Silencing of matrix metalloprotease-12 delays the progression of castration-resistant prostate cancer by regulating autophagy and lipolysis

Abstract The complex pathogenesis of castration-resistant prostate cancer (CRPC) makes it challenging to identify effective treatment methods. Matrix metalloproteinase (MMP)-12 can degrade elastin as well as various extracellular matrix (ECM) components, which is associated with cancer progression. However, the relationship between MMP-12 and CRPC progression is poorly understood. In this study, we observed the effect of MMP-12 on the progression of CRPC and further explored its potential mechanism of action. High levels of MMP-12 were observed in patients with CRPC. We therefore developed cell co-culture and mouse models to study the function of MMP-12. Silencing MMP-12 in CRPC cells disrupted lipid utilization and autophagy marker expression via the CD36/CPT1 and P62/LC3 pathways, respectively, leading to reduced CRPC cell migration and invasion. Moreover, animal experiments confirmed that MMP-12-knockdown CRPC xenograft tumors exhibited reduced tumor growth, and the mechanisms involved the promotion of cancer cell autophagy and the inhibition of lipid catabolism. According to our results, MMP-12 played important roles in the progression of CRPC by disrupting adipocyte maturation and regulating cancer migration and invasion via the modulation of autophagy and lipid catabolism pathways.

Qualidade das informações sobre lipoaspiração para o público leigo: Uma revisão de escopo / Quality of information about liposuction for the lay public: A scoping review

Introdução: Esta revisão de escopo tem por objetivo analisar a qualidade das informações sobre lipoaspiração para o público leigo. Método: Foi realizada busca na literatura no período de 18 de novembro a 12 de dezembro de 2021 nas seguintes plataformas de base de dados: Medline, Cochrane, LILACS, Embase e BVS. A estratégia de busca envolveu a combinação de vários descritores. Três investigadores independentes leram o resumo dos estudos que foram obtidos usando a estratégia de busca para avaliar aqueles que preenchiam os critérios de elegibilidade. Resultados: Inicialmente, foram levantados 33 artigos utilizando a estratégia de busca. Dentre esses, 23 estudos foram excluídos após a leitura dos resumos e avaliação dos critérios de elegibilidade, por não possuírem desfechos de interesse ao tema proposto. Assim, dez estudos preenchiam os critérios de inclusão, sendo nove estudos transversais e uma revisão de literatura. Dentre os dez artigos incluídos, nove relatam que as informações sobre lipoaspiração são precárias e imprecisas. Conclusão: O conteúdo sobre lipoaspiração disponibilizado ao público leigo por meio da Internet é, na sua maioria, insatisfatório.

Introduction: This scoping review aims to analyze the quality of information about liposuction for the lay public. Method: A literature search was carried out from November 18 to December 12, 2021, on the following database platforms: Medline, Cochrane, LILACS, Embase, and VHL. The search strategy involved the combination of several descriptors. Three independent investigators read the abstract of studies obtained using the search strategy to evaluate those that met the eligibility criteria. Results: Initially, 33 articles were collected using the search strategy. Among these, 23 studies were excluded after reading the abstracts and evaluating the eligibility criteria, as they did not have outcomes of interest to the proposed topic. Thus, ten studies met the inclusion criteria, nine of which were cross-sectional and one literature review. Among the ten articles included, nine report that information about liposuction is poor and inaccurate. Conclusion: The content on liposuction made available to the lay public via the Internet is, for the most part, unsatisfactory.

Efficacy, safety, and potential industry bias in using deoxycholic acid for submental fat reduction - A systematic review and meta-analysis of randomized clinical trials

Abstract Lipolytic substance injections to reduce localized fat have been extensively used because it is a low-invasive method. This review aimed to evaluate the efficacy and safety of deoxycholic acid in submental fat reduction compared to a placebo and investigate the potential industry sponsorship bias in the results of randomized clinical trials on this topic. Ten electronic databases were extensively searched for randomized clinical trials without restriction on language and year of publication. Two reviewers extracted the data and assessed the individual risk of bias in the studies with the RoB 2.0 tool. The industry sponsorship bias was evaluated according to citations in the articles regarding industry funding/sponsorship throughout the texts. Fixed and random effects meta-analyses were performed, and the results were reported in Risk Ratio (RR) at a 95% Confidence Interval (95% CI). The initial search provided 5756 results, of which only five were included. Only two studies had a low risk of bias. All studies showed a potential industry bias. The meta-analysis showed that patients treated with deoxycholic acid had significant positive results for all efficacy outcomes and a higher risk of fibrosis, pain, erythema, numbness, swelling, edema, pruritus, nodules, headache, and paresthesia. The low to moderate certainty of evidence found allows concluding that deoxycholic acid is effective in submental fat reduction, causing well-tolerated adverse effects. However, all eligible studies showed a potential industry bias.

