs) in women in the omental depot (r=0.486, P=0.035).Conclusion:In the present study, for the first time in humans we found that n-3 and n-6 fatty acids are related to a reduced adipocyte size according to the depot localization. In contrast, adipose tissue and dietary SFAs sinificantly correlated with an increase in fat cell size and number. No significant associations were found between n-9 acids content and adipocyte size. However, n-9 adipose tissue fatty acids content was inversely associated with fat cell number showing that this type of fatty acid could limit hyperplasia in obese populations. The differences observed in the three different regions, perivisceral, omental and SA fat, indicate that this population adipose tissue have depot-specific differences.

Clock genes are implicated in the human metabolic syndrome

Background:Clock genes play a role in adipose tissue (AT) in animal experimental models. However, it remains to be elucidated whether these genes are expressed in human AT.Objective:We investigated the expression of several clock genes, Bmal1, Per2 and Cry1, in human AT from visceral and subcutaneous abdominal depots. A second objective was to elucidate whether these clock genes expressions were related to the metabolic syndrome features.Methods:Visceral and subcutaneous AT samples were obtained from morbid obese men (n=8), age: 42±13 years and body mass index⩾40 kg/m2, undergoing laparoscopic surgery due to obesity. Biopsies were taken as paired samples at the beginning of the surgical process (1100 hour). Metabolic syndrome features such as waist circumference, plasma glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein (LDL) cholesterol were also studied. Homeostasis model assessment index of insulin resistance was also calculated. The expression of the different clock genes, hBmal1, hPer2 and hCry1, was determined by quantitative real-time PCR.Results:Clock genes were expressed in both human AT depots. hBmal1 expression was significantly lower than hPer2 and hCry1 in both AT (P<0.001). All genes were highly correlated to one another in the subcutaneous fat, while no correlation was found between Bmal1 and Per2 in the visceral AT. Clock genes AT expression was associated with the metabolic syndrome parameters: hPer2 expression level from visceral depot was inversely correlated to waist circumference (P<0.01), while the three clock genes studied were significantly and negatively correlated to total cholesterol and LDL cholesterol (P<0.01).Conclusion:We have demonstrated for the first time in humans that clock genes are expressed in both subcutaneous and visceral fat. Their association with abdominal fat content and cardiovascular risk factors may be an indicator of the potential role of these clock genes in the metabolic syndrome disturbances.

Circadian Rhythm of Clock Genes in Human Adipose Explants

To analyze in severely obese women the circadian expression of the clock genes hPer2, hBmal1, and hCry1 in explants from subcutaneous (SAT) and visceral (VAT) adipose tissue (AT), in order to elucidate whether this circadian clockwork can oscillate accurately and independently of the suprachiasmatic nucleus (SCN) and if glucocorticoid metabolism‐related genes such as glucocorticoid receptor (hGr) and 11β‐hydroxysteroid dehydrogenase 1 (h11βHsd1) and the transcription factor peroxisome proliferator activated receptor γ (hPPARγ) are part of the clock controlled genes. AT biopsies were obtained from morbid obese patients (BMI ≥40 kg/m2) (n = 7). Anthropometric variables were measured and fasting plasma lipids and lipoprotein concentrations were analyzed. In order to carry out rhythmic expression analysis, AT explants were cultured during 24 h and gene expression was performed at the following times (T): 0, 6, 12, and 18 h, with quantitative real‐time PCR. Clock genes oscillated accurately and independently of the SCN in AT explants. Their intrinsic oscillatory mechanism regulated the timing of other genes such as hPPARγ and glucocorticoid‐related genes. Circadian patterns differed between VAT and SAT. Correlation analyses between the genetic circadian oscillation and components of the metabolic syndrome (MetS) revealed that subjects with a higher sagittal diameter showed an increased circadian variability in hPer2 expression (r = 0.91; P = 0.031) and hBmal1 (r = 0.90; P = 0.040). Data demonstrate the presence of peripheral circadian oscillators in human AT independently of the central circadian control mechanism. This knowledge paves the way for a better understanding of the circadian contribution to medical conditions such as obesity and MetS.

