New adipokines vaspin and omentin. Circulating levels and gene expression in adipose tissue from morbidly obese women

<p>Abstract</p> <p>Background</p> <p>Vaspin and omentin are recently described molecules that belong to the adipokine family and seem to be related to metabolic risk factors. The objectives of this study were twofold: to evaluate vaspin and omentin circulating levels and mRNA expression in subcutaneous and visceral adipose tissues in non-diabetic morbidly obese women; and to assess the relationship of vaspin and omentin with anthropometric and metabolic parameters, and other adipo/cytokines.</p> <p>Design</p> <p>We analysed vaspin and omentin circulating levels in 71 women of European descent (40 morbidly obese [BMI ≥ 40 kg/m²] and 31 lean [BMI ≤ 25]). We assessed vaspin and omentin gene expression in paired samples of visceral and subcutaneous abdominal adipose tissue from 46 women: 40 morbidly obese and 6 lean. We determined serum vaspin and plasma omentin levels with an Enzyme-Linked Immunosorbent Assay and adipose tissue mRNA expression by real time RT-PCR.</p> <p>Results</p> <p>Serum vaspin levels in the morbidly obese were not significantly different from those in controls. They correlated inversely with levels of lipocalin 2 and interleukin 6. Vaspin mRNA expression was significantly higher in the morbidly obese, in both subcutaneous and visceral adipose tissue.</p> <p>Plasma omentin levels were significantly lower in the morbidly obese and they correlated inversely with glucidic metabolism parameters. Omentin circulating levels, then, correlated inversely with the metabolic syndrome (MS). Omentin expression in visceral adipose tissue was significantly lower in morbidly obese women than in controls.</p> <p>Conclusions</p> <p>The present study indicates that vaspin may have a compensatory role in the underlying inflammation of obesity. Decreased omentin circulating levels have a close association with MS in morbidly obese women.</p

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El carácter integrador de la legislación y de los instrumentos de gestión ambiental y la competencia exclusiva y excluyente de la Superintendencia del Medio Ambiente para la fiscalización, seguimiento y sanción de los instrumentos de gestión ambiental...

The General Environmental Act Nº 19.300, -that was deepen by the enactment of the Act Nº 20.417 that “creates the Ministry of the Environment; the Environmental Assessment Service; and the Environmental Superintendence” - establishes a regime that integrates environmental legislation with instruments of environmental management contained within the Law; due to the fact that diverse sectorial aspects are considered within its creation. The article argues that the most important achievement with the creation of the new environmental framework is to have located at the Environmental Superintendence both enforcement and sanctions of the environmental management instruments mentioned in Article 2nd of the Organic Law of the Environmental Superintendence; as a solution to the dispersion and overlap of the enforcement and sanctions powers; which were the causes of major damage and lack of juridical certainty to the regulated community; ensuring this way both normative and guiding coherence of the environmental enforcement activities in the country.La Ley N° 19.300, sobre Bases Generales del Medio Ambiente, modelo que se profundizó con la publicación de la Ley N° 20.417, que “Crea el Ministerio, el Servicio de Evaluación Ambiental y la Superintendencia del Medio Ambiente”, establece un régimen integrador de la legislación ambiental y de los instrumentos de gestión ambiental en ella contenidos, en cuanto consideran diversos aspectos sectoriales en su generación. El artículo concluye que el gran avance de la nueva institucionalidad ambiental es haber radicado en la Superintendencia del Medio Ambiente la fiscalización y sanción de los instrumentos de gestión ambiental señalados en el artículo 2° de la Ley Orgánica de la Superintendencia del Medio Ambiente, como solución a la dispersión y superposición de las potestades de fiscalización y sanción que ocasionan graves perjuicios y falta de certeza jurídica a los regulados; asegurando coherencia normativa y rectora de la fiscalización ambiental del país

El carácter integrador de la legislación y de los instrumentos de gestión ambiental y la competencia exclusiva y excluyente de la Superintendencia del Medio Ambiente para la fiscalización, seguimiento y sanción de los instrumentos de gestión ambiental...