Hipertrofia y resistencia a la insulina en un modelo in vitro de obesidad y DMT2 inducida por alta glucosa e insulina / Hypertrophy and insulin resistance in an in vitro model of obesity and T2DM induced by high glucose and insulin

Resumen Introducción: La obesidad es considerada un factor de riesgo para desarrollar resistencia a la insulina. La expansión del tejido adiposo se ha relacionado con el aumento de la producción de citoquinas proinflamatorias que, junto a los ácidos grasos son responsables, al menos en parte, del desarrollo de la resistencia a la insulina y esta a su vez, facilita el desarrollo de diabetes mellitus tipo 2 (DMT2). Objetivo: El propósito de este estudio fue realizar y caracterizar un modelo in vitro de obesidad empleando concentraciones altas de glucosa e insulina en una línea de células adipocitarias. Métodos: Se indujo modelo de hipertrofia celular realizando un estímulo en adipocitos maduros con una concentración de glucosa (450 mg/dL) e insulina (106 pmol/L) (modelo HGHI). Tras estímulo se realizaron ensayos de viabilidad celular, diámetro celular, movilización de lípidos y marcadores de señalización de insulina. Resultados: Tras el tratamiento con HGHI, se evidencia hipertrofia adipocitaria, incremento en la acumulación de lípidos, reducción de la ruptura de éstos, alteración de la señalización de insulina y tendencia a modificación de proteínas de marcadores de estrés de retículo y estrés oxidativo. Conclusión: Estos resultados demuestran la validez del modelo in vitro que simula al menos en parte la obesidad asociada a insulino resistencia, siendo una herramienta útil para estudiar los mecanismos de susceptibilidad a obesidad y resistencia a la insulina inducida in vitro con diferentes moléculas.

Abstract Introduction: Obesity is considered a risk factor for developing insulin resistance. The increase in adipose tissue has been related to the increase in the production of pro-inflammatory cytokines, which together with fatty acids are responsible, at least in part, for the development of insulin resistance, and this in turn facilitates the development of T2 diabetes mellitus type 2 (DMT2). Objective: The purpose of this study was to perform and characterize an in vitro model of obesity using high concentrations of glucose and insulin on an adipocyte cell line. Methods: A cell hypertrophy model was induced by stimulating mature adipocytes with a concentration of glucose (450 mg/dL) and insulin (106 pmol/L) (HGHI model). The cell viability, cell diameter, lipid mobilization and insulin signalling markers were evaluated. Results: After HGHI treatment, adipocytes show hypertrophy, increase in lipid accumulation, reduction of lipid breakdown, alteration of insulin signalling, a tendency to modify proteins of reticulum stress markers and, oxidative stress. Conclusion: These results demonstrate a new in vitro model that simulates, at least in part, obesity associated with insulin resistance being a useful tool to study the mechanisms of susceptibility to obesity and insulin resistance induced in vitro by different molecules.

Effective fraction from Simiao Wan prevents hepatic insulin resistant by inhibition of lipolysis via AMPK activation / 中国天然药物

Simiao Wan (SMW) is a traditional Chinese formula, including Atractylodis Rhizoma, Achyranthis Bidentatae Radix, Phellodendri Chinensis Cortex and Coicis Semen at the ratio of 1:1:2:2. It can be used to the treatment of diabetes. However, its bioactive compounds and underlying mechanism are unclear. This study aimed to screen the antilipolytic fraction from SMW and investigate its therapeutic mechanisms on hepatic insulin resistance. Different fractions of SMW were prepared by membrane separation combined with macroporous resin and their antilipolytic activities were screened in fasted mice. The effects of 60% ethanol elution (ESMW) on lipolysis were investigated in 3T3-L1 adipocytes stimulated by palmitic acid (PA) and high fat diet (HFD)-fed mice. In our study, ESMW is the bioactive fraction responsible for the antilipolytic activity of SMW and 13 compounds were characterized from ESMW by UHPLC-QTOF-MS/MS. ESMW suppressed protein kinase A (PKA)-hormone-sensitive lipase (HSL) related lipolysis and increased AMP-activated protein kinase (AMPK) phosphorylation in PA challenged 3T3-L1 adipocytes. AMPKα knockdown abolished the inhibitory effects of ESMW on IL-6 and HSL pSer-660, revealing that the antilipolytic and anti-inflammatory activities of ESMW are AMPK dependent. Furthermore, ESMW ameliorated insulin resistance and suppressed lipolysis in HFD-fed mice. It inhibited diacylglycerol accumulation in the liver and inhibited hepatic gluconeogenesis. Conditional medium collected from ESMW-treated 3T3-L1 cells ameliorated insulin action on hepatic gluconeogenesis in liver cells, demonstrating the antilipolytic activity contributed to ESMW beneficial effects on hepatic glucose production. In conclusion, ESMW, as the antilipolytic fraction of SMW, inhibited PKA-HSL related lipolysis by activating AMPK, thus inhibiting diacylglycerol (DAG) accumulation in the liver and thereby improving insulin resistance and hepatic gluconeogenesis.

Effects of oleic (18: 1n-9) and palmitic (16: 0) fatty acids on the metabolic state of adipocytes / Efectos de los ácidos grasos oleico (18: 1n-9) y palmítico (16: 0) en el estado metabólico del adipocito

Abstract Background: Elevated serum-free fatty acid (FFA) levels induce insulin resistance (IR) or a protective mechanism to IR development in humans; it depends on FFA type. Objetive: This study explores the effects of oleic (OLA - unsatured) and palmitic (PAM - saturated) fatty acids on insulin action in mature adipocytes effect. Methods: Cells were incubated 18 h with or without OLA and PAM at 250 μM, and 500 μM. After the culture period, were measured: adipocyte viability, size, fatty acids mobilisation, insulin signalling proteins, and glucose uptake. Results: Adipocytes exhibited optimal viability tolerances regardless of the kinds of fatty acids used for treatment. However, adipocytes were hypertrophic after OLA and PAM stimuli. Additionally, lipogenesis (lipid synthesis), and lipolysis (lipid breakdown) were significantly increased by treatment with OLA, or PAM (500 μM) compared to control. Moreover, OLA results showed that there was no significant reduction in signalling cascades, except for a downstream proinflammatory response. Instead, PAM hypertrophic adipocytes were insulin resistant with alteration of proinflammatory and stress markers. Conclusions: Current findings suggest that PAM induces insulin resistance, mitochondrial and reticulum stress on fat cells compared to those treated with OLA that, protects adipocytes to all those alterations.