Adiponectin, the controversial hormone

OBJECTIVE To discuss present knowledge about adiponectin hormone. DESIGN Review of existing literature. SETTING AND RESULTS Adiponectin is one of the most interesting cytokines associated with obesity, although its physiological role remains to be fully clarified. Adiponectin is a 247-amino acid protein that contains four differentiable domains. Contrary to most adipose-related cytokines, adiponectin levels are surprisingly lower in obese than in lean humans. Women have been found to have significantly higher adiponectin plasma concentrations than men. Further research is needed in order to identify new polymorphisms which contribute to explain the potential role of adiponectin in obesity and related pathologies. Considering the anti-inflammatory properties of adiponectin and the fact that it is negatively associated with adiposity, this cytokine could be one of the links between obesity and inflammation. The main mechanisms of action of adiponectin are directed to a protective role against atherogenic and insulin resistance processes. Research has revealed interesting new functions far beyond metabolism, such as immunity, cancer and bone formation. Contrary to all adipose-related proteins, adiponectin decreases with obesity. Most of the contradictory data surrounding adiponectin are related to plasma values and their relationship with body fat, gender differences and insulin resistance. There are important confounding results regarding the mechanisms of action and functions of adiponectin, especially in relation to insulin resistance and inflammation.

Expression of cortisol metabolism-related genes shows circadian rhythmic patterns in human adipose tissue

Objective:To analyze, in morbid obese patients, the expression of several human genes regulating cortisol metabolism, such as glucocorticoid receptor (GR), 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2), stearoyl-acute regulatory protein (StAR), 5α-reductase type I (5α-R) and peroxisome proliferator-activated receptor-γ (PPARγ) in two different adipose depots. A second objective was to characterize the circadian rhythmicity of these genes in both adipose tissue (AT) regions.Design:Visceral and subcutaneous abdominal AT biopsies were obtained from obese patients (body mass index ⩾40 kg m−2). To carry out rhythmic expression analysis, AT explants were cultured for 24 h and gene expression at times (T) 0, 6, 12 and 18 h, was performed with quantitative real-time PCR.Result:GR, 11βHSD1 and PPARγ genes were highly expressed in both subcutaneous and visceral depots. StAR and 5α-R genes were detected at lower levels. The expression of 11βHSD2 was quantified in both AT depots with a higher expression in the visceral depot (P=0.032). Both sexes had similar gene expression levels, except for 5α-R (P=0.002). The genes studied showed circadian rhythmicity being more robust in visceral than in subcutaneous AT. Genes ranged in anti-phase between both depots (P=0.002). This rhythmicity was maintained in an AT culture.Conclusion:We have shown for the first time circadian rhythmicity in glucocorticoid-related gene expression in human AT ex vivo. These results may have potential therapeutic implications with respect to the pathogenesis and treatment of diseases, such as obesity, type 2 diabetes and cardiovascular diseases.

Role of DHEA-S on body fat distribution: Gender- and depot-specific stimulation of adipose tissue lipolysis

The objective of this work was to study the possible impact of DHEA-S on body fat distribution and the specific action of the hormone on lipolysis from visceral and subcutaneous human adipose tissue. First, a clinical evaluation was performed in 84 obese patients (29 men, 55 women), measuring serum DHEA-S, computed tomography (CT) anthropometric parameters of abdominal fat distribution. In a second experiment, subcutaneous and visceral adipose tissue samples were obtained from 20 obese patients (10 men, 10 women) and cultured in vitro under stimulation with DHEA-S to further assess a possible effect of this hormone on adipose tissue lipolysis. Serum DHEA-S was inversely and specifically associated with visceral fat area (VA) as assessed by CT in men and with waist-to-hip ratio in women. In vitro, DHEA-S increased lipolysis in womens subcutaneous adipose tissue at 2 h, while in men, the effect was evident in visceral tissue and after 24 h of treatment. In conclusion, DHEA-S contributes to gender-related differences in body fat distribution probably by a differential lipolytic action. We have demonstrated for the first time in vitro that DHEA-S stimulates lipolysis preferably in subcutaneous fat in women and in visceral fat in men.

Relation between degree of obesity and site-specific adipose tissue fatty acid composition in a Mediterranean population