La Ley N° 19.300, sobre Bases Generales del Medio Ambiente, modelo que se profundizó con la publicación de la Ley N° 20.417, que “Crea el Ministerio, el Servicio de Evaluación Ambiental y la Superintendencia del Medio Ambiente”, establece un régimen integrador de la legislación ambiental y de los instrumentos de gestión ambiental en ella contenidos, en cuanto consideran diversos aspectos sectoriales en su generación. El artículo concluye que el gran avance de la nueva institucionalidad ambiental es haber radicado en la Superintendencia del Medio Ambiente la fiscalización y sanción de los instrumentos de gestión ambiental señalados en el artículo 2° de la Ley Orgánica de la Superintendencia del Medio Ambiente, como solución a la dispersión y superposición de las potestades de fiscalización y sanción que ocasionan graves perjuicios y falta de certeza jurídica a los regulados; asegurando coherencia normativa y rectora de la fiscalización ambiental del país

Deregulated Serotonin Pathway in Women with Morbid Obesity and NAFLD

Non-alcoholic fatty liver disease (NAFLD) extends from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH). Peripheral serotonin (5-HT) has become as an important regulator of different metabolic pathways. 5-HT has been related to obesity and lipid accumulation in the liver. The objective of this study was to assess the relationship between the 5-HT signaling pathway and the degree of NAFLD, as well as to investigate whether peripheral 5-HT levels are related to the hepatic and jejunal mRNA abundance of serotonin receptors (HTR) in a cohort of women with morbid obesity (MO) and NAFLD. ELISA was used to quantify the serum 5-HT from normal-weight subjects (n = 26) and patients with MO (n = 58). We used RTq-PCR analysis to evaluate the relative expression of HTR in women with MO with normal liver (n = 22), SS (n = 21), and NASH (n = 15). The 5-HT was diminished in women with MO under a hypocaloric diet, regardless of the presence of NAFLD. Additionally, we report a negative correlation of 5-HT levels with metabolic syndrome criteria, suggesting that serotonin may have a protective role in obesity. Additionally, the hepatic expression of HTR2A and HTR2B were decreased in women with MO and NAFLD, but no significant differences in the HTR jejunal expression according to the presence of NAFLD were found

Circulating Levels of Pro-Neurotensin and Its Relationship with Nonalcoholic Steatohepatitis and Hepatic Lipid Metabolism

Recent studies suggest a link between pro-neurotensin (pro-NT) and nonalcoholic fatty liver disease (NAFLD), but the published data are conflicting. Thus, we aimed to analyze pro-NT levels in women with morbid obesity (MO) and NAFLD to investigate if this molecule is involved in NAFLD and liver lipid metabolism. Plasma levels of pro-NT were determined in 56 subjects with MO and 18 with normal weight (NW). All patients with MO were subclassified according to their liver histology into the normal liver (NL, n = 20) and NAFLD (n = 36) groups. The NAFLD group had 17 subjects with simple steatosis (SS) and 19 with nonalcoholic steatohepatitis (NASH). We used a chemiluminescence sandwich immunoassay to quantify pro-NT in plasma and RT-qPCR to evaluate the hepatic mRNA levels of several lipid metabolism-related genes. We reported that pro-NT levels were significantly higher in MO with NAFLD than in MO without NAFLD. Additionally, pro-NT levels were higher in NASH patients than in NL. The hepatic expression of lipid metabolism-related genes was found to be altered in NAFLD, as previously reported. Additionally, although pro-NT levels correlated with LDL, there was no association with the main lipid metabolism-related genes. These findings suggest that pro-NT could be related to NAFLD progression

Increased Hepatic <i>ATG7</i> mRNA and ATG7 Protein Expression in Nonalcoholic Steatohepatitis Associated with Obesity