Resumen Introducción: Los niveles elevados de ácidos grasos libres (AGL) en suero inducen resistencia a insulina (RI) o un mecanismo de protección del desarrollo de RI en humanos, esto depende del tipo de AGL. Objetivo: Este estudio explora los efectos de los ácidos grasos oleico (insaturados - OLA) y palmítico (saturados - PAM) sobre la insulina en adipocitos maduros. Métodos: Las células se incubaron 18 h con o sin OLA y PAM a 250 μM y 500 μM. Después del período de cultivo, se evaluó en adipocitos: viabilidad, tamaño, movilización de ácidos grasos, proteínas de señalización de insulina y absorción de glucosa. Resultados: Los adipocitos mostraron viabilidad óptima independientemente de los tipos de ácidos grasos utilizados en el tratamiento. Los adipocitos eran hipertróficos tras estimulo con OLA y PAM. La lipogénesis (síntesis de lípidos) y la lipólisis (degradación de lípidos) aumentaron significativamente con el tratamiento con OLA o PAM (500 μM) en comparación con el control. En los resultados de OLA no se evidenció una reducción significativa en las cascadas de señalización de insulina, a excepción de una respuesta proinflamatoria posterior. En cambio, los adipocitos hipertróficos tratados con PAM presentaron resistencia a la insulina y alteración de los marcadores proinflamatorios y de estrés. Conclusiones: Nuestros hallazgos sugieren que PAM induce resistencia a la insulina, estrés mitocondrial y del retículo en las células grasas en comparación con aquellos tratados con OLA, AGL que, en cambio, protegen a los adipocitos de todas esas alteraciones.

Mechanistic studies of PEG-asparaginase-induced liver injury and hepatic steatosis in mice

PEGylated-l-asparaginase (PEG-ASNase) is a chemotherapeutic agent used to treat pediatric acute lymphoblastic leukemia (ALL). Its use is avoided in adults due to its high risk of liver injury including hepatic steatosis, with obesity and older age considered risk factors of the injury. Our study aims to elucidate the mechanism of PEG-ASNase-induced liver injury. Mice received 1500 U/kg of PEG-ASNase and were sacrificed 1, 3, 5, and 7 days after drug administration. Liver triglycerides were quantified, and plasma bilirubin, ALT, AST, and non-esterified fatty acids (NEFA) were measured. The mRNA and protein levels of genes involved in hepatic fatty acid synthesis,

In vitro lipolysis process and lipolysis mechanism of testosterone undecanoate type Ⅲ lipid formulations / 药学学报

The study evaluates the lipolysis rate and extent of type Ⅲ lipid formulations using testosterone undecanoate as a model drug after digestion with in vitro lipolysis model, and studies the digestive regularity with optical microscope and electrical conductivity. The results showed that for testosterone undecanoate type Ⅲ lipid formulations with castor oil as oil phase and Transcutol HP as latent solvent, the lipolysis rate and extent were increased with the increase of oil phase proportion and were decreased with excessive proportion of surfactant, in which can see liquid crystal phase during lipolysis process. The lipolysis rate of type ⅢB lipid preparations with different surfactant were ordered as Labrasol > Tween 80 > Cremophor EL, but the rate of type ⅢA is different in quick digestion phase and slow digestion phase. The lipolysis extent of type Ⅲ lipid formulations with different surfactant were ordered as Cremophor EL > Tween 80 > Labrasol. These may be related to the digestive effect of pancreatic lipase on different surfactants. This study implied that the lipolysis rate and extent of type Ⅲ lipid formulations are greatly influenced by the proportion of oil phase and surfactant, and the surfactant structure. These factors will affect the in vivo digestion and should be taken into account when screening type Ⅲ lipid formulations.

Gastrointestinal lipolysis and trans-epithelial transport of SMEDDS

Self-microemulsifying drug delivery systems (SMEDDSs) have recently returned to the limelight of academia and industry due to their enormous potential in oral delivery of biomacromolecules. However, information on gastrointestinal lipolysis and trans-epithelial transport of SMEDDS is rare. Aggregation-caused quenching (ACQ) fluorescent probes are utilized to visualize the

Pseudomonas spp. and other psychrotrophic microorganisms in inspected and non-inspected Brazilian Minas Frescal cheese: proteolytic, lipolytic and AprX production potential / Pseudomonas spp. e outros micro-organismos psicrotróficos em queijos Minas Frescal inspecionados e não inspecionados: potencial proteolítico, lipolítico e produção de AprX