OBJECTIVE Obesity itself could be a key factor determining fatty acid (FA) composition of adipose tissue (AT). A Mediterranean diet influences this relationship. However, a relation between different overweight and obesity levels (including morbidly obese subjects) and AT FA pattern has not been fully established. The objective of the present study was to analyze potential differences in AT FA composition attending to degree of obesity in patients who follow a Mediterranean dietary pattern. METHODS Our study comprises 60 patients classified as overweight, obese, or morbidly obese (20 subjects in each group). Dietary composition was assessed by a 7-d record, and visceral and subcutaneous AT FAs were analyzed by gas chromatography. Cardiometabolic risk-related parameters were also assessed. RESULTS Our results showed that dietary habits were similar among groups, although palmitic intake was higher and palmitoleic intake was lower in the morbidly obese group. Concerning AT, we observed significant differences in the visceral depot. Concretely, both total monounsaturated FA (P = 0.039) and palmitoleic acid (P = 0.008) were higher in overweight subjects. Most differences were found in the subcutaneous tissue. Among them, n-9 and total monounsaturated FA (P < 0.001) were significantly higher again in overweight subjects, while 22:6n-3 was higher in morbidly obese subjects. Subcutaneous adipose dihommo-γ-linolenic content and dietary palmitic and palmitoleic acids were independent predictors of body mass index. CONCLUSIONS We confirm the relationship between degree of obesity and dietary and AT FA composition in this Mediterranean population. Despite a similar dietary pattern among groups, overweight and morbidly obese patients have a less detrimental FA profile than obese patients, probably due to differences in adipose tissue metabolism.

Two-dimensional predictive equation to classify visceral obesity in clinical practice

Objective: Visceral obesity assessment is not easy, and although computed tomography (CT) is an accurate tool, this technique is expensive and sometimes not suitable in clinical practice. We developed a new two‐dimensional elliptical anthropometric equation to classify visceral obesity and evaluated the validity and the reliability of the new equation compared with CT.

Insulin effect on adipose tissue (AT) adiponectin expression is regulated by the insulin resistance status of the patients.

Objective  The objective of the present study was to determine a possible depot‐specific effect of insulin‐stimulation on adiponectin gene expression in adipose tissue (AT) explants from subcutaneous and visceral AT. A secondary aim was to analyse the associations of adiponectin plasma levels, as well as control and insulin‐stimulated gene expression levels with different features of the metabolic syndrome.

Anthropometric indexes for visceral fat estimation in overweight/obese women attending to age and menopausal status

The objective of the present study was to assess the usefulness and accuracy of different anthropometric measurements in the diagnosis of abdominal visceral obesity in overweight/obese women attending to age and menopausal status. The secondary objective was to evaluate the usefulness of waist circumference (WC) in two different sites. Different anthropometric indicators were assessed in 55 overweight/obese women (n=22 premenopausal, n=33 postmenopausal; BMI > 25 kg/m2) and compared with computed tomography measurements of abdominal visceral adipose tissue (VA) performed as a single scan at L4–L5. Our results show that VA significantly differs between both groups of women. Waist2-hip ratio (W2HR) was significantly correlated to VA in both groups of women. After multiple regression analysis, sagittal diameter was an independent parameter to predict VA. However, no significant differences were obtained in this diameter between both groups. None of the waist circumferences were significantly associated to VA. Moreover, the two sites of WC were statistically different. In conclusion, waist-to-hip ratio, measured immediately above the iliac crest (W2HR) seems to be the more appropriated anthropometric index for the estimation of visceral fat in women, independently of age. Although sagittal diameter is a fine parameter to predict visceral fat area, it is not adequate to discriminate between women of different age or menopausal status. In contrast with previous findings, waist circumferences do not seem to be useful for predicting VA.ResumenEn el presente estudio se valora la utilidad y precisión de diferentes medidas antropométricas para diagnosticar la obesidad visceral en mujeres con sobrepeso/obesidad según la edad y el estatus menopáusico. También se evalúa la utilidad de la circunferencia de la cintura (C) medida en dos localizaciones diferentes. Para ello, se midieron diversos parámetros antropométricos en 55 mujeres con IMC>25 kg/m2 (n=22 premenopáusicas, n=33 postmenopáusicas) y se compararon estos datos con un escáner de tomografía computerizada del tejido adiposo visceral (AV) de la región abdominal. Según nuestros resultados, el AV resultó significativamente diferente entre ambos grupos de mujeres. El índice cintura-cadera2 (ICC2) se correlacionó con el AV. Tras un análisis de regresión múltiple, el parámetro independiente para predecir el AV fue el diámetro sagital, aunque no se encontraron diferencias significantivas en este diámetro en ambos grupos. Ninguna de las medidas de la cintura se correlacionó significativamente con el AV. Los dos perímetros de cintura fueron significativamente diferentes. En conclusión, aunque el diámetro sagital es un buen parámetro para predecir el AV, no es adecuado para discriminar diferencias en mujeres. El índice cintura-cadera2 (medido justo encima de la cresta ilíaca) parece ser el índice más apropiado para la estimación del AV, independientemente de la edad y estatus menopáusico. En contra de observaciones previas, el perímetro de cintura no es útil para predecir el AV en mujeres.