The autophagy gene ATG7 has been shown to be essential for the induction of autophagy, a process that used to be suppressed in nonalcoholic fatty liver disease (NAFLD). However, the specific role of ATG7 in NAFLD remains unclear. The aim of this study was to analyze hepatic ATG7 mRNA and ATG7 protein expression regarding obesity-associated NAFLD. Patients included women classified into normal weight (NW, n = 6) and morbid obesity (MO, n = 72). The second group was subclassified into normal liver (NL, n = 11), simple steatosis (SS, n= 29), and nonalcoholic steatohepatitis (NASH, n = 32). mRNA expression was analyzed by RT–qPCR and protein expression was evaluated by Western blotting. Our results showed that NASH patients presented higher ATG7 mRNA and ATG7 protein levels. ATG7 mRNA expression was increased in NASH compared with SS, while ATG7 protein abundance was enhanced in NASH compared with NL. ATG7 mRNA correlated negatively with the expression of some hepatic lipid metabolism-related genes and positively with endocannabinoid receptors, adiponectin hepatic expression, and omentin levels. These results suggest that ATG7-mediated autophagy may play an important role in the pathogenesis of NAFLD, especially in NASH, perhaps playing a possible protective role. However, this is a preliminary study that needs to be further studied

Deregulation of Secreted Frizzled-Related Protein 5 in Nonalcoholic Fatty Liver Disease Associated with Obesity

Secreted frizzled-related protein 5 (SFRP5), an antagonist of the noncanonical WNT pathway, has a controversial role in liver disease. The aim of this study was to analyze the role of SFRP5 and the noncanonical WNT pathway in nonalcoholic fatty liver disease (NAFLD). Plasma SFRP5 levels were determined by ELISA in women with normal weight (NW; n = 20) and morbid obesity (MO; n = 69). Women with MO were subclassified according to hepatic histology into normal liver (NL; n = 28), NAFLD (n = 41) (simple steatosis (SS; n = 24), and nonalcoholic steatohepatitis (NASH; n = 17)). We used RT-qPCR to evaluate the hepatic mRNA expression of SFRP5, WNT5A, and JNK in women with MO. SFRP5 levels were lower in NW than in MO patients who underwent a very low-calorie diet before surgery. Hepatic SFRP5 mRNA expression was higher in SS than in NL or NASH; additionally, patients with hepatic inflammation or ballooning presented lower SFRP5 abundance. WNT5A and JNK expression was enhanced in NAFLD compared with NL. In conclusion, circulating SFRP5 levels depend on the diet, and hepatic SFRP5 seems to have a protective role in the first steps of NAFLD; however, SFRP5 could be deregulated in an advanced stage while WNT5A and JNK are activated, promoting liver damage

Increased Secreted Frizzled-Related Protein 5 mRNA Expression in the Adipose Tissue of Women with Nonalcoholic Fatty Liver Disease Associated with Obesity

Secreted frizzled-related protein 5 (SFRP5) is an anti-inflammatory adipocytokine secreted by adipocytes that seems to be linked with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the role of the SFRP5-wingless-MMTV integration site family member 5a (WNT5A) pathway, closely related to adipogenesis, in subcutaneous (SAT) and visceral adipose tissues (VAT) and its relationship with obesity-related NAFLD. Our cohort was composed of 60 women with morbid obesity (MO), who underwent hypocaloric diet, subclassified according to their hepatic histopathology and 15 women with normal weight. We observed increased SFRP5 mRNA expression in VAT and lower WNT5A expression in SAT in MO compared to normal weight. We found elevated SFRP5 expression in nonalcoholic steatohepatitis (NASH) in SAT and in mild simple steatosis (SS) and NASH in VAT. We observed higher WNT5A expression in SS compared to normal liver in SAT, and a peak of WNT5A expression in mild SS. To conclude, we reported increased SFRP5 mRNA expression in SAT and VAT of NAFLD-related to obesity subjects, suggesting an implication of the SFRP5-WNT5A pathway in NAFLD pathogenesis, probably due to the adipose tissue-liver axis. Since the mechanisms by which this potential interaction takes place remain elusive, more research in this field is needed