The most consumed cheese in Brazil, Minas Frescal cheese (MFC) is highly susceptible to microbial contamination and clandestine production and commercialization can pose a risk to consumer health. The storage of this fresh product under refrigeration, although more appropriate, may favor the growth of spoilage psychrotrophic bacteria. The objective of this study was to quantify and compare Pseudomonas spp. and other psychrotrophic bacteria in inspected and non-inspected MFC samples, evaluate their lipolytic and proteolytic activities and their metalloprotease production potentials. Twenty MFC samples were evaluated: 10 inspected and 10 non-inspected. Counts of psychrotrophic bacteria and Pseudomonas spp., evaluation of the proteolytic and lipolytic potential of the isolates, and identification of potential producers of alkaline metalloprotease (AprX) were assessed. The mean total psychrotrophic counts were 1.07 (±2.18) × 109CFU/g in the inspected samples and 4.5 (±5.86) × 108CFU/g in the non-inspected, with no significant difference (p=0.37). The average score of Pseudomonas spp. was 6.86 (±18.6) × 105 and 2.08 (±3.65) × 106 CFU/g for the inspected and non-inspected MFC samples, respectively, with no significant difference (p=0.1). Pseudomonas spp. represented 0.06% and 0.004% of psychrotrophic bacteria found in inspected and non-inspected MFC samples, respectively. Collectively, 694 psychrotrophic strains and 47Pseudomonas spp. were isolated, of which 59.9% and 68.1% were simultaneously proteolytic and lipolytic, respectively. Of the 470 psychrotrophs isolated from inspected and 224 from non-inspected cheese samples, 5.74% and 2.23% contained aprX, respectively, while 100 and 86.96% of the Pseudomonas spp. isolates in inspected and non-inspected cheese samples contained the gene. The production potential of AprX did not, however, determine the proteolytic activity on plates of these isolates under the conditions evaluated in this study. Of total, 65.63% of the psychrotrophs that contained aprX gene were confirmed as Pseudomonas spp., using genus-specific PCR. Phylogenetic analysis of the 16S rRNA gene of the other psychrotrophs that were potential producers of AprX identified them as Serratia spp. (n=7), Raoultella ornithinolytica (n=1), and Acinetobacter schindleri (n=1) in the inspected samples and Psychrobacter sanguinis (n=1) and Leuconostoc mesenteroides (n=1) in the non-inspected samples. The production conditions of Brazilian MFC of these samples, while meeting the legal determinations, are not sufficient to control Pseudomonas and other spoilage-related psychrotrophs. Thus, stricter hygienic measures are required during the formal production of this type of cheese.(AU)

O mais consumido no Brasil, o queijo Minas Frescal (QMF) é altamente suscetível à contaminação microbiana e a produção e comercialização clandestina podem representar um risco para a saúde do consumidor. O armazenamento deste produto fresco sob refrigeração, embora mais apropriado, pode favorecer a multiplicação de bactérias psicrotróficas deteriorantes. O objetivo deste estudo foi quantificar e comparar Pseudomonas spp. e outras bactérias psicrotróficas em amostras de QMF inspecionadas e não inspecionadas, avaliar o potencial lipolítico, proteolítico e de produção de metaloprotease alcalina. Vinte amostras de QMF foram avaliadas: 10 inspecionadas e 10 não inspecionadas. Foram avaliadas as contagens de bactérias psicrotróficas e Pseudomonas spp., o potencial proteolítico e lipolítico dos isolados e a identificação de potenciais produtores de metaloprotease alcalina (AprX). A média total das contagens de bactérias psicrotróficas foi de 1,07 (±2,18) × 109UFC/g nas amostras inspecionadas e 4,5 (±5,86) × 108UFC/g nas não inspecionadas, sem diferença significativa (p=0,37). A média de Pseudomonasspp. foi de 6,86 (±18,6) × 105 e 2,08 (±3,65) × 106UFC/g para as amostras QMF inspecionadas e não-inspecionadas, respectivamente, sem diferença significativa (p=0,1). Pseudomonas spp. representaram 0,06% e 0,004% de bactérias psicrotróficas encontradas em amostras QMF inspecionadas e não-inspecionadas, respectivamente. Das amostras inspecionadas e não inspecionadas, foram isoladas 694 colônias psicrotróficas e 47 Pseudomonasspp., dos quais 59,9% e 68,1% foram simultaneamente proteolíticos e lipolíticos, respectivamente. Dos 470 isolados de psicrotróficos das amostras de queijo inspecionados e dos 224 isolados das não inspecionadas, 5,74% e 2,23% continham o gene aprX, respectivamente, enquanto 100 e 86,96% das Pseudomonasspp. isoladas em amostras de queijo inspecionadas e não inspecionadas continham o potencial de expressão de AprX. Esse potencial, no entanto, não determinou a atividade proteolítica em placas desses isolados nas condições avaliadas neste estudo. Do total, 65,63% dos psicrotróficos que continham o gene aprX foram confirmados como Pseudomonasspp., utilizando PCR gênero-específico. A análise filogenética do gene 16S rRNA dos outros psicrotróficos que foram produtores potenciais de AprX os identificou como Serratia spp. (n=7), Raoultella ornithinolytica (n=1) e Acinetobacter schindleri (n=1) nas amostras inspecionadas e Psychrobacter sanguinis (n=1) e Leuconostoc mesenteroides (n=1) nas amostras não inspecionadas. As condições de produção do QMF dessas amostras, atendendo às determinações legais, não são suficientes para controlar a Pseudomonas e outros psicrotróficos relacionados à deterioração. Assim, medidas higiênicas mais rígidas são necessárias durante a produção formal deste tipo de queijo.(AU)

Maximal fat oxidation during aerobic exercise in adolescents with type 1 diabetes / Oxidação máxima de gorduras durante o exercício aeróbico em adolescentes com diabetes tipo 1 / Oxidación máxima de grasas durante el ejercicio aeróbico en adolescentes con diabetes tipo 1

ABSTRACT Objective: To compare maximal fat oxidation rates (FATMAX) and analyze their association with cardiorespiratory fitness in adolescents with type 1 diabetes mellitus (T1DM). Methods: Twenty-two male and female adolescents aged between 11 to 17 years, following clinical and anthropometric evaluations, were assigned to the diabetic group (DG; n = 10) or control group (CG; n = 12). Cardiorespiratory fitness was determined by maximal oxygen uptake (VO2max) during a maximal aerobic test on a cycle ergometer using the Balke protocol. Maximal fat oxidation (FATMAX) was determined by the respiratory exchange ratio proposed in the Lusk table. Results: Adolescents in the DG had lower mean FATMAX (p<0.01) and %VO2FATMAX (p=0.001) values when compared with those in the CG. FATMAX values were inversely correlated with serum glycosylated hemoglobin (HbA1c) levels (r= −0.77) and directly correlated with BMI z-scores (r=0.76), while %VO2FATMAX results were correlated with age (r=0.81), BMI z-scores (r=0.65), and VO2max values (r=0.81). On multiple linear regression, HbA1c values explained 54% (adjusted r²=0.54, p=0.009) and BMI z-scores explained 3.1% (adjusted r²=-0.031, p=0.009) of the variation in FATMAX in the DG. Adolescents with T1DM had similar cardiorespiratory fitness and lower FATMAX rates (35±11 VO2max) when compared with controls (60±12 VO2max). Conclusion: These results suggest lower fat oxidation rates and greater use of glucose as an energy substrate during exercise and worse control in T1DM. Therefore, results may contribute to appropriate exercise prescription in T1DM, after verifying exercise intensity to reduce hypoglycemia risk. Level of evidence III; Case-control study.

RESUMO Objetivo: Comparar as taxas máximas de oxidação da gordura (FATMAX) e analisar a sua associação com a aptidão cardiorrespiratória em adolescentes com diabetes mellitus tipo 1 (DM1). Métodos: Vinte e dois adolescentes de ambos os sexos, de 11 a 17 anos, após avaliações clínicas e antropométricas, foram alocados no grupo diabético (GD; n = 10) ou no grupo controle (GC; n = 12). A aptidão cardiorrespiratória foi determinada pelo consumo máximo de oxigênio (VO2max) durante um teste aeróbico máximo em um cicloergômetro utilizando o protocolo Balke. A oxidação máxima da gordura (FATMAX) foi determinada pela razão de troca ventilatória proposta na Tabela de Lusk. Resultados: Os adolescentes no GD apresentaram menores valores médios de FATMAX (p<0,01) e % VO2FATMAX (p=0,001) quando comparados com aqueles no GC. Os valores de FATMAX correlacionaram-se inversamente com os níveis de hemoglobina glicosilada sérica (HbA1c) (r = −0,77) e diretamente com o z-score IMC (r = 0,76), enquanto os resultados de %VO2FATMAX correlacionaram-se diretamente com a idade (r = 0,81), z-score IMC (r = 0,65) e VO2max (r = 0,81). Na regressão linear múltipla, os valores de HbA1c explicaram 54% (r² ajustado = 0,54, p = 0,009) e o z-score IMC explicou 3,1% (r² ajustado = −0,031, p = 0,009) da variação no FATMAX no GD. Os adolescentes com DM1 apresentaram aptidão cardiorespiratória similar e taxas de FATMAX menores (35±11 VO2max) quando comparados com os do grupo controle (60±12 VO2max). Conclusão: Esses resultados sugerem taxas menores de oxidação da gordura e maior uso da glicose como substrato de energia durante o exercício e pior controle no DM1. Portanto, os resultados podem contribuir com a prescrição de exercício apropriada no DM1, após verificar a intensidade do exercício, a fim de diminuir o risco de hipoglicemia. Nível de evidência III; Estudo de caso-controle.

RESUMEN Objetivo: Comparar las tasas máximas de oxidación de la grasa (FATMAX) y analizar su asociación con la aptitud cardiorrespiratoria en adolescentes con diabetes mellitus tipo 1 (DM1). Métodos: Veintidós adolescentes de ambos sexos, de 11 a 17 años, después de evaluaciones clínicas y antropométricas, fueron asignados en el grupo diabético (GD, n = 10) o en el grupo control (GC, n = 12). La aptitud cardiorrespiratoria fue determinada por el consumo máximo de oxígeno (VO2max) durante un test aeróbico máximo en un cicloergómetro utilizando el protocolo Balke. La oxidación máxima de la grasa (FATMAX) fue determinada por la razón de cambio ventilatorio propuesta en la Tabla de Lusk. Resultados: Los adolescentes en el GD presentaron menores valores promedio de FATMAX (p<0,01) y % VO2FATMAX (p=0,001) cuando comparados con aquellos en el GC. Los valores de FATMAX se correlacionaron inversamente con los niveles de hemoglobina glicosilada sérica (HbA1c) (r = −0,77) y directamente con el z-score IMC (r = 0,76), mientras que los resultados de %VO2FATMAX se correlacionaron directamente con la edad (r = 0,81), z-score IMC (r = 0,65) y VO2max (r = 0,81). En la regresión lineal múltiple, los valores de HbA1c explicaron 54% (r² ajustado = 0,54, p = 0,009) y el z-score IMC explicó 3,1% (r² ajustado = −0,031, p = 0,009) de la variación en el FATMAX en el GD. Los adolescentes con DM1 presentaron aptitud cardiorrespiratoria similar y tasas de FATMAX menores (35±11 VO2max) cuando comparados con los del grupo control (60±12 VO2max). Conclusión: Esos resultados sugieren tasas menores de oxidación de la grasa y mayor uso de la glucosa como substrato de energía durante el ejercicio y peor control en la DM1. Por lo tanto, los resultados pueden contribuir con la prescripción de ejercicio apropiada en la DM1, después de verificar la intensidad del ejercicio, a fin de disminuir el riesgo de hipoglucemia. Nivel de evidencia III; Estudio de caso-control.

Molecular Basis of Pathogenesis of Ectopic Fat Deposition in DM2 – An Overview

The presence of fat, beyond physiological limits, in organs, other than the adipose tissue, like the liver, the skeletal muscle, the heart and the pancreas etc is called ectopic fat. It causes specific organ dysfunction in the tissues concerned. The importance of the ectopic fat is that it is connected to peripheral tissue insulin resistance, obesity, metabolic syndrome etc. Though the molecular mechanisms underlying the specific organ dysfunctions are understood, still grey areas exists as to the source ofthe ectopic fat and how it finds it’s way to the specific sites of the target organs (intra-myocellular in skeletal muscle, hepatocyte cytoplasm of liver,epicardial surface andcoronary arteries of heart etc.).The molecular mechanisms involving the actualectopic deposition fat, are not clear. This article focuses on some of the grey areas in the pathogenesis of the ectopic fat deposition, besides reviewing brieflythe factsalready known in the literature about ectopic fat deposition.

Non-surgical lipolysis techniques / 中华皮肤科杂志

In recent decades,non-invasive techniques have markedly developed.Non-invasive body contouring represents the fastest growing area of modem aesthetic medicine.Patients' fear of surgery has made micro-invasive and non-invasive lipolysis technology a hot topic in recent years.There are currently five leading non-invasive or micro-invasive techniques for reducing localized subcutaneous adipose tissue,including deoxycholic acid injection,cryolipolysis,ultrasonic lipolysis,radiofrequency lipolysis and laser lipolysis.This review mainly summarizes the recent findings regarding the action mechanisms,clinical efficacy of and adverse reactions to non-invasive lipolysis techniques.

Exploring the utility of the Chasing Principle: influence of drug-free SNEDDS composition on solubilization of carvedilol, cinnarizine and R3040 in aqueous suspension

This study assessed the influence of the composition of drug-free SNEDDS co-dosed with aqueous suspensions of carvedilol (CAR), cinnarizine (CIN) or R3040 on drug solubilization in a two-compartment lipolysis model. Correlation of drug log or solubility in SNEDDS with drug solubilization during lipolysis in the presence of drug-free SNEDDS was assessed. SNEDDS with varying ratios of soybean oil:Maisine 35-1 (1:1, /) and Kolliphor RH40, with ethanol at 10% (/) were used. SNEDDS were named F65, F55 and F20 (numbers refer to the percentage of lipids) and aqueous suspensions without drug-free SNEDDS (F0) were also analyzed. While the ranking order of drug solubilization was F65=F55=F20>F0 for CAR; F65=F55>F20>F0 for CIN and F65=F55=F20>F0 for R3040 - with higher CAR solubilization than for R3040 and CIN - the ranking of of CAR, CIN and R3040 in SNEDDS was F65F20 and F65>F55>F20, respectively. Therefore, the composition of SNEDDS influenced the solubilization of CIN, but not CAR and R3040. Furthermore, high in SNEDDS did not reflect high drug solubilization. As CAR (log 3.8) showed higher solubilization than CIN (log 5.8) and R3040 (log 10.4), a correlation between drug log and drug solubilization was observed.

Application of radiofrequency lipolysis combined with linear lifting in 237 cases of facial rejuvenation / 中华医学美学美容杂志

Objective To explore the application of radiofrequency lipolysis combined with line-ar lifting in fine lipolysis ,facial rejuvenation and treatment of common complications .Methods From February 2016 to October 2018 ,237 patients were treated by radiofrequency lipolysis combined with linear lifting .According to the patient's face shape ,skin laxity and fat accumulation ,the thickness of fat was measured by B-mode ultrasonography before operation ,and the operative plan was formulated after sufficient communication with the patients .Then ,we marked the range of lipolysis ,the orienta-tion of serrated line and the position of puncture point ,followed by the adjustment of the treatment parameters .Subsequently ,we placed FaceTite handle after swelling anesthesia ,moving slowly and fixing the treatment point ,as well as monitoring the temperature and swelling status of the skin .Im-mediately after the completion of lipolysis ,the treatment area of skin was ice compressed ,with the trocar needles inserted and serrated lines introduced for linear lifting operation .Neck-jaw sleeves were put on after operation .Results 237 patients had different degrees of post-operative edema ,of which the period ranged from 2 to 7 days .168 patients were followed up for 6 to 24 months ,and 8 patients had subcutaneous sclerosis that then gradually disappeared within 2 months after operation .Folliculitis occurred in 5 cases of scalp puncture ,and recovered after topical antibiotics .Facial skin relaxation and sagging ,fat accumulation ,facial shape ,pouch and wrinkles of 160 patients were improved in varying degrees ,and the outcomes of facial rejuvenation were obvious .However ,the self-reported treatment outcomes of 7 patients were not obvious .One patient was reported that the sagging of the skin after sacrificial lipolysis was worse than before ;48 patients underwent autologous fat transplantation ,botu-linum toxin injection ,hot pull ,E-light ,and water-light injection during the follow-up period ,and were not included in the evaluation of efficacy ;21 patients were lost to follow-up .Conclusions Radio-frequency lipolysis combined with linear lifting is an effective method for facial rejuvenation ,and it has obvious effect in fining lipolysis and facial rejuvenation by avoiding the disadvantage of single approach . Post-operative edema should be controlled and avoided to improve patients'satisfaction .

Fumigaclavine C attenuates adipogenesis in 3T3-L1 adipocytes and ameliorates lipid accumulation in high-fat diet-induced obese mice

Fumigaclavine C (FC), an active indole alkaloid, is obtained from endophytic Aspergillus terreus (strain No. FC118) by the root of Rhizophora stylosa (Rhizophoraceae). This study is designed to evaluate whether FC has anti-adipogenic effects in 3T3-L1 adipocytes and whether it ameliorates lipid accumulation in high-fat diet (HFD)-induced obese mice. FC notably increased the levels of glycerol in the culture supernatants and markedly reduced lipid accumulation in 3T3-L1 adipocytes. FC differentially inhibited the expressions of adipogenesis-related genes, including the peroxisome proliferator-activated receptor proteins, CCAAT/enhancer-binding proteins, and sterol regulatory element-binding proteins. FC markedly reduced the expressions of lipid synthesis-related genes, such as the fatty acid binding protein, lipoprotein lipase, and fatty acid synthase. Furthermore, FC significantly increased the expressions of lipolysis-related genes, such as the hormone-sensitive lipase, Aquaporin-7, and adipose triglyceride lipase. In HFD-induced obese mice, intraperitoneal injections of FC decreased both the body weight and visceral adipose tissue weight. FC administration significantly reduced lipid accumulation. Moreover, FC could dose-dependently and differentially regulate the expressions of lipid metabolism-related transcription factors. All these data indicated that FC exhibited anti-obesity effects through modulating adipogenesis and lipolysis.

Trp64Arg polymorphism of the ADRB3 gene associated with maximal fat oxidation and LDL-C levels in non-obese adolescents / Polimorfismo Trp64Arg do gene ADRB3 associado à oxidação máxima de gorduras e à concentração de LDL-c em adolescentes não obesos

Abstract Objective: To analyze the association between the Trp64Arg polymorphism of the ADRB3 gene, maximal fat oxidation rates and the lipid profile levels in non-obese adolescents. Methods: 72 schoolchildren, of both genders, aged between 11 and 17 years, participated in the study. The anthropometric and body composition variables, in addition to total cholesterol, HDL-c, LDL-c, triglycerides, insulin, and basal glycemia, were evaluated. The sample was divided into two groups according to the presence or absence of the polymorphism: non-carriers of the Arg64 allele, i.e., homozygous (Trp64Trp: n = 54), and carriers of the Arg64 allele (Trp64Arg + Arg64Arg: n = 18), in which the frequency of the Arg64 allele was 15.2%. The maximal oxygen uptake and peak of oxygen uptake during exercise were obtained through the symptom-limited, submaximal treadmill test. Maximal fat oxidation was determined according to the ventilatory ratio proposed in Lusk's table. Results: Adolescents carrying the less frequent allele (Trp64Arg and Arg64Arg) had higher LDL-c levels (p = 0.031) and lower maximal fat oxidation rates (p = 0.038) when compared with non-carriers (Trp64Trp). Conclusions: Although the physiological processes related to lipolysis and lipid metabolism are complex, the presence of the Arg 64 allele was associated with lower rates of FATMAX during aerobic exercise, as well as with higher levels of LDL-c in adolescents.

Resumo Objetivo: Analisar a associação entre o polimorfismo Trp64Arg do gene ADRB3, as taxas de oxidação máxima de gorduras e as concentrações do perfil lipídico em adolescentes não obesos. Métodos: Participaram do estudo 72 escolares, de ambos os sexos, com idade entre 11 e 17 anos. Foram avaliadas as variáveis antropométricas e de composição corporal, além do colesterol total, lipoproteina de alta densidade, lipoproteina de baixa densidade, triglicerídeos; insulina e glicemia basal. A amostra foi dividida em dois grupos, segundo a presença ou não do polimorfismo: não portadores do alelo Arg64, ou seja, homozigotos (Trp64Trp: n = 54) e portadores do alelo Arg64 (Trp64Arg + Arg64Arg: n = 18), em que a frequência do alelo Arg64 foide 15,2%. O consumo máximo de oxigênio e pico de consumo máximo de oxigênio durante o exercício foram obtidos por meio do teste aeróbio submáximo de sintoma limitado em esteira. A oxidação máxima de gorduras foi determinada de acordo com a razão de trocas ventilatórias propostas na Tabela de Lusk. Resultados: Os adolescentes portadores do alelo menos frequente (Trp64Arg e Arg64Arg) apresentaram maiores concentrações de lipoproteina de baixa densidade (p = 0,031) e menores taxasde oxidação máxima de gorduras (p = 0,038) quando comparados aos não portadores (Trp64Trp). Conclusões: Embora os processos fisiológicos relacionados à lipólise e ao metabolismo de lipídeos sejam complexos, a presença do alelo Arg64 associou-se a menores taxas de FATMAX durante exercício aeróbio, bem como maiores níveis de lipoproteina de baixa densidade em adolescentes.

Lipoaspiração laser-assistida de alta definição / High-definition laser-assisted lipoaspiration

Introdução: Desde a introdução da técnica de lipoaspiração, a melhora do contorno corporal vem ganhando novos horizontes. O uso da lipoaspiração superficial passou a ser usado a favor da estética e, com isso, o uso de tecnologias, tais como o VASER e o laser de Diodo, nos comprimentos de 915 e 980 nn, diminuem as complicações, com melhora da dor pós-operatória, tempo de cicatrização e retração cutânea. Métodos: Foram estudados, inicialmente, 16 pacientes submetidos à laserlipólise de alta definição, entre o período de 2014 e 2016. O nível de satisfação em relação ao resultado foi questionado aos pacientes. Resultados: A maioria dos pacientes foi do sexo masculino, idade média 39 anos, com média de dor de 2,3 de na escala de visual de dor (0 a 10), apresentando resultados duradouros após 1 ano, sem complicações e retorno às suas atividades de trabalho e físicas precocemente. Conclusões: Desta forma, o uso do laser de Diodo com comprimentos de ondas de 915 e 980 nm, associado à Lipoescultura de Alta Definição, promoveu resultados satisfatórios, promissores devendo ser testado numa amostragem maior de pacientes.

Introduction: Since the introduction of the liposuction technique, the improvement of body contour has been gaining new horizons. Superficial liposuction has been used in favor of aesthetics; the use of technologies, such as VASER and diode laser at 915- and 980-nm wavelengths, helps reduce complications and improves post-time, healing time, and cutaneous retraction. Methods: Fourteen patients submitted to high-resolution laser lipolysis were studied between 2014 and 2016. The level of patient satisfaction regarding the treatment outcome was assessed. Results: The majority of the patients were men, with a mean age of 39 years and a mean pain score of 2.3 on the visual pain scale (0 to 10), presenting lasting results after 1 year, with no complications and an early return to work and physical activities. Conclusions: The use of diode laser at the wavelengths of 915 and 980 nm in high-definition liposculpture promoted satisfactory, promising results and should be tested in a larger sample of patients.

Channel Function of TRPML1 Prompts Lipolysis in Mature Adipocytes

Increased intracellular levels of Ca²⁺ are generally thought to negatively regulate lipolysis in mature adipocytes, whereas store-operated Ca²⁺ entry was recently reported to facilitate lipolysis and attenuate lipotoxicity by inducing lipophagy. Transient receptor potential mucolipin1 (TRPML1), a Ca²⁺-permeable non-selective cation channel, is mainly expressed on the lysosomal membrane and plays key roles in lysosomal homeostasis and membrane trafficking. However, the roles of TRPML1 in lipolysis remains unclear. In this study, we examined whether the channel function of TRPML1 induces lipolysis in mature adipocytes. We found that treatment of mature adipocytes with ML-SA1, a specific agonist of TRPML1, solely upregulated extracellular glycerol release, but not to the same extent as isoproterenol. In addition, knockdown of TRPML1 in mature adipocytes significantly reduced autophagic flux, regardless of ML-SA1 treatment. Our findings demonstrate that the channel function of TRPML1 partially contributes to lipid metabolism and autophagic membrane trafficking, suggesting that TRPML1, particularly the channel function of TRPML1, is as therapeutic target molecule for treating obesity.

Effect of Danhong injection on AMPK/SREBP-1/ACC pathways of liver in hyperlipidemic rats / 中国药理学通报

Aim To discuss the effect of Danhong in-jection(DHI) on hyperlipidemia in rats and its possible mechanism. Methods The hyperlipidemia model of rats were induced by high fat diet. The protein expres-sion of adenosine 5'-monophosphate-activated protein kinase(AMPK), p-AMPK, cholesterol-binding ele-ment binding protein (SREBP-1), adenylate-activated protein kinase carboxylasecetyl-CoA(ACC) and p-ACC in liver were detected using Western blot. Results The protein expression levels of AMPK, SREBP-1 and ACC significantly decreased (P<0.05), but the pro-tein expression levels of p-ACC and p-AMPK signifi-cantly increased (P<0.05). Conclusions Danhong injection can reduce the activity of SREBP-1 and ACC by enhancing the activation of AMPK, and effectively reduce the blood lipid level of hyperlipidemic rats by promoting fatty acid oxidation and reducing lipid depo-sition.